Synthetic 3-alkylpyridine alkaloid analogues as a new scaffold against leukemic cell lines: cytotoxic evaluation and mode of action
AbstractLeukemia is a malignant disease that originates in the bone marrow, local of blood cells production. Chemotherapy treatment is one of the alternatives to improve the survival of patients. In this context, the search for new compounds with potential cytotoxic action is justified. The present work evaluated the cytotoxic activity of 16 new synthetic analogs of 3-alkylpyridine alkaloids. The cytotoxic profiles were determined by MTT in vitro assay against THP-1 (acute monocytic leukemia), K562 (chronic myeloid leukemia) and PBMC (peripheral blood mononuclear) human cells. To investigate the mechanism of action, cell c...
Source: Medicinal Chemistry Research - July 19, 2019 Category: Chemistry Source Type: research

Screening of 1,2-furanonaphthoquinones 1,2,3-1 H -triazoles for glycosidases inhibitory activity and free radical scavenging potential: an insight in anticancer activity
AbstractIn many cancer cells, glycoproteins show abnormal glycosylation patterns which have been associated with tumor initiation, progression, and metastasis. Thus, the glycosidases involved in glycoprotein maturation represent good targets for the development of new anticancer agents. In a previous report, we synthetized and evaluated the cytotoxic effect of a novel series of nor- β-lapachone tethered to 1H-1,2,3-triazoles (1,2-FNQT,9a–r) against a panel of leukemia cell lines. Many 1,2-FNQT were active at low micromolar concentration and some were selective for cancer cells rather than normal ones. These resu...
Source: Medicinal Chemistry Research - July 18, 2019 Category: Chemistry Source Type: research

Synthesis, antimicrobial evaluation, and molecular docking of some new angular allylbenzochromone derivatives
AbstractDifferent classes of antimicrobial compounds such asβ-lactams, sulfonamides, aminoglycosides, tetracyclines, quinolines and others have been developed during the 20th century to control the growing antimicrobial resistance. Therefore, there is an urgent need to build up new and effective antimicrobial agents with different working mechanisms to suppress this resistance. Accordingly, the judicious design of antimicrobial organic compounds with antiquorum-sensing activities could be a major solution for this global challenge. Herein, the versatile precursor 6-allyl-3-formyl-4H-benzo[h]chromen-4-one (2) was used ...
Source: Medicinal Chemistry Research - July 17, 2019 Category: Chemistry Source Type: research

Chemical constituents from Ginkgo biloba L. male flowers and their biological activities
AbstractFrom the male flowers ofGinkgo biloba L., 26 compounds were isolated and identified including 7-O-(β-d-glucopyranosyloxy)-5-hydroxy-1(3H)- isobenzofuranone (1), piperoside (2), 3-(4-hydroxy-3-methoxyphenyl)propane-1, 2-diol (3), ginkgolide B (4), ginkgolide C (5), hexyl-β-getiobioside (6), benzyl-β-d-xylopyranosyl-(1  → 6)-β-d-glucopyranoside (7), ginkgolic acid (8), kaempferol-3-O-[6 ′′′-O-p-coumaroyl-β-d-glucopyranosyl-(1  → 2)-α-l-rhamnopyrano-side] (9), quercetin-3-O-[6 ′′′-O-p-coumaroyl-β-d-glucopyrano...
Source: Medicinal Chemistry Research - July 14, 2019 Category: Chemistry Source Type: research

Design and synthesis of novel 4-hydrazone functionalized/1,2,4-triazole fused pyrido[2,3- d ]pyrimidine derivatives, their evaluation for antifungal activity and docking studies
AbstractA series of novel 2-substituted 4-hydrazone functionalized pyrido[2,3-d]pyrimidine (8a–f and9a–e) and 1,2,4-triazole fused pyrido[2,3-d]pyrimidine derivatives (10a–f and11a–e) were prepared starting from ethyl 2-amino-6-(trifluoromethyl)nicotinate3 via acylation, cyclization, chlorination, hydrazine reaction, hydrazone formation followed by intramolecular cyclization. All the final products were screened against variousCandida strains for determining the antifungal activity, minimum fungicidal concentration and inhibition of ergosterol biosynthesis. Among the screened, compounds8c,8f,9c,10f,...
Source: Medicinal Chemistry Research - July 13, 2019 Category: Chemistry Source Type: research

