Design, synthesis and biological evaluation of quinoxaline N -propionic and O -propionic hydrazide derivatives as antibacterial and antifungal agents
AbstractNovel series of quinaxoline derivatives incorporatingN-propionic andO-propionic hydrazide moieties were synthesized. Alkylation of 3-methylquinoxalin-2(1H)-one with ethyl 2-bromopropanoate afforded a mixture ofO-alkylated andN-alkylated 3-methylquinoxaline. Hydrazide derivatives were afforded by reaction ofO-alkylated andN-alkylated 3-methylquinoxaline with hydrazine hydrate. Condensation of hydrazide derivatives with different aromatic aldehydes and formylpyrazoles afforded the corresponding hydrazone derivatives. The synthesized quinaxoline derivatives were evaluated for their expected antimicrobial activity; whe...
Source: Medicinal Chemistry Research - August 17, 2018 Category: Chemistry Source Type: research

Activity evaluation of some psychoactive drugs with the application of QSAR/QSPR modeling methods
AbstractA set of psychoactive drugs has been analyzed with the use of quantitative structure –activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activi ty data and chromatographic retention parameters. During the study, the ab initio model of molecular modeling was performed and PCA, FA, and MLR as the types of chemometric approach. QSAR/QSPR models were proposed based on chosen st...
Source: Medicinal Chemistry Research - August 10, 2018 Category: Chemistry Source Type: research

Synthesis, anti-parasitic activity and QSAR study of a new library of polysubstituted tetrahydronaphtho[1,2- b ]azepines
AbstractA new series of twenty two 2-exo-aryl(heteroaryl)-1,4-epoxytetrahydronaphtho[1,2-b]azepines8–10 and eighteencis-2-aryl(heteroaryl)-4-hydroxytetrahydronaphtho[1,2-b]azepines11–13 were synthesized, and most of them were tested for their ability to inhibit the in vitro growth of the extracellular forms ofTrypanosoma cruzi andLeishmania infantum parasites. Cell toxicity was also determined on Vero and THP-1 mammalian cells. Seventeen compounds exhibited potent activity against the epimastigotes (IC50 lower than 20  µM), without cytotoxicity on Vero cells. Ten compounds also showed remarkable an...
Source: Medicinal Chemistry Research - August 9, 2018 Category: Chemistry Source Type: research

Effect of pterostilbene complexed with cyclodextrin on rat liver: potential reduction of oxidative damage and modulation redox-sensitive proteins
The objectives of this study were to promote the aqueous solubility of pterostilbene (PTS) by complexation with hydroxypropyl- β-cyclodextrin (HPβCD), characterize the complex under physical aspects, to make its oral administration feasible in biological tests, and to investigate their pharmacological properties. For 14 days, rats received daily PTS:HPΒCD complex at doses of 25, 50, or 100 mg kg−1 per day orally. The results showed no kidney or liver damage, nor any induction of apoptosis by the administered doses. Also, the complex showed dose-dependent antioxidant effects in the rat liv...
Source: Medicinal Chemistry Research - August 8, 2018 Category: Chemistry Source Type: research

Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid
AbstractA novel podophyllotoxin-lonidamine hybrid was synthesized, and evaluated for its in vitro cytotoxicity by CCK-8 assay. The conjugate,Da, exhibited comparable antiproliferative activity in human normal and multidrug-resistance leukemia cancer cells. Flow cytometry suggested thatDa could induce G2 phase cycle arrest and apoptosis of resistant K562/VCR cells, simultaneously increase the mitochondrial membrane depolarization. Furthermore, immunocytochemistry showed thatDa could significantly disrupt the microtubule organization in K562/VCR cells. Molecular modeling demonstrated thatDa was able to bind into the colchici...
Source: Medicinal Chemistry Research - August 8, 2018 Category: Chemistry Source Type: research

In vitro leishmanicidal activity of lactone 1,4-dihydroquinoline derivatives against Leishmania (Leishmania) amazonensis
AbstractA series of lactone 1,4-dihydroquinoline derivatives4 (4 and4aa–4cm) was screened for in vitro antileishmanial activity against the promastigote form ofLeishmania (Leishmania) amazonensis. Screening results indicate that all of the synthesized compounds significantly reduced the growth of promastigote forms of promastigotes ofL. (L.) amazonensis. The cytotoxicity of the most active compounds was also measured on peritoneal macrophage cells. Compounds4ah and4bn showed better activities than other derivatives with IC50 values of 6.22 and 9.05  μM, respectively, with selectivity index 22 and 15 times l...
Source: Medicinal Chemistry Research - August 7, 2018 Category: Chemistry Source Type: research

