Design, synthesis, and biological activity of a novel series of benzofuran derivatives against oestrogen receptor-dependent breast cancer cell lines.
In conclusion, the novel benzofuran scaffold may be a promising lead for the development of potential oestrogen receptor inhibitors. PMID: 31935604 [PubMed - as supplied by publisher] (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - January 7, 2020 Category: Chemistry Authors: Jin LP, Xie Q, Huang EF, Wang L, Zhang BQ, Hu JS, Wan DC, Jin Z, Hu C Tags: Bioorg Chem Source Type: research

ent-Labdane and ent-kaurane diterpenoids from Chelonopsis odontochila with α-glucosidase inhibitory activity.
This study provides new insights for the antidiabetic effects of C. odontochila with ent-labdane and ent-kaurane diterpenoids as the active constituents. PMID: 31927318 [PubMed - as supplied by publisher] (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - January 7, 2020 Category: Chemistry Authors: Deng ZT, Chen JJ, Geng CA Tags: Bioorg Chem Source Type: research

Novel 3-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-1,2,4-oxadiazol-5(4H)-ones as promising xanthine oxidase inhibitors: Design, synthesis and biological evaluation.
In this study, a number of 3-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-1,2,4-oxadiazol-5(4H)-ones (3a-3w) were newly designed by a bioisosteric replacement and hybrid strategy with the hope of obtaining novel and effective nonpurine XO inhibitors. Subsequently, these compounds were synthesized through a three-step procedure, with good yields. In addition, the in vitro bovine XO inhibitions were measured by spectrophotometric determination of uric acid formation at 295 nm using allopurinol as a positive control. As a result, compound 3j was found to be the most potent XO inhibitor, with an IC50 value of 0.121 µ...
Source: Bioorganic Chemistry - December 31, 2019 Category: Chemistry Authors: Gao J, Zhang Z, Zhang B, Mao Q, Dai X, Zou Q, Lei Y, Feng Y, Wang S Tags: Bioorg Chem Source Type: research

Design, synthesis, biological evaluation and molecular docking studies of new chalcone derivatives containing diaryl ether moiety as potential anticancer agents and tubulin polymerization inhibitors.
Abstract A novel series of chalcone derivatives containing diaryl ether moiety (5a-5p) were designed, synthesized and evaluated their anti-tubulin polymerization activities and anticancer activities. Among them, compound 5b with 4-methoxy substitution on right aromatic ring was found to be most active on MCF-7, HepG2 and HCT116 cancer cell lines, with IC50 values of 3.44 ± 0.19, 4.64 ± 0.23, and 6.31 ± 0.27 μM, respectively. In vitro tubulin polymerization assay showed that 5b could effectively inhibit tubulin polymerization. Further mechanism studies reve...
Source: Bioorganic Chemistry - December 31, 2019 Category: Chemistry Authors: Wang G, Liu W, Gong Z, Huang Y, Li Y, Peng Z Tags: Bioorg Chem Source Type: research

Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonists.
Abstract STING (Stimulator of Interferon Genes) has become a focal point in immunology research and a target in drug discovery. The discovery of a potent human-STING agonist is expected to revolutionize current anti-virus or cancer immunotherapy. Inspired by the structure and function of murine STING-specific agonists (DMXAA and CMA), we rationally designed and synthesized four series of novel compounds for the enhancement of human sensitivity. In the cell-based assay, we identified six compounds from all the synthetic small molecules: 2g, 9g, and 12b are STING agonists that are efficacious across species, and all...
Source: Bioorganic Chemistry - December 30, 2019 Category: Chemistry Authors: Hou S, Lan XJ, Li W, Yan XL, Chang JJ, Yang XH, Sun W, Xiao JH, Li S Tags: Bioorg Chem Source Type: research

The in vitro cytotoxicity, antioxidant and antibacterial potential of Satureja hortensis L. essential oil cultivated in Egypt.
This study was designed to evaluate the antioxidant, antibacterial and cytotoxicity effects of Satureja hortensis (S. hortensis) essential oil (EO). The GC-MS analysis of S. hortensis EO (SEO) has identified seven compounds, representing 96.84% of the oil. The two main constituents of the oil were; carvacrol (48.51%) and γ-terpinene (36.63%). The total phenolics and flavonoids contents of SEO were 199.1 ± 0.5 µg GAE/mg (GAE-gallic acid equivalent) and 161.5 ± 0.9 µg CE/mg (CE-catechin equivalent), respectively. SEO showed superior antioxidant potential (ABTS, 10...
Source: Bioorganic Chemistry - December 29, 2019 Category: Chemistry Authors: Abou Baker DH, Al-Moghazy M, ElSayed AAA Tags: Bioorg Chem Source Type: research

Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors.
Abstract A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H &13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h &4g are potential antioxidants. The obtained in vitro results were compared with the molecul...
Source: Bioorganic Chemistry - December 29, 2019 Category: Chemistry Authors: Lachhi Reddy V, Avula VKR, Zyryanov GV, Vallela S, Anireddy JS, Pasupuleti VR, Chamarthi NR Tags: Bioorg Chem Source Type: research