Potent anti-MRSA activity and synergism with aminoglycosides by flavonoid derivatives from the root barks of Morus alba , a traditional Chinese medicine
AbstractInfections of clinical methicillin-resistantStaphylococcus aureus (MRSA) is a very tough public health problem and a challenge of new drug development. Nearly 90 Diels-Alder adducts (DAAs) have so far been isolated fromMorus plants, but only a few of them have been evaluated for their anti-MRSA activities. To study the antibacterial compounds of DAAs from the root barks ’ section ofMorus alba L. and their synergism with antibacterial agents against clinical MRSA strains, bioassay-guided phytochemical methods were used to screen the active components. Minimal inhibitory concentrations (MICs) and minimal bacter...
Source: Medicinal Chemistry Research - July 13, 2019 Category: Chemistry Source Type: research

Correlation study of antibacterial activity and spectrum of Penicillins through a structure-activity relationship analysis
AbstractPenicillins are a group of antibiotics of the beta-lactam group, widely used worldwide as first-choice drugs in the treatment of infections caused by sensitive bacteria. Their use is based on an empirical measure of their activity through antibiograms. In this work we have carried out a structure-activity relationship analysis to elucidate the molecular and physicochemical bases that determine the antibacterial activity and the orientation of the antibacterial spectrum of penicillins, employing a set of bacteria that cause common infections. It was found that the antibacterial activity increases as penicillin size ...
Source: Medicinal Chemistry Research - July 11, 2019 Category: Chemistry Source Type: research

Structure-activity relationship for vanilloid compounds from extract of Zingiber officinale var rubrum rhizomes: effect on extracellular melanogenesis inhibitory activity
AbstractThe components in the methanol extract ofZingiber officinale var rubrum (red ginger) were isolated by a series of column chromatography and identified by Nuclear Magnetic Resonance (NMR) and Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOFMS). Thirteen components, including eleven vanilloid compounds, were isolated from the extract. All the isolated components reduced extracellular melanin contents. Structure-activity relationship studies suggested that elongation of the carbon chain of shogaol and gingerol increased the extracellular melanogenesis inhibitory activity, and tha...
Source: Medicinal Chemistry Research - July 6, 2019 Category: Chemistry Source Type: research

Synthesis and biological evaluation of novel disulfides incorporating 1,3,4-thiadiazole scaffold as promising antitumor agents
AbstractIn the present study, fourteen 2,5-disubstituted 1,3,4-thiadiazole derivatives containing disulfide group were prepared. The resulting compounds7a–7n were identified by IR, NMR, MS, and elemental analysis. Their antiproliferative properties in vitro were studied employing standard CCK-8 assay against SMMC-7721, MCF-7, and A549 lines. Bioassay indicated that some compounds showed stronger antitumor effects than reference drugs PX-12 and 5-fluorouracil. Among these screened compounds, compound7h showed excellent biological activities in inhibiting SMMC-7721 cell proliferation with IC50 at 1.93  ±&...
Source: Medicinal Chemistry Research - July 3, 2019 Category: Chemistry Source Type: research

Design, synthesis, biological evaluation and molecular modeling of new coumarin derivatives as potent anticancer agents
AbstractA novel series of coumarin-pyridine/fused pyridine hybrids were designed and synthesized. Their anticancer activity was evaluated against human cancer cell lines MCF-7, HCT-116, HepG-2, and A549. Compounds9,10, and11 showed the most potent growth inhibitory activities with IC50 values ranging from 1.1 to 2.4  μM, against MCF-7 cell line. Flow cytometric analysis revealed that these compounds induced cell cycle arrest in the G2/M phase followed by apoptotic cell death. Consistent with these results, the activity of caspase-3 in MCF-7 cells was tested. The results indicated that compounds9,10, and11 increas...
Source: Medicinal Chemistry Research - June 25, 2019 Category: Chemistry Source Type: research

Synthesis, in vitro antifungal evaluation and docking studies of novel derivatives of imidazoles and benzimidazoles
AbstractA series of imidazole and benzimidazole derivatives was designed and prepared in good yields via convenient and efficient two steps synthetic route using readily available starting materials. The structures of the synthesized compounds and their intermediates were characterized by IR,1H-NMR,13C-NMR spectroscopy, and MS spectra. The in vitro antifungal activities of the targeted compounds were evaluated againstCandida Albicans, Cryptococcus neoformans, Aspergillus niger, andMicrosporum gypseum. The results showed that some of these azole-derivatives exhibited good to excellent antifungal activities against the used ...
Source: Medicinal Chemistry Research - June 18, 2019 Category: Chemistry Source Type: research