Computational molecular modelling of N -cinnamoyl and hydroxycinnamoyl amides as potential α-glucosidase inhibitors
AbstractIn the present work, a molecular modelling has been performed on a total of 17 cinnamic acids, derived with different amino acids. These have recently been evaluated as potential α-glucosidase inhibitors. Consequently, we proposed a quantitative 3D structure–activity relationships in order to obtain predictive models of the biological activity. Two types of descriptors were used for the modelling: quantum chemical and multi-linear algebraic maps. The first one was obtaine d by using Density Functional Theory (DFT) at the M06/6-311++G(d,p) level, while for the second, attribute sets were obtained by usin...
Source: Medicinal Chemistry Research - August 6, 2018 Category: Chemistry Source Type: research

Development of hydroxamic acid derivatives as anticancer agent with the application of 3D-QSAR, docking and molecular dynamics simulations studies
AbstractThe inhibition of histone deacetylase (HDAC) has become a well-recognized target for cancer therapy. Until now only five HDAC inhibitors i.e., SAHA, romidepsin (FK-228), belinostat, chidamide, and panobinostat have been approved by FDA. The first four of them are being employed for the treatment of cutaneous T-cell lymphoma and last one is being used for the treatment of multiple myeloma. In the present study, structure and ligand-based computational approaches were selected to design novel histone deacetylase inhibitors. A ligand-based pharmacophore model was developed employing phase module that exhibited five si...
Source: Medicinal Chemistry Research - August 4, 2018 Category: Chemistry Source Type: research

Synthesis, anticonvulsant activity, and molecular modeling studies of novel 1-phenyl/1-(4-chlorophenyl)-2-(1 H -triazol-1-yl)ethanol ester derivatives
AbstractA series of new ester derivatives were synthesized by the reaction of various acids with 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol and in vivo screened for their anticonvulsant activity. The title compounds were screened against MES and ScM seizure tests according to a modified version of the Epilepsy Therapy Screening Program (ETSP) protocol of the National Institutes of Health (NIH). Their neurotoxic effects were evaluated by the rotarod test. All the compounds showed protection against MES and/or ScM-induced seizures at 30  mg/kg without neurotoxicity. More compounds were found active in the ...
Source: Medicinal Chemistry Research - August 2, 2018 Category: Chemistry Source Type: research

Convenient one-pot synthesis of resin acid Mannich bases as novel anticancer and antifungal agents
AbstractThe one-pot three-component CuCl-catalyzed aminomethylation of the abietane diterpenoid propargyl esters by formaldehyde and secondary amines was studied for the first time. The novel diethylamino, pyrrolidine, and morpholine-substituted butynyl derivatives of abietic, dehydroabietic, levopimaric, maleopimaric and dihydroquinopimaric acids were obtained. It was shown that synthesis of the abietic acid propargyl ester by the reaction of the abietane diterpenoid with oxalyl chloride and dimethylformamide is accompanied by the formylation of the ringB at the C-7 position and the dehydrogenation of the ringC to form th...
Source: Medicinal Chemistry Research - August 2, 2018 Category: Chemistry Source Type: research

Isoindolines/isoindoline-1,3-diones as AChE inhibitors against Alzheimer ’s disease, evaluated by an improved ultra-micro assay
AbstractAlzheimer ’s disease (AD), the most common form of dementia, is characterized by a progressive degeneration of the brain that leads to loss of memory and deterioration of others cognitive functions. The only drugs currently approved for treating AD are AChE inhibitors (AChEIs). We previously tested a novel isoindoline-1,3-dione, finding potent inhibition of AChE, in part because the two carbonyl groups of phthalimide facilitate hydrogen bonds with the enzyme. The aims of the present study were: (A) To achieve a faster and cheaper technique with a reduced quantity of reactive, without significant diffe rence i...
Source: Medicinal Chemistry Research - July 30, 2018 Category: Chemistry Source Type: research

Revisiting the molecular mechanism of acquired resistance to reversible tyrosine kinase inhibitors caused by EGFR gatekeeper T790M mutation in non-small-cell lung cancer
ConclusionEAI045, the first fourth-generation EGFR inhibitor, exhibits a moderate affinity to EGFR andpossesses an exquisite selectivity for wild type over mutant kinase (~3-fold). This is expected if consideringthat the EAI045 is an allosteric inhibitor, which does not need to directly compete with ATP, and high affinityand selectivity are therefore not required for the inhibitor. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - July 28, 2018 Category: Chemistry Source Type: research