Polyhydroxyl guaianolide terpenoids as potential NF- кB inhibitors induced cytotoxicity in human gastric adenocarcinoma cell line.
Polyhydroxyl guaianolide terpenoids as potential NF-кB inhibitors induced cytotoxicity in human gastric adenocarcinoma cell line. Bioorg Chem. 2019 Dec 28;95:103551 Authors: Sun YW, Ju Y, Liu CH, Du KC, Meng DL Abstract Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and...
Source: Bioorganic Chemistry - December 28, 2019 Category: Chemistry Authors: Sun YW, Ju Y, Liu CH, Du KC, Meng DL Tags: Bioorg Chem Source Type: research

Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors.
We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a-d, 7a-c and 10) as well as hydroxamic acid (15a-b), carboxylic acid (16a-b), carboxamide (17a-b) and boronic acid (22a-b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range o...
Source: Bioorganic Chemistry - December 28, 2019 Category: Chemistry Authors: Uslu AG, Gür Maz T, Nocentini A, Banoglu E, Supuran CT, Çalışkan B Tags: Bioorg Chem Source Type: research

Development of novel carbazole derivatives with effective multifunctional action against Alzheimer's diseases: Design, synthesis, in silico, in vitro and in vivo investigation.
Abstract Carbazole based novel multifunctional agents has been rationally designed and synthesized as potential anti-Alzheimer agents. Multi-functional activity of these derivatives have been assessed by performing various in-vitro assays and these compounds appeared to be potent AChE inhibitors, Aβ aggregation inhibitors, anti-oxidant and neuroprotective agents. Among the entire series, MT-1 and MT-6 were most potent multifunctional agents which displayed effective and selective AChE inhibition, Aβ disaggregation, anti-oxidant and metal chelation action. Neuroprotective activity of MT-6 has been examine...
Source: Bioorganic Chemistry - December 28, 2019 Category: Chemistry Authors: Mishra CB, Gusain S, Shalini S, Kumari S, Prakash A, Kumari N, Yadav AK, Kumari J, Kumar K, Tiwari M Tags: Bioorg Chem Source Type: research

New antifungal ent-labdane diterpenes against Candida glabrata produced by microbial transformation of ent-polyalthic acid.
Abstract Candida glabrata, the most common non-albicans Candida species and one of the primary causes of candidemia, exhibits decreased susceptibility to azoles and more recently to echinocandins. Polyalthic acid 1, a furan diterpene, has been shown promising biological potential and in this study ent-polyalthic acid derivatives with antifungal activity against Candida glabrata were produced by microbial transformation. Incubation of 1 with Aspergillus brasiliensis afforded two known (compounds 5 and 10) and eight new derivatives (compounds 2-4, 6-9 and 11). The most common reaction was hydroxylation, but isomeriz...
Source: Bioorganic Chemistry - December 28, 2019 Category: Chemistry Authors: Pontes de Sousa I, Ferreira AG, Miller Crotti AE, Alves Dos Santos R, Kiermaier J, Kraus B, Heilmann J, Jacometti Cardoso Furtado NA Tags: Bioorg Chem Source Type: research

Structure-activity relationship of human carbonic anhydrase-II inhibitors: Detailed insight for future development as anti-glaucoma agents.
Abstract Human carbonic anhydrase-II (hCA-II) is the most dominant physiologic isoform amongst the sixteen reported hCA isoforms. Because of its high availability in the different anatomical, and cellular sites of the eye like retina and lens, it plays a more prominent role in the regulation of intraocular pressure than the other twelve catalytically active hCA isoforms. This isoform is also located in the brain, kidney, gastric mucosa, osteoclasts, RBCs, skeletal muscle, testes, pancreas, lungs, etc. Earlier, hCA-II inhibitors were designed based on the sulfonamides e.g. acetazolamide, dichlorphenamide, methazola...
Source: Bioorganic Chemistry - December 27, 2019 Category: Chemistry Authors: Ghorai S, Pulya S, Ghosh K, Panda P, Ghosh B, Gayen S Tags: Bioorg Chem Source Type: research

Synthesis, α-glycosidase inhibitory potential and molecular docking study of benzimidazole derivatives.
Synthesis, α-glycosidase inhibitory potential and molecular docking study of benzimidazole derivatives. Bioorg Chem. 2019 Dec 26;95:103555 Authors: Taha M, Rahim F, Zaman K, Selvaraj M, Uddin N, Farooq RK, Nawaz M, Sajid M, Nawaz F, Ibrahim M, Khan KM Abstract A series of twenty-six analogs of benzimidazole based oxadiazole have been synthesized and evaluated against alpha-glycosidase enzyme. Most the analogs showed excellent to good inhibitory potential. Among the screened analogs, analog 1, 2, 3 and 14 with IC50 values 4.6 ± 0.1, 9.50 ± 0.3, 2.6 ±&...
Source: Bioorganic Chemistry - December 26, 2019 Category: Chemistry Authors: Taha M, Rahim F, Zaman K, Selvaraj M, Uddin N, Farooq RK, Nawaz M, Sajid M, Nawaz F, Ibrahim M, Khan KM Tags: Bioorg Chem Source Type: research