Chemical constituents of the Vietnamese plants Dalbergia tonkinensis Prain and Cratoxylum formosum (Jack) Dyer in Hook and their DPPH radical scavenging activities
AbstractPhytochemical investigations of the leaves and roots ofDalbergia tonkinensis led to the isolation of a new isoflavone glycoside derivative, isocaviunin 7-O-β-D-apiofuranosyl-(1  → 6)-β-D-glucopyranoside (1), and a new scalemic sesquiterpene lactone, 3,7-dimethyl-3-vinylhexahydro-6,7-bifuran-3(2H)-one (2), along with the previously known compounds3-16, and nine other known compounds17-25 were isolated from the leaves ofCratoxylum formosum. The chemical structures of the isolated compounds were elucidated by 1D- and 2D-NMR analyses as well as MS spectroscopic data. The results suggest tha...
Source: Medicinal Chemistry Research - June 15, 2019 Category: Chemistry Source Type: research

Cytotoxicity of multicellular cancer spheroids, antibacterial, and antifungal of selected sulfonamide derivatives coupled with a salicylamide and/or anisamide scaffold
AbstractIn an attempt to overcome the drawbacks of the cancer monolayers model (2D), the 3-dimensional (3D) multicellular cancer spheroids (MCS) have been developed. Nine of most active sulfonamide derivatives coupled with a salicylamide scaffold were screened for cytotoxicity on two human cancer cell line spheroids (MCF7 and HCT116) in addition to one human normal cell line spheroid (RPE-1). 5-Chloro-N-[(N-4-chlorophenyl) 4-sulfamoylbenzyl] salicylamide (9) was found to be the most active compound among all tested compounds. It showed 70% inhibition on HCT116 spheroids, almost double the activity of cisplatin, and higher ...
Source: Medicinal Chemistry Research - June 14, 2019 Category: Chemistry Source Type: research

Sulfa drug analogs: new classes of N -sulfonyl aminated azines and their biological and preclinical importance in medicinal chemistry (2000 –2018)
AbstractN-sulfonylamino azinones has attracted the interest of numerous researchers and extensive investigations on their biological activities have been done. The present review provides an overview of the patents and reports filed during the last few years pertaining to the synthesisN-sulfonyl azinones as well as their biological and preclinical studies. A brief discussion on the significant biological findings is also provided. It has been established thatN-sulfonylamino azinones is privileged heterocycles possessing diuretic, antihypertensive, anti-inflammatory, and anticancer and other biological activities. In partic...
Source: Medicinal Chemistry Research - June 12, 2019 Category: Chemistry Source Type: research

Synthesis and in vitro activities on anti-platelet aggregation of 4-methoxy-1,3-phthalamidesamides and benzenedisulfonamides
AbstractCardiovascular diseases are the most frequent cause of morbidity and mortality worldwide. In order to discover novel compounds with anti-platelet aggregation activities, a series of novel 4-methoxy-1,3-phthalamidesamides (1a–1i) and a series of novel 4-methoxy-1,3-benzenedisulfon-amides (2a–2i) were synthesized and their anti-platelet aggregation activities were evaluated by the turbidimetric method in response to the following agonists: adenosine diphosphate (ADP), arachidonic acid (AA), and Collagen. Those compounds that have better in vitro activities were subjected to cell toxicity tests via cell co...
Source: Medicinal Chemistry Research - June 10, 2019 Category: Chemistry Source Type: research

Fluorophenols bearing nitrogenated heterocycle moieties, a class of novel Keap1-Nrf2 protein-protein interaction inhibitors: synthesis, antioxidant stress screening and molecular docking
This study introduced a class of fluorophenols containing nitrogenated heterocycles for the development of novel Keap1-Nrf2 protein –protein interaction (PPI) inhibitors. Keap1-Kelch is suggested the most potential target protein for such class of halophenols. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 6, 2019 Category: Chemistry Source Type: research