Evaluation of the effect of 2-(2,4-dihydroxyphenyl)-4 H -benzofuro[3,2- d ][1,3]thiazin-4-one on colon cells and its anticancer potential
AbstractIn this paper, we present the biological effect of the newly synthesized 2-(2,4-dihydroxyphenyl)-4H-benzofuro[3,2-d][1,3]thiazin-4-one (DPBT) on human colon adenocarcinoma cell lines (HT-29 and LS180). Additionally, DPBT cytotoxicity was examined in human colon epithelial cells (CCD 841 CoTr) and human skin fibroblasts (HSF). The studies revealed a significant decrease in the proliferation of cancer cells after exposure to DPBT at concentrations in the range of 10 –100 µM. Additionally, DPBT was not toxic to normal CCD 841 CoTr and HSF cells at concentrations that induced inhibition of cancer cel...
Source: Medicinal Chemistry Research - July 25, 2018 Category: Chemistry Source Type: research

Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti- Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study
AbstractSynthesis and investigation of antifungal, anticonvulsant and anti-Toxoplasma gondii activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole3a–3j are presented. Among the derivatives, compounds3a–3d and3f–3j possess very high activity againstCandida spp. ATCC with MIC  = 0.015–7.81 µg/ml. Compounds3a–3d and3f–3j possess also very high activity towards most of strains ofCandida spp. isolated from clinical materials with MIC  = 0.015–7.81 µg/ml. The activity of these compounds is similar and even higher than...
Source: Medicinal Chemistry Research - July 21, 2018 Category: Chemistry Source Type: research

Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones
AbstractN,N ’-Bis[1-aryl-3-pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides(R1 –R7) were synthesized by the reaction of 2 mols of 1-aryl-3-(pyrrolidine-1-yl)-1-propanone hydrochlorides with 1  mol of hydrazine hydrate and reported for the first time with their detailed spectral analysis and cytotoxicities towards human hepatoma (Huh7) and breast cancer (T47D) cell lines. Compounds R2, R6, and R7 with the IC50 values of 5.16, 6.96, and 5.96 μM, respectively, showed higher cytotoxic potency than the reference compound 5-FU with 7.0 μM against Huh7 cell line. However, all compounds did not show...
Source: Medicinal Chemistry Research - July 21, 2018 Category: Chemistry Source Type: research

Development of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as a novel chemical series of BRD4 inhibitors
In this study, we designed and synthesized 11 novel 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives and evaluated their BRD4 inhibitory activities. Most of these compounds exhibited moderate BRD4 inhibitory activities in vitro. It is worth noting that compound14a showed excellent BRD4(1) and BRD4(2) inhibitory activity with IC50 values of 350 and 290  nm, respectively. Meanwhile, remarkable anti-proliferative activities toward BRD4-sensitive cancer lines MV4-11 and HL-60 were also observed. In addition, molecular docking studies was utilized to elaborate the key interactions between compound14a and BRD4 in detai...
Source: Medicinal Chemistry Research - July 19, 2018 Category: Chemistry Source Type: research

Synthesis and biological evaluation of coumarin clubbed thiazines scaffolds as antimicrobial and antioxidant
AbstractA new series of 4-methyl-6-nitro-2-oxo-2H-chroman-7yl-2-(4-(4-fluorophenyl)-6-phenyl-2H-1,3-thiazin-2-yl-amino)acetates5a–j were synthesized from 6-nitro-4-methyl coumarinyl chloroacetate (5) and 2-amino thiazines (IIIa–j). The structure of the final compounds was adequately confirmed via spectroscopic techniques (IR,1H NMR,13C NMR, Mass) and characterization of physical properties. Final compounds were screened for their antimicrobial, antitubercular, and antioxidant activities. Compounds5c and5h found to have antibacterial potency againstE. coli with MIC values 50  µg/mL compared to stand...
Source: Medicinal Chemistry Research - July 17, 2018 Category: Chemistry Source Type: research

Novel triazoles of 3-acetylbetulin and betulone as anticancer agents
AbstractThe CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were evaluated for their anticancer activity in vitro against amelanotic melanoma C-32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3 ’-Deoxythymidine-5’-yl)-1H-1,2,3-triazol-4-yl]carbonylbetulone6e exhibited a significant IC50 value (0.17  µM) against the human glioblastoma SNB-19 cell line, an almost 5-fold higher potency while compared with reference cisplatin. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - July 17, 2018 Category: Chemistry Source Type: research