Design, synthesis, docking and biological evaluation of chalcones as promising antidiabetic agents.
In this study, amino chalcones (3a-j) were synthesized and hydroxy chalcones (3g-j) were isolated from natural source such as Sophora interrupta, Clerodendrum phlomidis and Andrographis macrobotrys. Structural elucidation was carried out using Mass, 1H and 13C NMR Spectra. In vivo studies were carried out with alloxan induced diabetic rats (100 mg/kg) which reveals compounds 3c, 3a and 3h have significant antidiabetic efficacy with decreased blood glucose levels in the diabetic rats while compared with control rats. Besides, docking studies with aldose reductase, dipeptidyl peptidase, PPAR and glucosidase were monitor...
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Rammohan A, Bhaskar BV, Venkateswarlu N, Gu W, Zyryanov GV Tags: Bioorg Chem Source Type: research

Chemistry, structure, and biological roles of Au-NHC complexes as TrxR inhibitors.
Ateş B Abstract In recent years, the preparation of metal complexes and the introduction of biologically active organometalic compounds are new strategies in drug development. For this purpose, generally N-heterocyclic pharmaceutical agents have been used as promising nuclei. Au-containing N-heterocyclic carbene (Au-NHC) derivatives are among the compounds used for this purpose, and their enzyme inhibition, antioxidant activity, antimicrobial and anticancer properties are widely studied. In these studies, the anticancer property of Au-NHC complexes is the most widely studied area. The common result in different s...
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Karaaslan MG, Aktaş A, Gürses C, Gök Y, Ateş B Tags: Bioorg Chem Source Type: research

( ±)-Kituramides A and B, pairs of enantiomeric dopamine dimers from the two-spotted cricket Gryllus bimaculatus.
(±)-Kituramides A and B, pairs of enantiomeric dopamine dimers from the two-spotted cricket Gryllus bimaculatus. Bioorg Chem. 2019 Dec 24;95:103554 Authors: Lee SR, Yi SA, Nam KH, Park JG, Hwang JS, Lee J, Kim KH Abstract Two-spotted cricket Gryllus bimaculatus is one of many cricket species, and it is widely used as a food source for insectivorous animals. Moreover, this species is one of the edible insects approved by the Korea Food and Drug Administration (KFDA). (±)-Kituramides A (1) and B (2), which are pairs of novel enantiomeric dopamine dimers possessing a formamide group, were i...
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Lee SR, Yi SA, Nam KH, Park JG, Hwang JS, Lee J, Kim KH Tags: Bioorg Chem Source Type: research

Design and optimization of orally spleen tyrosine kinase (SYK) inhibitors for treatment of solid tumor.
Abstract As the aim to discover orally SYK inhibitors for solid tumor treatment, a series of novel derivatives based on imidazo[1,2-a]pyrazine scaffold were designed, synthesized and evaluated. Structure-activity relationship study of both enzymatic and cellular assays led to the identification of compound 12f. The novel SYK inhibitor 12f showed potent antitumor activity against solid tumors with favorable drug-like properties of lipophilicity and solubility. 12f could induce cell apoptosis of ovarian and lung cancer cell lines. In SKOV3 xenograft mouse model, oral administration of 12f led to significant tumour r...
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Wang C, Wang X, Li Y, Wang T, Huang Z, Qin Z, Yang S, Xiang R, Fan Y Tags: Bioorg Chem Source Type: research

JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma.
In this study, a new class of thieno[3,2-d]pyrimidines harboring acrylamide pharmacophore were synthesized as potent covalent JAK3 inhibitors (IC50 
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Chi F, Chen L, Wang C, Li L, Sun X, Xu Y, Ma T, Liu K, Ma X, Shu X Tags: Bioorg Chem Source Type: research

Design and synthesis of novel cylopentapyrazoles bearing 1,2,3-thiadiazole moiety as potent antifungal agents.
In this study, a novel series of cylopentapyrazole bearing a 1,2,3-thiadiazole ring 2a-e were designed and synthesized according to the principle of combination of bioactive structures. Thus, we have employed a [3 + 2] cycloaddition with 4-methyl-[1,2,3] thiadiazole-5-carboxylic acid hydrazones 1a-e and cyclopentadiene ring. Novel synthesized compounds were identified with IR, 1H and 13C NMR, mass spectrometry and elemental analysis then, antifungal activities were assayed. Based on our study, a combination of the compounds 1a and 2b possess remarkable antifungal activity against Botrytis cinerea AHU 9424 with 10...
Source: Bioorganic Chemistry - December 24, 2019 Category: Chemistry Authors: Giray B, Karadağ AE, İpek ÖŞ, Pekel H, Güzel M, Küçük HB Tags: Bioorg Chem Source Type: research

New potential drug leads against MDR-MTB: A short review.
Abstract Multidrug resistant Mycobacterium tuberculosis (MDR-MTB) infections have created a critical health problem globally. The appalling rise in drug resistance to all the current therapeutics has triggered the need for identifying new antimycobacterial agents effective against multidrug-resistant Mycobacterium tuberculosis. Structurally unique chemical entities with new mode of action will be required to combat this pressing issue. This review gives an overview of the structures and outlines on various aspects of in vitro pharmacological activities of new antimycobacterial agents, mechanism of action and brief...
Source: Bioorganic Chemistry - December 23, 2019 Category: Chemistry Authors: Gatadi S, Nanduri S Tags: Bioorg Chem Source Type: research