A structure –activity relationship study of phenyl sesquiterpenoids on efflux inhibition against Staphylococcus aureus
AbstractSixteen natural acetophenone sesquiterpene derivatives were isolated fromFerula ferulioides and 11 synthetic acetophenone sesquiterpene analogues were evaluated to explore the structure –activity relationships (SARs) on their antibacterial activities against a panel of bacteria including drug-resistantStaphylococcus aureus. The minimum inhibitory concentration (MIC) values of the compounds were in the range of 0.5 –128 mg/L. Preliminary SAR studies showed that subtle modifications on both the 2’,4’-dihydroxyphenyl moiety and the side chain reduced their activity against drug-resistant...
Source: Medicinal Chemistry Research - June 6, 2019 Category: Chemistry Source Type: research

New fluoroquinolones/nitric oxide donor hybrids: design, synthesis and antitubercular activity
AbstractNew nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds2b,3a,4a,5a, and2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulatio...
Source: Medicinal Chemistry Research - June 6, 2019 Category: Chemistry Source Type: research

3D-QSAR, molecular docking, and new compound design of pyrimidine derivatives as Src small molecule inhibitors
In this study, the structure and acitivity relationship of 51 Src small molecule inhibitors with potential pyrimidine derivatives was explored. On the basis of ligand composite, the relationsConducted a phase hip between molecular structure and inhibitory activity of MDA-MB-231/435 TNBC cell lines was studied by using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis fields (CoMSIA), and Topomer CoMFA (T-COMFA) methods, and thereby two sets of three-dimensional quantitative structure –activity relationship models were established to analyze the molecular structure and ant...
Source: Medicinal Chemistry Research - June 5, 2019 Category: Chemistry Source Type: research

Synthesis, molecular docking, and apoptogenic efficacy of novel N-heterocycle analogs to target B-cell lymphoma 2/X-linked inhibitors of apoptosis proteins to regress melanoma
AbstractThe novel series of piperidine conjugated benzophenone analogs with amide link11a–l were synthesized in a multistep process. The structures of these compounds were confirmed by IR,1H,13C, NMR, and mass spectra and also by elemental analyses. The newly synthesized molecules were screened for selectivity against cancers of different origin through cell based assay system using B16F10, A375, A549, HepG2, ACHN, and MCF7 cells. The results postulated that compound11f with two bromo groups at the para position in rings A and E and two methyl groups at ortho position in rings B and D evokes target specific action ag...
Source: Medicinal Chemistry Research - June 4, 2019 Category: Chemistry Source Type: research

Synthesis of oleanolic acid/ursolic acid/glycyrrhetinic acid-hydrogen sulfide donor hybrids and their antitumor activity
AbstractA total of 25 targeted hydrogen sulfide donor –pentacyclic triterpene hybrids were designed, synthesized and evaluated on the basis of inspiring reports about hydrogen sulfide donor molecules and oleanolic acid derivatives on anti-tumor activity. The results revealed that only some hybrids (10a,10b,12a,12b,13a, and15b) showed moderate anti-proliferation activity against K562 cell line. It indicated that oleanane-type, (R)-lipoic acid and TBZ groups were much more favorable to the anti-proliferation activity. Furthermore, C-3 OH was more beneficial than C-28/29 COOH in the oleanane-type to the antitumor activi...
Source: Medicinal Chemistry Research - June 4, 2019 Category: Chemistry Source Type: research

N , N ’-disubstitutedphenyl-4-ethoxyl benzene-1, 3-disulfonamides: design, synthesis, and evaluation of anti-platelet aggregation activity
AbstractAccording to the bio-isosterism theory, a series ofN,N’-disubstitutedphenyl-4-ethoxylbenzene-1, 3-disulfonamides (5a-p) were designed and synthesized by two steps of reactions including chlorosulfonation and ammonolysis. The structures of all compounds have been confirmed by IR,1H-NMR,13C-NMR, and ESI-MS spectra. The in vitro anti-platelet aggregation activities were evaluated by Born ’s test induced by adenosine diphosphate (ADP) and arachidonic acid (AA), respectively. The biological evaluation results revealed that compound5h had the lowest IC50 value (0.32  μM) and the highest inhibition r...
Source: Medicinal Chemistry Research - June 4, 2019 Category: Chemistry Source Type: research