Naturally bioactive compounds from Hemimycale aff arabica : antimicrobial, antiglycation, cytotoxicity, and molecular docking studies
AbstractTwo naturally new cyclic urea and amide derivatives, [1,3]-diazepan-2-one (1) and (S)-1,4-diaza-cyclododecane-2,3-dion (2), were isolated from the organic extract of the spongeHemimycale aff arabica collected from the Red Sea. This was together with 4-acetamido-2,6-dibromo-4-hydroxy-1,1-dimethoxycyclohexa-2,5-diene (3), 2,4-bis(1-methyl-1-phenylethyl)-phenol (4),β-sitosterol (5), bis-[2-ethyl]-hexyl-phthylester, triglyceride fatty acid ester, and linoleic acid. The chemical structures of compounds1 and2 were determined based on 1D and 2D Nuclear Magnetic Resonance (NMR) and HR-ESIMS. Compounds1 and2 revealed h...
Source: Medicinal Chemistry Research - July 17, 2018 Category: Chemistry Source Type: research

Docking study and antiosteoporosis effects of a dibenzylbutane lignan isolated from Litsea cubeba targeting Cathepsin K and MEK1
AbstractLitsea cubeba (Lour.) Pers. (Lauraceae family) has been used as a folk prescription in China for the treatment of rheumatic diseases for a long time. Previous studies of our laboratory have indicated that 9 ′-O-di-(E)-feruloyl-meso-5, 5 ′-dimethoxy-secoisolariciresinol (FCL) which is a dibenzylbutane lignan enriched inL. cubeba displayed anti-inflammatory activity in LPS induced RAW264.7 cells. The present study was aimed to investigate anti-osteoporosis/anti-rheumatoid arthritis (RA) properties of FCL and explore its potential molecular targets. The anti-RA and anti-osteoporosis properties were evaluat...
Source: Medicinal Chemistry Research - July 14, 2018 Category: Chemistry Source Type: research

Synthesis of NSAIDs –Se derivatives as potent anticancer agents
AbstractIn the present study, a series of NSAIDs –Se derivatives include selenocyanates and diselenides were synthesized and characterized, their anticancer activities against the human cancer cell lines SW480, HeLa, A549, and HepG2 were determined. Interestingly, most of the new compounds showed active in reducing the viability of different can cer lines. Compounds1a and1m exhibited higher promising activities than other derivatives. As the most active compound1a showed IC50 values lower than 20  μM against the four cancer cell lines, particularly against SW480 with IC50 values below 10  μm, it s...
Source: Medicinal Chemistry Research - July 12, 2018 Category: Chemistry Source Type: research

Cytotoxicity against cholangiocarcinoma and HepG2 cell lines of lignan derivatives from Hernandia nymphaeifolia
AbstractTwelve lignan derivatives were synthesized from deoxypodophyllotoxin isolated fromHernandia nymphaeifolia. Cytotoxicity evaluation against cholangiocarcinoma, KKU-100, and HepG2 cell lines showed that compounds3,9,10, and13 exhibited stronger cytotoxicity than the starting material,1, with IC50 ranging from 0.42 to 2.01  μM. Compound10 displayed interesting activity by showing IC50 values of 0.75 and 0.46  μM against KKU-100 and HepG2 cell lines, respectively. From these observation,10 seems to be useful as a lead compound for the development of anticancer agents. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - July 10, 2018 Category: Chemistry Source Type: research

Extraction method and anti-cancer evaluation of two lignans from Phyllanthus Niruri L .
In this study the potential use of an aqueous two phase system (ATPS) for the extraction of two lignans fromPhyllanthus Niruri L. was evaluated and optimized using response surface methodology (RSM). Their anti-cancer potential against human lung cancer cell line A549, hepatic cancer cell line SMMC-7721, gastric cancer cell line MGC-803 were also evaluated respectively. The result showed that lignan hypophyllanthin displayed obvious anti-cancer activity in all of three cell line, but lignan phyllanthin only performed significant activity against SMMC-7721 cell line. Besides, the MOE program docking research of two compound...
Source: Medicinal Chemistry Research - July 7, 2018 Category: Chemistry Source Type: research

Synthesis, antitumor and antimicrobial evaluation of novel 1,3,4-thiadiazole derivatives bearing disulfide bond
AbstractIn the present study, the synthesis of novel 1,3,4-thiadiazole derivatives bearing disulfide bond are accomplished in good yields with employing a convergent synthetic route, and their in vitro antiproliferative activities were screened against human cancer cell lines A549, Hela, SMMC-7721, and normal cell lines L929 by CCK-8 assay. Meanwhile, all compounds were evaluated for their in vitro antimicrobial activities against Gram-negative bacteriaEscherichia coli and Gram-positive bacteriaStaphylococcus aureus strains. Screening results indicated that some of the tested compounds6a–6h,7a–7h, and8a–8...
Source: Medicinal Chemistry Research - July 5, 2018 Category: Chemistry Source Type: research