Design and synthesis of newer 1,3,4-oxadiazole and 1,2,4-triazole based Topsentin analogues as anti-proliferative agent targeting tubulin.
Abstract A set of two series of 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were prepared by replacing imizadole moiety of topsentin through a multistep synthesis starting from indole. All the compounds synthesized were submitted for single dose (10 µM) screening against a NCI panel of 60-human cancer cell lines. Among all cancer cell lines, colon (HCC-2998) and Breast (MCF-7, T-47D) cancer cell lines were found to be more susceptible for this class of compounds. Among the compounds tested, compounds 11a, 11d, 11f, 12e and 12h, were exhibited good anti-pr...
Source: Bioorganic Chemistry - December 23, 2019 Category: Chemistry Authors: Naaz F, Ahmad F, Lone BA, Pokharel YR, Fuloria NK, Fuloria S, Ravichandran M, Pattabhiraman L, Shafi S, Shahar Yar M Tags: Bioorg Chem Source Type: research

Green synthesis and biological evaluation of 6-substituted-2-(2-hydroxy/methoxy phenyl)benzothiazole derivatives as potential antioxidant, antibacterial and antitumor agents.
We present a new efficient green synthetic protocol for introduction of substituents to the C-6 position of 2-arylbenzothiazole nuclei. Newly synthesized compounds were designed to study the influence of the hydroxy and methoxy groups on the 2-arylbenzothiazole scaffold, as well as the influence of the type of substituents placed on the C-6 position of benzothiazole moiety on biological activity, including antibacterial, antitumor and antioxidant activity. Modest activity was observed against the tested Gram-positive and Gram-negative bacterial strains for only amidino derivatives 5d and 6d. The tested compounds exhibited ...
Source: Bioorganic Chemistry - December 23, 2019 Category: Chemistry Authors: Racané L, Ptiček L, Fajdetić G, Tralić-Kulenović V, Klobučar M, Kraljević Pavelić S, Perić M, Paljetak HČ, Verbanac D, Starčević K Tags: Bioorg Chem Source Type: research

Synthesis and selective inhibitory effects of some 2-oxindole benzenesulfonamide conjugates on human carbonic anhydrase isoforms CA I, CA II, CA IX and CAXII.
Abstract Three series of 2-oxindole benzenesulfonamide conjugates with different linkers were prepared by the condensation reaction of isatin derivatives 1a-e with different benzenesulfonamides. They were screened for their ability to inhibit human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX and hCA XII. Many compounds revealed promising activity and selectivity toward CAI, CAII and CAIX compared to acetazolamide (AAZ) especially compounds 2b (KI = 97.6, 8.0 nM against hCA I, hCA II, respectively) and 3a (KI = 90.2, 6.5 and 21.4 nM against hCA I, hCA II and ...
Source: Bioorganic Chemistry - December 23, 2019 Category: Chemistry Authors: George RF, Said MF, Bua S, Supuran CT Tags: Bioorg Chem Source Type: research

A proficient microwave synthesis with structure elucidation and the exploitation of the biological behavior of the newly halogenated 3-amino-1H-benzo[f]chromene molecules, targeting dual inhibition of topoisomerase II and microtubules.
This study also revealed that the desired compounds stimulate cell cycle arrest at the G2/M phases, increase the production of Caspases 3, 8, and 9, and finally cause intrinsic and extrinsic apoptotic cell death. Moreover, these compounds suppress the action of the topoisomerase II enzyme and also disrupt the microtubule functions. The SAR study of the synthesized compounds verified that the substitution on the phenyl ring of the 1H-benzo[f]chromene nucleus, accompanied with the presence of the bromine atom at the 8-position, increases the ability of these molecules against different cell lines. PMID: 31887476 [PubMed...
Source: Bioorganic Chemistry - December 23, 2019 Category: Chemistry Authors: Fouda AM, Okasha RM, Alblewi FF, Mora A, Afifi TH, El-Agrody AM Tags: Bioorg Chem Source Type: research

Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety.
CONCLUSION: We suggest that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency. PMID: 31884144 [PubMed - as supplied by publisher] (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - December 21, 2019 Category: Chemistry Authors: Berczyński P, Kładna A, Bozdağ Dündar O, Murat HN, Sarı E, Kruk I, Aboul-Enein HY Tags: Bioorg Chem Source Type: research

Design, synthesis and bioactivity evaluation of coumarin-chalcone hybrids as potential anticancer agents.
Abstract The selenoprotein thioredoxin reductases (TrxRs) have been extensively studied as a potential target for the development of anticancer drugs. Herein, we designed, synthesized, and evaluated a series of coumarin-chalcone hybrids as TrxR inhibitors. Most of them exhibited enhancing anticancer activity than Xanthohumol (Xn). The representative Xn-2 (IC50 = 3.6 μM) was a fluorescence agent, wherein drug uptake can be readily monitored in living cells by red fluorescence imaging. Xn-2 down-regulated the expression of TrxR, remarkedly induced ROS accumulation to activate mitochondrial apoptosi...
Source: Bioorganic Chemistry - December 21, 2019 Category: Chemistry Authors: Wang Y, Zhang W, Dong J, Gao J Tags: Bioorg Chem Source Type: research