QSAR-guided pharmacophore modeling and subsequent virtual screening identify novel TYK2 inhibitor
AbstractTyrosine Kinase 2 (TYK2) inhibition is of potential therapeutic value for treating autoimmune diseases. An elaborate ligand-based computational workflow was employed to explore structural requirements for TYK2 inhibition. Genetic function algorithm (GFA) was coupled to k-nearest neighbor (kNN) and multiple linear regression (MLR) analyses to search for predictive QSAR models based on optimal pharmacophore(s)/physicochemical descriptors combinations. QSAR-selected pharmacophores were validated by receiver operating characteristic (ROC) curve analysis and by comparison with crystallographic structures of known inhibi...
Source: Medicinal Chemistry Research - June 3, 2019 Category: Chemistry Source Type: research

Preparation and biological evaluation of quinoline amines as anticancer agents and its molecular docking
AbstractA series of 2-chloro N-substituted amino quinolines (2a –2j) were prepared and characterized by analytical and spectroscopic methods. As quinoline is an important pharmacophoric moiety, the prepared compounds were screened against a non-small cell lung cancer cell line, A549. One of the compounds, 2-chloro-8-methyl-N-(quinolin-5-yl)quinolin-4-amine (2b) is found to be active with inhibition concentration value of (IC50) 29.4  μM. The molecular docking studies with the predominant PI3K/AKT/mTOR pathway proteins also revealed the lesser binding energy with2b. All the compounds are predicted to satisfy...
Source: Medicinal Chemistry Research - June 1, 2019 Category: Chemistry Source Type: research

Synthesis and in vitro evaluation of substituted tetrahydroquinoline-isoxazole hybrids as anticancer agents
AbstractA series of isoxazole linked to 4-(2-oxopyrrolinidyl-1)-tetrahydroquinoline derivatives was efficiently synthesized. The synthetic route started with the formation of the correspondingN-propargyl tetrahydroquinoline derivatives via cationic Povarov reaction. Tetrahydroquinoline-isoxazole hybrid systems (3a–p) were obtained with good yields (42 –88%) through a 1,3-dipolar cycloaddition reaction with a click chemistry approach. These compounds have been tested for their in vitro cytotoxic activity against four different human cancer cell lines, lung (A549), liver (HepG2), and melanoma murine (B16F10) usin...
Source: Medicinal Chemistry Research - June 1, 2019 Category: Chemistry Source Type: research

In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus
AbstractTen 5-functionalized derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile were synthesized and their antiviral activities against the human cytomegalovirus (HCMV) were evaluated in vitro. Bioassays showed that seven compounds exhibited considerably higher antiviral activity (EC50:  30  µM and SI50:
Source: Medicinal Chemistry Research - May 31, 2019 Category: Chemistry Source Type: research

Antiplatelet activity and TNF- α release inhibition of phthalimide derivatives useful to treat sickle cell anemia
AbstractSickle Cell Anemia (SCA) is one of the most prevalent hereditary hematological diseases worldwide. The disease is characterized by chronic inflammation, hypercoagulable state, and pro-thrombotic profile, which lead the vaso-occlusive process. In this work, we described the antiplatelet activity and the ability to reduce tumor necrosis factor-alpha (TNF- α) levels of phthalimide derivatives. All compounds inhibited platelet aggregation induced by collagen and adenosine diphosphate, at levels ranging from 26.0 to 74.2% and 30.7 to 79.6%, respectively. The compounds exhibited reduced bleeding time compared to ac...
Source: Medicinal Chemistry Research - May 31, 2019 Category: Chemistry Source Type: research

Functional relaxant effect of 6,7-dipropoxy-2 H -chromen-2-one is mainly by calcium channel blockade in ex vivo assay of tracheal rings
In conclusion,6,7-DPC showed a relaxant effect due to combined mechanism of action on rat tracheal rings, through non-competitive muscarinic receptor functional antagonism and preventing the calcium influx. This provides pharmacological basis for the use of6,7-DPC in airways disorders, such as asthma or chronic obstructive pulmonary disease (COPD). (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - May 31, 2019 Category: Chemistry Source Type: research

Umbelliferone isolated from Zosima absinthifolia roots partially restored erectile dysfunction in streptozotocin-induced diabetic rats
In conclusion, intracavernosal administration of umbelliferone may prevent ED in diabetic rats by recovering of NO/cGMP pathway. These results m ay be supported by further studies using combinations of umbelliferone and phosphodiesterase type 5 inhibitors for the treatment of diabetic ED. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - May 31, 2019 Category: Chemistry Source Type: research