Synthesis and DNA binding of new adenine derivatives incorporating 5-((Alkylthio)-1,3,4-oxadiazol-2-yl)methyl moiety
In this study, a series of new adenine derivatives possessing 1,3,4-oxadiazole moiety with differentS-alkyl group were synthesized. The structures of these compounds were established on the basis of FT-IR,1H,13C-APT NMR, and HRLC-MS spectral data. Their DNA binding abilities were investigated in vitro by agarose gel electrophoresis. The relationship between the structure and the mentioned biological activities was discussed. The results showed that these compounds5d and5c exhibited DNA cleavage activity. Compounds DNA interaction studies reveal that compounds have affinity towards A/A and G/G nucleotides on DNA. None of th...
Source: Medicinal Chemistry Research - July 2, 2018 Category: Chemistry Source Type: research

Antioxidant and anti-inflammatory oxygenated meroterpenoids from the thalli of red seaweed Kappaphycus alvarezii
AbstractThree antioxidant and anti-inflammatory oxygenated meroterpenoids, 1-(3-methoxypropyl)-2-propylcyclohexane (C13) (1), 3-(methoxymethyl)heptyl 3-(cyclohex-3-enyl) propanoate (C18) (2), and 2-ethyl-6-(4-methoxy-2-((2-oxotetrahydro-2H-pyran-4-yl)methyl)butoxy)-6-oxohexyl 5-ethyloct-4-enoate (C29) (3) were purified from the methanol:ethyl acetate fraction of red seaweedKappaphycus alvarezii (family Solieriaceae) collected from the Gulf-of-Mannar on the southeast coast of peninsular India. The highly oxygenated C29 meroterpenoid3 displayed potential antioxidative activities (IC50 
Source: Medicinal Chemistry Research - July 2, 2018 Category: Chemistry Source Type: research

Correction to: Inhibitor discovery from pomegranate rind for targeting human salivary α-amylase
The original version of this article unfortunately contained error in the captions of Figs. 10 –12. The correct figure captions are presented with this erratum. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 28, 2018 Category: Chemistry Source Type: research

Synthesis and in vitro activities on anti-platelet aggregation of 4-methoxyisophthalamides
AbstractA series of 4-methoxyisophthalamides (1d –1w) were designed and synthesized and their chemical structures were confirmed by IR, MS,1H-NMR, and13C-NMR. The in vitro on anti-platelet aggregation activities of these compounds were assessed by using Born method. Compounds with higher activities were selected to continue research via Cell Counting Kit-8 (CCK-8) assays of their cytotoxicities. Biological screening results revealed four compounds 1h, 1i, 1q, and 1v exhibited higher activities than the control drugs on against the platelet aggregation induced by adenosine triphosphate (ADP). Moreover, compounds 1p an...
Source: Medicinal Chemistry Research - June 26, 2018 Category: Chemistry Source Type: research

Simulation results source for the identification of biological active compounds: synthesis, antimicrobial evaluation and SARs of three in one heterocyclic motifs
In this study we present the synthesis, characterization, and evaluation of biological potency of4(a–g),5(a–g), and7(a–g) by conducting structure –activity relationship (SAR) studies. Further conducting density functional theory (DFT) simulation studies for entitled compounds4(a–g),5(a–g), and7(a–g) allowed us to fully study the effect of the changes of electronic and molecular structures on their biological activity by demonstrating the role of frontier molecular orbitals, in particular LUMO. The electron withdrawing nitro group substituted compounds5d and7d have higher activity t...
Source: Medicinal Chemistry Research - June 25, 2018 Category: Chemistry Source Type: research

Uses of dimedone for the synthesis of new heterocyclic derivatives with anti-tumor, c-Met, tyrosine, and Pim-1 kinases inhibitions
AbstractThe reaction of dimedone (1) with any of the diazonium salts2a –c to give the arylhydrazone derivatives3a –c. The Gewald ’s reaction of any of compounds3a –c using elemental sulfur and either of malononitrile or ethyl cyanoacetate gave the thiophene derivatives5a –f, respectively. Compounds5a,5c, and5e underwent a series of heterocclization reactions to give potentially anticancer agents. The newly synthesized compounds were evaluated for their in vitro cytotoxic activity against c-Met kinase, and the six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721). All ...
Source: Medicinal Chemistry Research - June 25, 2018 Category: Chemistry Source Type: research