Novel N,N-dimethylbarbituric-pyridinium derivatives as potent urease inhibitors: Synthesis, in vitro, and in silico studies.
Abstract A new series of N,N-dimethylbarbituric-pyridinium derivatives 7a-n was synthesized and evaluated as Helicobacter pylori urease inhibitors. All the synthesized compounds (IC50 = 10.37 ± 1.0-77.52 ± 2.7 μM) were more potent than standard inhibitor hydroxyurea against urease (IC50 = 100.00 ± 0.2 μM). Furthermore, comparison of IC50 values of the synthesized compounds with the second standard inhibitor thiourea (IC50 = 22.0 ± 0.03 µM) revealed that compounds 7a-b and 7f-h were more pote...
Source: Bioorganic Chemistry - December 20, 2019 Category: Chemistry Authors: Biglar M, Mirzazadeh R, Asadi M, Sepehri S, Valizadeh Y, Sarrafi Y, Amanlou M, Larijani B, Mohammadi-Khanaposhtani M, Mahdavi M Tags: Bioorg Chem Source Type: research

Design, synthesis and biological evaluation of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as potential dual PI3K α/mTOR inhibitors.
Design, synthesis and biological evaluation of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as potential dual PI3Kα/mTOR inhibitors. Bioorg Chem. 2019 Dec 20;95:103525 Authors: Zhang B, Zhang Q, Xiao Z, Sun X, Yang Z, Gu Q, Liu Z, Xie T, Jin Q, Zheng P, Xu S, Zhu W Abstract The phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been regarded as promising targets for the treatment of cancer. Herein, we synthesized a new series of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as novel PI3Kα/mTOR dual inhibitors for cancer therapy. All compou...
Source: Bioorganic Chemistry - December 20, 2019 Category: Chemistry Authors: Zhang B, Zhang Q, Xiao Z, Sun X, Yang Z, Gu Q, Liu Z, Xie T, Jin Q, Zheng P, Xu S, Zhu W Tags: Bioorg Chem Source Type: research

Synthesis, molecular docking and biological evaluation of 2-(thiophen-2-yl)-1H-indoles as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
Abstract New 2-(thiophen-2-yl)-1H-indole derivatives bearing hydrophobic substituents at the 3-position were designed, synthesized and evaluated for their inhibition of HIV-1 reverse transcriptase (RT) enzyme. Dialkylphosphites (2a-c) or trialkylphosphites (3a-c) were reacted with 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde (1) yielding the corresponding α-hydroxyphosphonate adducts (7a-7c). The reaction of compound 1 with the ylidenetriphenylphosphoranes (4a-4c) proceeds via Wittig mechanism giving the corresponding ethylenes (E, 8a-c). Compounds 8b,c were equally obtained upon reacting aldehyde 1 with the a...
Source: Bioorganic Chemistry - December 19, 2019 Category: Chemistry Authors: El-Hussieny M, El-Sayed NF, Ewies EF, Ibrahim NM, Mahran MRH, Fouad MA Tags: Bioorg Chem Source Type: research

Anti-Trypanosoma cruzi activity of costic acid isolated from Nectandra barbellata (Lauraceae) is associated with alterations in plasma membrane electric and mitochondrial membrane potentials.
Abstract As part of our continuous studies on prospecting metabolites from Brazilian plant species with pharmacologic activity against Trypanosoma cruzi, the n-hexane extract from twigs of Nectandra barbellata (Lauraceae) was subjected to a bioactivity-guided fractionation to afford the sesquiterpene costic acid. As results, costic acid induced a trypanocidal effect with IC50 of 37.8 and 7.9 μM to trypomastigotes and intracellular amastigotes, respectively. When tested in L929 cells, no cytotoxicity was detected in the highest tested concentration (CC50 > 200 μM), resulting in SI value...
Source: Bioorganic Chemistry - December 18, 2019 Category: Chemistry Authors: Londero VS, Costa-Silva TA, Tempone AG, Namiyama GM, Thevenard F, Antar GM, Baitello JB, Lago JHG Tags: Bioorg Chem Source Type: research

Design, synthesis and biological evaluation of new embelin derivatives as CK2 inhibitors.
acute;vez-Braun A Abstract A new series of furan embelin derivatives was synthesized and characterized as ATP-competitive CK2 inhibitors. The new compounds were efficiently synthesized using a multicomponent approach from embelin (1), aldehydes and isonitriles through a Knoevenagel condensation/Michael addition/heterocyclization. Several compounds with inhibitory activities in the low micromolar or even submicromolar were identified. The most active derivative was compound 4l (2-(tert-butylamino)-3-(furan-3-yl)-5-hydroxy-6-undecylbenzofuran-4,7-dione) with an IC50 value of 0.63 μM. It turned out to be an A...
Source: Bioorganic Chemistry - December 18, 2019 Category: Chemistry Authors: Oramas-Royo S, Haidar S, Amesty Á, Martín-Acosta P, Feresin G, Tapia A, Aichele D, Jose J, Estévez-Braun A Tags: Bioorg Chem Source Type: research

Synthesis, in vitro biological evaluation and in silico molecular docking studies of novel β-lactam-anthraquinone hybrids.
Synthesis, in vitro biological evaluation and in silico molecular docking studies of novel β-lactam-anthraquinone hybrids. Bioorg Chem. 2019 Dec 17;95:103515 Authors: Mohamadzadeh M, Zarei M, Vessal M Abstract Schiff bases from 2-aminoanthraquinone have been prepared by reaction with aldehydes and used to prepare novel β-lactam-anthraquinone hybrids via [2+2] ketene-imine cycloaddition (Staudinger reaction) reaction. In vitro antibacterial studies of all synthesized compound were carried out against three gram-positive strains Staphylococcus aureus (Methicillin-resistant strain), Enterococcu...
Source: Bioorganic Chemistry - December 17, 2019 Category: Chemistry Authors: Mohamadzadeh M, Zarei M, Vessal M Tags: Bioorg Chem Source Type: research