Green synthesis and 3D pharmacophore study of pyrimidine and glucoside derivatives with in vitro potential anticancer and antioxidant activities
AbstractA facile and an efficient one-pot green synthesis of pyrimidine derivatives using the environmentally friendly Cerium(IV) ammonium nitrate (CAN) as catalyst and water as a solvent has been described. Some of the synthesized pyrimidines react with 2,3,4,6-tetra-O-acetyl- α-d-glucopyranosyl bromide in ethanol containing potassium hydroxide to giveS-glucoside derivatives. The structures of the newly synthesized compounds were elucidated on the basis of their spectral and elemental analyses. In addition, selected derivatives of the products were screened for their anticancer activities against four tumor cell lin...
Source: Medicinal Chemistry Research - May 31, 2019 Category: Chemistry Source Type: research

Pyrazole –chalcone derivatives as selective COX-2 inhibitors: design, virtual screening, and in vitro analysis
In this study, a library of 300 pyrazole –chalcone derivatives were designed, the in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were evaluated, and a structure-based virtual screening was performed using AutoDock Vina. The docking results exhibited that the derivatives binding mode at the COX- 2 active site is similar to celecoxib, the reference drug, and presented similar binding energy. Six compounds were synthetized and tested for in vitro inhibition of the COX-1 and COX-2 isoenzymes and the selectivity index (SI) was calculated. The compound 2a11 showed the best activi...
Source: Medicinal Chemistry Research - May 30, 2019 Category: Chemistry Source Type: research

Quinoline analogs of 2-aminoindane as potential central dopaminergic agents
AbstractNeurodegenerative disorders such as Parkinson and Huntington Chorea are related with damage to the central dopaminergic system. On the purpose to find new drugs able to re-establish the imbalance on the dopaminergic neurotransmission in the central nervous system and counteract some of the neurodegenerative sicknesses, we have designed, synthesized, pharmacologically evaluated, and studied through molecular modeling,2-aminoindane-quinoline analog derivatives (1–5). Pharmacological studies made on the central nervous system through ICV (intracerebroventricular) and IS (intrastriatal), of compounds (1–5) ...
Source: Medicinal Chemistry Research - May 30, 2019 Category: Chemistry Source Type: research

Natural thiopeptides as a privileged scaffold for drug discovery and therapeutic development
AbstractSince the start of the 21st century, antibiotic drug discovery and development from natural products has experienced a certain renaissance. Currently, basic scientific research in chemistry and biology of natural products has finally borne fruit for natural product-derived antibiotics drug discovery. A batch of new antibiotic scaffolds were approved for commercial use, including oxazolidinones (linezolid, 2000), lipopeptides (daptomycin, 2003), and mutilins (retapamulin, 2007). Here, we reviewed the thiazolyl peptides (thiopeptides), an ever-expanding family of antibiotics produced by Gram-positive bacteria that ha...
Source: Medicinal Chemistry Research - May 29, 2019 Category: Chemistry Source Type: research

Aminoalkyl-substituted flavonoids: synthesis, cholinesterase inhibition, β-amyloid aggregation, and neuroprotective study
AbstractIn this manuscript, 17 aminoalkyl-substituted flavonoid derivatives were synthesized and their anticholinesterase, anti-beta-amyloid (A β) aggregation and neuroprotective activities were evaluated. The synthesized compounds were prepared through four-step reaction, started from the reaction between 2-hydroxyacetophenone and 4-methoxy benzaldehyde. Among the final compounds,6j displayed the best anti-butyrylcholinesterase activity (IC50 = 0.335 μM). Moreover, compound6i significantly protected PC12 neurons against H2O2-induced cell death. This compound could also inhibit acetylcholineste...
Source: Medicinal Chemistry Research - May 23, 2019 Category: Chemistry Source Type: research