New histone deacetylase inhibitors from the twigs of Melanorrhoea usitata
AbstractTwo new compounds, melanorrone (1) and melanorric acid (2), as well as 19 known compounds were isolated and identified from the twigs ofMelanorrhoea usitata. Their structures were determined by spectroscopic methods (IR,1H-NMR,13C-NMR, 2D-NMR, MS, and ECD). The histone deacetylase (HDAC) inhibitory activities of the obtained compounds were evaluated. Melanorrone (1) along with five known compounds acted as good HDAC inhibitors at 100  μM. Molecular docking experiments of these compounds with representatives of class I (HDAC2 and HDAC8) and class II (HDAC4 and HDAC7) HDAC isoforms displayed potential isofo...
Source: Medicinal Chemistry Research - June 23, 2018 Category: Chemistry Source Type: research

Design, synthesis, and biological evaluation of thiomatrine derivatives as potential anticancer agents
AbstractA series of new thiomatrine derivatives was designed and synthesized for their potential application as anticancer agents. The structure of these compounds was characterized by1H-NMR,13C-NMR, and ESI-MS spectral analyses. Single crystals of compound 3k were obtained by recrystallization and the structure was further confirmed by X-ray diffraction determination. All the target compounds were evaluated for their in vitro cytotoxicity against human cancer cell lines A549 and HepG2. Among these compounds, the derivative 3aa displayed the most significant anticancer activity against four cancer cell lines with IC50 valu...
Source: Medicinal Chemistry Research - June 23, 2018 Category: Chemistry Source Type: research

Platanic acid-derived methyl 20-amino-30-norlupan-28-oates are potent cytotoxic agents acting by apoptosis
AbstractA set of eight derivatives of betulinic acid (2) and 12 derivatives of platanic acid (3) has been prepared and screened for their cytotoxic activity using SRB assays. First synthetic approaches were focused on the preparation of augustic acid (4) analogs of2 and3 by introducing a second hydroxyl group on the A-ring of both triterpenoic acids leading to compounds5–14. Further structural modifications were performed at the C-20 keto group of the platanic acid backbone by its transformation into an oxime moiety and subsequent reduction to 20-amino-30-norlupan derivatives17–24. In the SRB assays low EC50 va...
Source: Medicinal Chemistry Research - June 22, 2018 Category: Chemistry Source Type: research

Synthesis and biological investigations of 3 β-aminotropane arylamide derivatives with atypical antipsychotic profile
AbstractThis work is a continuation of our previous research, concentrating this time on lead structure modification to increase the 5-HT1A receptor affinity and water solubility of designed compounds. Therefore, the compounds synthesised within the present project included structural analogues of 3 β-acylamine derivatives of tropane with the introduction of a methyl substituent in the benzyl ring and a 2-quinoline, 3-quinoline, or 6-quinoline moiety. A series of novel 3β-aminotropane derivatives was evaluated for their affinity for 5-HT1A, 5-HT2A, and D2 receptors, which allowed for the identification of compoun...
Source: Medicinal Chemistry Research - June 22, 2018 Category: Chemistry Source Type: research

Synthesis and anti- Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives
AbstractNine 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents in the 4-position of the phenyl group and benzenesulfonamide moiety were synthesized and evaluated againstPlasmodium falciparum. Six compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 5.13 to 12.22  µM. The most active derivative with substituents R1 = F / R2 = CH3 exhibited an IC50 value of 5.13  µM and an IS value of 62.90, which was higher than that of the control drug sulfadoxine. For this reason, it is ...
Source: Medicinal Chemistry Research - June 20, 2018 Category: Chemistry Source Type: research

Synthesis and antiproliferative activity of 3- and 7-styrylcoumarins
AbstractA series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl-7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids6e,10c, and10d, exhibited the highest activity (IC50- SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,...
Source: Medicinal Chemistry Research - June 19, 2018 Category: Chemistry Source Type: research

New bioactive chlorinated cyclopentene derivatives from the marine-derived Fungus Phoma sp
We report here the new compounds1–3 and the crystallographic data of compound4 for the first time. Additionally, we report significant antimicrobial activity of compounds1–3 againstEscherichia coli,Bacillus subtilis,Mycobacterium phlei, andStaphylococcus aureus and they showed no lethality against brine shrimp. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 16, 2018 Category: Chemistry Source Type: research

Design, synthesis, and biological evaluation of Cyclobentinib (CB1107) as a potential anti-CML agent
AbstractCyclobentinib was designed and synthesized as a novel anti-CML agent, its in vitro activity against K562 cells was evaluated by MTT assay. CB1107 showed remarkable cytotoxicity against K562 cell line with an IC50 of 0.037  ± 0.028 μmol/L, and thus it was 17-fold more potent than the reference drug Imatinib. Inducing cell apoptosis and affecting cell cycling of this compound in K562 cells were estimated by using flow cytometry and Acridine Orange/Ethidium Bromide (AO/EB) staining. The results showed that CB110 7 was capable of arresting cell cycle at G0/G1 phase as well as inducing cel...
Source: Medicinal Chemistry Research - June 15, 2018 Category: Chemistry Source Type: research