The anti-inflammatory effects of jiangrines from Jiangella alba through inhibition of p38 and NF- κB signaling pathways.
The anti-inflammatory effects of jiangrines from Jiangella alba through inhibition of p38 and NF-κB signaling pathways. Bioorg Chem. 2019 Dec 17;95:103507 Authors: Guan P, Wang X, Jiang Y, Dou N, Qu X, Liu J, Lin B, Han L, Huang X, Jiang C Abstract Three pyrrol-2-aldehyde derivatives, including one new compound, jiangrine G (JG), two known compounds, jiangrine A (JA), and pyrrolezanthine (PZ), were isolated from the fermentation broth of Jiangella alba associated with a traditional Chinese medicinal plant Maytenus austroyunnanensis. The structure of jiangrine G was elucidated by a detailed spect...
Source: Bioorganic Chemistry - December 17, 2019 Category: Chemistry Authors: Guan P, Wang X, Jiang Y, Dou N, Qu X, Liu J, Lin B, Han L, Huang X, Jiang C Tags: Bioorg Chem Source Type: research

Synthesis and antimicrobial evaluation of new halogenated 1,3-Thiazolidin-4-ones.
In this study, two series of halogenated 1,3-thiazolidin-4-ones were synthesized and characterized. All the synthesized thiazolidinone derivatives were evaluated for their antimicrobial activity. Biological screening of the tested compounds revealed the antibacterial activity of the chlorinated thiazolidinones 4a, 4b and 4c against Escherichia coli TolC-mutant, with MIC values of 16 µg/mL. A combination of a sub-inhibitory concentration of colistin (0.25 × MIC) with compounds 4a, 4b or 4c showed antibacterial activity against different Gram-negative bacteria (MICs = 4-16 µg/m...
Source: Bioorganic Chemistry - December 17, 2019 Category: Chemistry Authors: Hammad SG, El-Gazzar MG, Abutaleb NS, Li D, Ramming I, Shekhar A, Abdel-Halim M, Elrazaz EZ, Seleem MN, Bilitewski U, Abouzid KAM, El-Hossary EM Tags: Bioorg Chem Source Type: research

Andrographolide: Chemical modification and its effect on biological activities.
Abstract The major natural bioactive constituent of Andrographis paniculata (AP) (Burm. f.) Nees Andrographolide (1) and its derivatives are well acknowledged in literature for its biological activities such as anti-cancer, anti-diabetic, anti-inflammatory, anti-bacterial, anti-malarial, antihepatitis, anti-HIV, anti-atherosclerosis, hepatoprotective, FXR antagonist, and α-glucosidase inhibition. Many reports are available related to Andrographolide (1) but a consolidated review on the chemical modification of andrographolide with special emphasis on its different functional groups with respect to their biol...
Source: Bioorganic Chemistry - December 17, 2019 Category: Chemistry Authors: Kumar G, Singh D, Tali JA, Dheer D, Shankar R Tags: Bioorg Chem Source Type: research

Design, synthesis, and biological evaluation of ferulic acid based 1,3,4-oxadiazole hybrids as multifunctional therapeutics for the treatment of Alzheimer's disease.
Abstract Thirty ferulic acid-based 1,3,4-oxadiazole molecular hybrids were designed, synthesized, and screened them for multifunctional inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-secretase-1 (BACE-1). Compound 6j was the most potent inhibitor of AChE (IC50 = 0.068 µM). It also showed equipotent inhibition of BChE and BACE-1 with IC50 values of 0.218 µM and 0.255 µM, respectively. Compound 6k possessed the most significant inhibition of BChE and BACE-1 with IC50 values, 0.163 µM and 0.211 µM, respec...
Source: Bioorganic Chemistry - December 17, 2019 Category: Chemistry Authors: Tripathi A, Choubey PK, Sharma P, Seth A, Saraf P, Shrivastava SK Tags: Bioorg Chem Source Type: research

Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro.
Abstract In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices. Thus, we set out to develop innovative peptide dendrimers for clinical application as transfection agents and gene carriers...
Source: Bioorganic Chemistry - December 11, 2019 Category: Chemistry Authors: Gorzkiewicz M, Konopka M, Janaszewska A, Tarasenko II, Sheveleva NN, Gajek A, Neelov IM, Klajnert-Maculewicz B Tags: Bioorg Chem Source Type: research

Protoilludane-type sesquiterpenoids from Armillaria sp. by co-culture with the endophytic fungus Epicoccumsp. associated with Gastrodia elata.
Abstract An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compou...
Source: Bioorganic Chemistry - December 10, 2019 Category: Chemistry Authors: Li HT, Tang LH, Liu T, Yang RN, Yang YB, Zhou H, Ding ZT Tags: Bioorg Chem Source Type: research