Viridicatol and viridicatin isolated from a shark-gill-derived fungus Penicillium polonicum AP2T1 as MMP-2 and MMP-9 inhibitors in HT1080 cells by MAPKs signaling pathway and docking studies
In this study, we investigated the MMP inhibitory effect of viridicatol and viridicatin, two compounds extracted from shark-gill-derived fungusPenicilliumpolonicum AP2T1, on MMP-2 and -9 in vitro and in silico. The MTT assay showed that viridicatol and viridicatin had no cytotoxicity at a concentration of 50  µM on HT1080 human fibrosarcoma cells. In addition, the studies by gelatin zymography and Western blot analysis confirmed that the two compounds effectively inhibited the protein activities and expressions of MMP-2 and -9. Moreover, molecular docking studies simulated and clarified the interacti on betwee...
Source: Medicinal Chemistry Research - May 23, 2019 Category: Chemistry Source Type: research

Synthesis and bioassay of a new class of disubstituted 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles
AbstractA new class of aroylethenesulfonylmethyl styryl oxadiazoles/thiadiazoles/triazoles and arylsulfonylethenesulfonylmethyl styryl oxadiazoles/thiadiazoles/triazoles were synthesized from the synthetic intermediatesE-aroylethenesulfonylacetic acid methyl ester,E-arylsulfonylethenesulfonylacetic acid methyl ester and substituted cinnamic acids adopting conventional and ultrasonication methodologies. All the synthesized compounds were obtained in higher yields and in shorter reaction times in ultrasound irradiation method when compared with conventional method. The structures of all the compounds were characterized by IR...
Source: Medicinal Chemistry Research - May 22, 2019 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of novel indone derivatives as selective ER β modulators
AbstractTo reduce the endometrial toxicity and improve the efficacy of current selective estrogen receptor modulators used in breast cancer treatment by enhancing ER β selectivity, inspired by active resveratrol oligomer, a series of analogs (5a –f,6a –b,7a –d,8a –d) were designed, synthesized and biologically evaluated. Among them, the chiral indone analog (2R,3R)-8a exhibited best antiproliferative activity against both breast cancer cell lines (MDA-MB-231 and MCF-7) and better safety profile on uterus than tamoxifen. Analog (2R,3R)-8a demonstrated good binding affinity and selectivity toward...
Source: Medicinal Chemistry Research - May 17, 2019 Category: Chemistry Source Type: research

Structure-activity relationships of novel dithiocarbamates containing α,β-unsaturated ketone fragment as potent anticancer agents
AbstractBased on the structure of novel lead compound8 discovered by our group, systematic structural modification was carried out. A series of compound8’s derivatives were synthesized and evaluated for their activities against human non-small cell lung cancer cell line H460. Among them, twelve compounds showed significant proliferation inhibition activities with IC50 values
Source: Medicinal Chemistry Research - May 10, 2019 Category: Chemistry Source Type: research

Discovery of 7-bromo-1,4-dihydrothieno[3 ’,2’:5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as the potential epidermal growth factor receptors for tyrosine kinase inhibitors
AbstractSmall molecule tyrosine kinase inhibitors (TKIs) targeting at epidermal growth factor receptor (EGFR) in recent years have made great progress in the treatment of advanced non-small cell cancer (NSCLC). Although as the first-line treatment for sensitizing EGFR mutation-positive metastatic NSCLC, gefitinib has also behaved quite a lot of side effect and EGFR tolerance. Herein, a novel series of 7-bromo-1,4-dihydrothieno[3 ’,2’:5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives were designed and synthesized, and screened for their inhibitory activity on the EGFR high-expressing human lung adenocarcin...
Source: Medicinal Chemistry Research - May 10, 2019 Category: Chemistry Source Type: research

An overview of tubulin modulators deposited in protein data bank
AbstractMicrotubules are cytoskeletal polymers of tubulin and composed of α- and β-tubulin heterodimers, which are regarded as one of the most important, promising and successful targets for chemotherapeutic agents to treat cancer. With more and more tubulin-modulator co-crystal complex structures being solved, the mechanism of action (MOA) of microtubule targeting agen ts (MTAs) are well understood, which in turn inspired the development of more efficient tubulin modulators. By analyzing the reported tubulin modulators (most of them are inhibitors) that have been co-crystalized with tubulin and deposited in pro...
Source: Medicinal Chemistry Research - May 7, 2019 Category: Chemistry Source Type: research