Design, synthesis and pharmacological evaluation of carboxamide and carbothioamide derivatives of 1,3,4-thiadiazole as the inhibitors of acetylcholinesterase and oxipiperazine)ative stress for the management of cognitive debility
AbstractAcetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this and our previous findings on the ameliorative effects of amide derivatives of 1,3,4-thiaidiazoles on cognitive deterioration, the present study demonstrated the design, synthesis and pharmacological evaluation of carboxamides and carbothioamide derivatives of 1,3,4-thiadiazole. Novel carboxamide and carbothioamide derivatives were synthesised and characte...
Source: Medicinal Chemistry Research - June 12, 2018 Category: Chemistry Source Type: research

Bavachinin analogues as agonists of pan-peroxisome proliferator-activated receptors
In this study, five isoflavones, three isoflavanones, and five scaffold-hopping analogues of bavachinin were designed, synthesised, and evaluated through reporter gene assays for pan-PPAR agonist activity. The analogue 2-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-2,3-dihydroquinolin-4(1H)-one (21) was identified as a pan-PPAR agonist, exhibiting substantially higher PPAR α/β agonist activity and equal PPAR-γ agonist activity than does bavachinin. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 11, 2018 Category: Chemistry Source Type: research

Synthesis, docking study, and biological evaluation of novel umbellipherone/hymecromone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors
AbstractA novel hybrid series of umbellipherone and benzyl amine scaffolds, linked via triazole ring, was synthesized and evaluated as both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Most of the synthesized compounds showed moderate to high activities by using Ellman ’s modified assay. Among the target compounds,6e bearing 3-methoxy substituent on benzyl moiety was the most active one (AChE and BuChE IC50 = 3.4 and 1.1 μM, respectively). Finally, binding modes of the target compound was studied using molecular docking stimulations. The neuroprotectivity evaluatio...
Source: Medicinal Chemistry Research - May 30, 2018 Category: Chemistry Source Type: research

3,4-Dihydro-quinolin-2-one derivatives from extremophilic Streptomyces sp. LGE21
AbstractThree new naturally-occurring 3,4-dihydroquinoline-2-one derivatives: 8-Hydroxy-3,4-dihydro-1H-quinolin-2-one (1), 3,4-dihydro-1H-quinolin-2-one (2) and 8-methoxy-3,4-dihydro-1H-quinolin-2-one (3), together with linoleic acid, glycerol monolinoleate and phenyl acetic acid were isolated from theStreptomyces sp. LGE21, derived fromLemna gibba. Structures of the new alkaloids (1–3) were determined by extensive 1D and 2D NMR, and MS measurements. In vitro cytotoxic studies of1–3 and linoleic acid, in comparison with the original extract were assayed against liver cancer HEPG2 cell line and the human cervix ...
Source: Medicinal Chemistry Research - May 24, 2018 Category: Chemistry Source Type: research

Exploring inhibition mechanism and nature of lipase by Ligupurpuroside A extracted from Ku-Ding tea
This study should be helpful for the design of diet drug and the full use of Ligupurpuroside A in food industry. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - May 24, 2018 Category: Chemistry Source Type: research

Secondary metabolites from two Hispaniola Ageratina species and their cytotoxic activity
AbstractStudy of the aerial parts of the two species ofAgeratina:A. dictyoneura andA. illita afforded four newent-labdane diterpenoids (1–4). Two known labdanes: 2 β,3α,15-trihydroxy-ent-labd-7-ene (5), and 2 β,3α-trihydroxy-ent-labd-7-en-15-oic acid (6); two sesquiterpene lactones: 8 β-hydroxy-β-cyclocostunolide (7) and eupatoriopicrin (8), one benzofuran, and six flavonoids were also isolated. Their chemical structures were determined based on extensive spectroscopic study, comparison with reported data and chemical transformations. The cytotoxicity of the newent-labdane diterpenoids...
Source: Medicinal Chemistry Research - May 24, 2018 Category: Chemistry Source Type: research