Synthesis and biological evaluation of berberine derivatives as a new class of broad-spectrum antiviral agents against Coxsackievirus B.
Abstract A series of novel berberine (BBR) analogues were prepared and tested for their antiviral potencies against six different genotype Coxsackievirus B (CVB1-6) strains, taking BBR core for structural modification. Structure-activity relationship (SAR) research revealed that introduction of a primary amine through a linker at position 3 might be beneficial for both antiviral activity and safety. Compound 14c displayed most promising inhibitory potency with IC50 values of 3.08-9.94 µM against tested CVBs 2-6 strains and satisfactory SI value of 34.3 on CVB3, better than that of BBR. Also, 14c could i...
Source: Bioorganic Chemistry - December 9, 2019 Category: Chemistry Authors: Zeng QX, Wang HQ, Wei W, Guo TT, Yu L, Wang YX, Li YH, Song DQ Tags: Bioorg Chem Source Type: research

Steroid sulfatase inhibiting lanostane triterpenes - Structure activity relationship and in silico insights.
In this study, three ligand-based pharmacophore models were developed to identify STS inhibitors from natural sources. In a pharmacophore-based virtual screening of a curated molecular TCM database, lanostane-type triterpenes (LTTs) were predicted as STS ligands. Three traditionally used polypores rich in LTTs, i.e., Ganoderma lucidum Karst., Gloeophyllum odoratum Imazeki, and Fomitopsis pinicola Karst., were selected as starting materials. Based on eighteen thereof isolated LTTs a structure activity relationship for this compound class was established with piptolinic acid D (1), pinicolic acid B (2), and ganoderol A (3) b...
Source: Bioorganic Chemistry - December 9, 2019 Category: Chemistry Authors: Grienke U, Kaserer T, Kirchweger B, Lambrinidis G, Kandel RT, Foster PA, Schuster D, Mikros E, Rollinger JM Tags: Bioorg Chem Source Type: research

First triclosan-based macrocyclic inhibitors of InhA enzyme.
Abstract Two macrocyclic derivatives based on the triclosan frame were designed and synthesized as inhibitors of Mycobacterium tuberculosis InhA enzyme. One of the two molecules M02 displayed promising inhibitory activity against InhA enzyme with an IC50 of 4.7 μM. Molecular docking studies of these two compounds were performed and confirmed that M02 was more efficient as inhibitor of InhA activity. These molecules are the first macrocyclic direct inhibitors of InhA enzyme able to bind into the substrate pocket. Furthermore, these biaryl ether compounds exhibited antitubercular activities comparable to tha...
Source: Bioorganic Chemistry - December 6, 2019 Category: Chemistry Authors: Rodriguez F, Saffon N, Sammartino JC, Degiacomi G, Pasca MR, Lherbet C Tags: Bioorg Chem Source Type: research

Design, synthesis and evaluation of the antibacterial activity of new Linezolid dipeptide-type analogues.
Franco JL, Laniado-Laborín R Abstract Worldwide studies towards development of new drugs with a lower rate in emergence of bacterial resistance have been conducted. The molecular docking analysis gives a possibility to predict the activity of new compounds before to perform their synthesis. In this work, the molecular docking analysis of 64 Linezolid dipeptide-type analogues was performed to predict their activity. The most negative scores correspond to six Fmoc-protected analogues (9as, 9bs, 9bu, 10as, 10ax and 10ay) where Fmoc group interacts in PTC for Linezolid. Twenty-six different Fmoc-protected Linez...
Source: Bioorganic Chemistry - December 6, 2019 Category: Chemistry Authors: García-Olaiz GD, Alcántar-Zavala E, Ochoa-Terán A, Cabrera A, Muñiz-Salazar R, Montes-Ávila J, Salazar-Medina AJ, Alday E, Velazquez C, Medina-Franco JL, Laniado-Laborín R Tags: Bioorg Chem Source Type: research

New phosphazine and phosphazide derivatives as multifunctional ligands targeting acetylcholinesterase and β-Amyloid aggregation for treatment of Alzheimer's disease.
New phosphazine and phosphazide derivatives as multifunctional ligands targeting acetylcholinesterase and β-Amyloid aggregation for treatment of Alzheimer's disease. Bioorg Chem. 2019 Dec 06;95:103499 Authors: El-Sayed NF, El-Hussieny M, Ewies EF, Fouad MA, Boulos LS Abstract Phosphazine and phosphazide derivatives are described herein as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and β-amyloid aggregation inhibitors. Phosphazines (5-7) were synthesized smoothly via a redox-condensation reaction of 1,2-bis(diphenylphosphino)ethane with different amines derivat...
Source: Bioorganic Chemistry - December 6, 2019 Category: Chemistry Authors: El-Sayed NF, El-Hussieny M, Ewies EF, Fouad MA, Boulos LS Tags: Bioorg Chem Source Type: research

New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation.
Abstract New pyridazinone and pyridazinthione derivatives were designed, synthesized and identified through performing 1H NMR, 13C NMR, IR and MS spectroscopic techniques. All the newly synthesized derivatives were evaluated for cyclooxygenase inhibitory activity and COX-2 selectivity using celecoxib and indomethacin, as reference drugs. All compounds showed highly potent COX-2 inhibitory activity with IC50 values in nano-molar range. Moreover, they demonstrated higher selectivity towards COX-2 inhibition compared to indomethacin. Compounds 3d, 3g and 6a exhibited significantly increased potency towards COX-2 enzy...
Source: Bioorganic Chemistry - December 6, 2019 Category: Chemistry Authors: Ahmed EM, Hassan MSA, El-Malah AA, Kassab AE Tags: Bioorg Chem Source Type: research