Antioxidant and anticholinesterase activities of Ferulago syriaca Boiss. and F. isaurica Pe șmen growing in Turkey
AbstractFerulago species have been utilized since ancient times as anthelmintic, digestive, sedative, and aphrodisiac, along with salads or as seasoning in view of their special odors. The study reports the antioxidant and anticholinesterase activities of extracts, fractions from roots, and aerial parts together with isolated compounds from chloroform fractions of roots [isoimperatorin (1), bergapten (2), prantschimgin (3), xanthotoxin (4), and felamidin (5)] fromFerulago syriaca Boiss. andF. isaurica Pe șmen. The phenolic contents and antioxidant activities of extracts, fractions, and isolated compounds were performed wi...
Source: Medicinal Chemistry Research - May 24, 2018 Category: Chemistry Source Type: research

Synthesis and evaluation of antinociceptive and anti-inflammatory effects of nitro-porphyrins
AbstractThis manuscript reports the anti-inflammatory and antinociceptive effects of 4 nitrophenyl-porphyrins: 5,10,15,20-tetra-(3-nitrophenyl)-porphyrin (TNPP), 5,10,15,20-tetra-(4-fluoro-3-nitrophenyl)-porphyrin (TpFNPP), 5,10,15,20-tetra-(4-chloro-3-nitrophenyl)-porphyrin (TpClNPP), and 5,10,15,20-tetra-(4-bromo-3-nitrophenyl)-porphyrin (TpBrNPP). The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) induced ear edema. The in vitro anti-inflammatory assay was carried out using J774A.1 murine macrophages stimulated with LPS. All nitro-porphyrins decreased inf...
Source: Medicinal Chemistry Research - May 24, 2018 Category: Chemistry Source Type: research

Combined topomer CoMFA and hologram QSAR studies of a series of pyrrole derivatives as potential HIV fusion inhibitors
AbstractTo have a better understanding of the relationship between structures and inhibitory activities of HIV fusion inhibitors, topomer comparative molecular field analysis (Topomer CoMFA) and hologram quantitative structure –activity relationship (HQSAR) were applied to study a series of pyrrole derivatives as potential HIV fusion inhibitors. Statistical results from the Topomer CoMFA model showed believable predictability based on the non-cross-validated value (r2 = 0.96), and the cross-validated value (q2 = 0.63). Ther2 andq2 from the HQSAR model were 0.96 and 0.66, respectively, whic...
Source: Medicinal Chemistry Research - May 21, 2018 Category: Chemistry Source Type: research

Design, synthesis and cytotoxic evaluation of quinazoline-2,4,6-triamine and 2,6-diaminoquinazolin-4(3 H )-one derivatives
AbstractA series of quinazoline-2,4,6-triamine (quinazoline) and 2,6-diaminoquinazolin-4(3H)-one (quinazolinone) derivatives were designed, synthesized and evaluated as cytotoxic agents in three cancer cell lines (HCT-15, SKOV-3, and MDA-MB-231) using conventional MTT assay. Of the tested compounds, only eleven quinazoline derivatives showed activity against all the tested cell lines, at 24  h of exposure. Among them, the compounds3e and3f exhibited the highest cytotoxic activity, with the most important IC50 values ranging from 4.5 to 15.5  μM. They were more active than the reference drugs (Gefitinib, PD...
Source: Medicinal Chemistry Research - May 21, 2018 Category: Chemistry Source Type: research

Inhibitor discovery from pomegranate rind for targeting human salivary α-amylase
This study explored the effects of the main active compounds of the pomegranate (Punica granatum L.) rind extract on the activity of the human salivary α-amylase and their molecular inhibitory mechanisms. Four compounds exhibited remarkable inhibitory activities against α-amylase, including (1) rutin, (2) luteolin, (3) quercetin, and (4) kaempferol. The IC50 values were found to be 265.65, 59.67, 99.56, and 139.72  μM for rutin, luteolin, quercetin, and kaempferol, respectively. The kinetic study using the Lineweaver–Burk revealed the four compounds showed a non-competitive inhibition against &a...
Source: Medicinal Chemistry Research - May 18, 2018 Category: Chemistry Source Type: research

Selective and novel cyclin-dependent kinases 4 inhibitor: synthesis and biological evaluation
AbstractA series of novel LEE011 derivatives containing pyridine N-oxide were designed, synthesized and evaluated. Systematic study of the structure-activity relationship (SAR) improves the selectivity for CDK4 and led to the identification of compound9a. The compound showed comparable CDK4 kinase activity with ribociclib and greater selectivity over the closely related CDK6 kinase. The selective CDK4 inhibitor9a has been demonstrated the antitumor activity via G1 phase cell cycle arrest, as well as dual CDK4/CDK6 inhibitor ribociclib and significantly down-regulated the activity of CDK4-cyclinD-Rb pathway of tumor cells. ...
Source: Medicinal Chemistry Research - May 18, 2018 Category: Chemistry Source Type: research