Apoptosis: A target for anticancer therapy with novel cyanopyridines.
Abstract One of the many methods of treating cancer is to terminate the uncontrolled growth of cancer cells. So, aiming the apoptotic pathway is an exciting approach to finding new anticancer agents. A novel series of cyanopyridines was designed and synthesized for antiproliferative evaluation. 2-Amino-6-(4-(benzyloxy)phenyl)-4-(4-(dimethylamino)phenyl) nicotinonitrile 10f was the most potent inhibitor against the growth of PC-3, and HepG-2 cancer cell lines with IC50 values of 2.04 uM (selectivity index, SI = 78.63, 43, respectively). Also, 10f was safe against the growth of normal human diploid lung fi...
Source: Bioorganic Chemistry - December 5, 2019 Category: Chemistry Authors: Ismail MMF, Farrag AM, Harras MF, Ibrahim MH, Mehany ABM Tags: Bioorg Chem Source Type: research

Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors.
In this study, a series of benzimidazole-1,2,3-triazole hybrids 8a-n as new α-glucosidase inhibitors were designed and synthesized. In vitro α-glucosidase inhibition activity results indicated that all the synthesized compounds (IC50 values ranging from 25.2 ± 0.9 to 176.5 ± 6.7 μM) exhibited more inhibitory activity in comparison to standard drug acarbose (IC50 = 750.0 ± 12.5 μM). Enzyme kinetic study on the most potent compound 8c revealed that this compound was a competitive inhibitor into α-glucosidase. Moreover, the docking ...
Source: Bioorganic Chemistry - December 4, 2019 Category: Chemistry Authors: Asemanipoor N, Mohammadi-Khanaposhtani M, Moradi S, Vahidi M, Asadi M, Faramarzi MA, Mahdavi M, Biglar M, Larijani B, Hamedifar H, Hajimiri MH Tags: Bioorg Chem Source Type: research

Protective effects of polydatin on multiple organ ischemia-reperfusion injury.
In this study, we aim to review the protective mechanism of PD in the ischemia-reperfusion injury of various organs, and provide inspiration for future studies. PMID: 31836186 [PubMed - as supplied by publisher] (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - December 4, 2019 Category: Chemistry Authors: Sun Z, Wang X Tags: Bioorg Chem Source Type: research

Synthesis and antibacterial evaluation against resistant Gram-negative bacteria of monobactams bearing various substituents on oxime residue.
Abstract Based on the structural characteristics of aztreonam (AZN) and its target PBP3, a series of new monobactam derivatives bearing various substituents on oxime residue were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative bacteria. Among them, compounds 8p and 8r displayed moderate potency with MIC values of 0.125-32 μg/mL against most tested Gram-negative strains, comparable to AZN. Meanwhile, the combination of 8p and 8r with avibactam as a β-lactamases inhibitor, in a ratio of 1:16, showed a promising synergistic effect against both ESB...
Source: Bioorganic Chemistry - December 2, 2019 Category: Chemistry Authors: Li ZW, Lu X, Wang YX, Hu XX, Fu HG, Gao LM, You XF, Tang S, Song DQ Tags: Bioorg Chem Source Type: research

Prospective computational design and in vitro bio-analytical tests of new chemical entities as potential selective CYP17A1 lyase inhibitors.
Abstract The development and advancement of prostate cancer (PCa) into stage 4, where it metastasize, is a major problem mostly in elder males. The growth of PCa cells is stirred up by androgens and androgen receptor (AR). Therefore, therapeutic strategies such as blocking androgens synthesis and inhibiting AR binding have been explored in recent years. However, recently approved drugs (or in clinical phase) failed in improving the expected survival rates for this metastatic-castration resistant prostate cancer (mCRPC) patients. The selective CYP17A1 inhibition of 17,20-lyase route has emerged as a novel strategy....
Source: Bioorganic Chemistry - December 2, 2019 Category: Chemistry Authors: Gumede NJ, Nxumalo W, Bisetty K, Escuder Gilabert L, Medina-Hernandez MJ, Sagrado S Tags: Bioorg Chem Source Type: research

Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors.
Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors. Bioorg Chem. 2019 Dec 02;:103491 Authors: Aispuro-Pérez A, López-Ávalos J, García-Páez F, Montes-Avila J, Picos-Corrales LA, Ochoa-Terán A, Bastidas P, Montaño S, Calderón-Zamora L, Osuna-Martínez U, Sarmiento-Sánchez JI Abstract Imine functionality is found in many compounds with important biological activity. Thus, the development of novel synthetic approaches for imines is important. In this work, it is propose an easy, eco-fr...
Source: Bioorganic Chemistry - December 2, 2019 Category: Chemistry Authors: Aispuro-Pérez A, López-Ávalos J, García-Páez F, Montes-Avila J, Picos-Corrales LA, Ochoa-Terán A, Bastidas P, Montaño S, Calderón-Zamora L, Osuna-Martínez U, Sarmiento-Sánchez JI Tags: Bioorg Chem Source Type: research