Evidence for the involvement of opioid receptor in Ajuga chamaepitys action in chemical and thermal models of pain in BALB/c mice
AbstractAjuga chamaepitys is a small herbaceous annual or biannual plant that belongs to Lamiaceae family. It grows in Europe and Eastern parts of the Mediterranean. One of the ethno-pharmacological uses of this plant is its use as a painkiller. In the present experimental work, the antinociceptive effect of the methanolic extract ofA. chamaepitys collected from Jordan was investigated using chemical and thermal models of pain in mice.A. chamaepitys extract decreased significantly the number of writhes that were induced in mice by the injection of 1% acetic acid compared to negative control group. The inhibitory effect pro...
Source: Medicinal Chemistry Research - May 6, 2019 Category: Chemistry Source Type: research

Chiral amide derivatives of ricinoleic acid and 3-hydroxynonanoic acid synthesis and cytotoxic activity
AbstractA series of chiral ricinoleic and 3-hydroxynonanoic acid derivatives were synthesized in this study using various chemical and biochemical procedures. An effective method for preparation of methyl esters of 3-hydroxynonanoic acid from castor oil or methyl ricinoleate by ozonolysis and oxidation was developed. Simple, fast, and efficient procedures were applied to obtain different primary and secondary, cyclic and acyclic amides, including hydroxamic acids. Among 24 synthesized derivatives of ricinoleic and 3-hydroxynonanoic acids, i.e., methyl esters, amides, and hydroxamic acids, 16 compounds were obtained and des...
Source: Medicinal Chemistry Research - April 30, 2019 Category: Chemistry Source Type: research

Design, synthesis, bioactivity, and DFT calculation of 2-thiazolyl-hydrazone derivatives as influenza neuraminidase inhibitors
AbstractThree series of thiazolylhydrazone derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activity against influenza virus H1N1 in vitro. Compounds1 and2 were synthesized via the one-pot reaction and compound3 was synthesized in two steps. Pharmacological results showed that the majority of the target compounds1,2, and3 exhibited moderate-to-good influenza NA inhibitory activity. The NA inhibitory activity of the most active compound2g (IC50 = 7.12 μg/ml) is better than that of the lead compoundA. Molecular docking was performed to study the possible in...
Source: Medicinal Chemistry Research - April 30, 2019 Category: Chemistry Source Type: research

Synthesis and cytotoxic effects on pancreatic cancer cells of resveratrol analogs
In this study, a series of resveratrol analogs was synthesized and the effects on the viability of pancreatic cancer cell lines were evaluated. The new molecules were designed by removing the 3- and 5-OH groups of resveratrol, and by incorporating other substituents in 4-position, or by replacing the dihydroxybenzene with other aromatic systems. In all compounds the 4 ′-OH was kept unalterated. The effects of the compounds on cell viability were analyzed in three pancreatic cancer cell lines with distinct genetic profiles. Several compounds (e.g.,5,9, and12) exhibited improved cytotoxic activities as compared to the ...
Source: Medicinal Chemistry Research - April 29, 2019 Category: Chemistry Source Type: research

Synthesis and biological evaluation of ursolic acid derivatives containing an aminoguanidine moiety
AbstractThree series of ursolic acid derivatives containing an aminoguanidine moiety were designed, synthesized, and evaluated for anti-bacterial and anti-inflammatory activity. Some compounds displayed potent anti-bacterial activity against Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values in the range of 2 –64 µg/mL. Compounds3a,5a, and7l showed significant inhibitory activity against the Gram-positive bacterial strainStaphylococcus aureus RN 4220, the Gram-negative bacterial strainEs...
Source: Medicinal Chemistry Research - April 27, 2019 Category: Chemistry Source Type: research

Inhibition of melanin production by sesquiterpene lactones from Saussurea lappa and their analogues
This study was focused on the inhibition of the extracellular melanin content. The screening results revealed that onlyα-cyclocostunolide (2) showed notable inhibition of the melanin production, particularly the extracellular melanin content, with an IC50 value of 5.75  μM. In addition, structure-activity relationship (SAR) of 12 sesquiterpene lactone analogues with reference to their melanin inhibitory activity was also investigated. However, none of the analogues were found to show any significant melanin inhibitory activity. To the best of our knowledge the above study is the first SAR investigation invo...
Source: Medicinal Chemistry Research - April 23, 2019 Category: Chemistry Source Type: research

Oxidative stress induced apoptosis mediated anticancer activity of Rhus typhina fruits extract in human colon cancer
AbstractThe present work was tested the anti-proliferation activity ofRhus typhina fruits extract (RTFE) in HEK293 and HT-29 cells, and studied their underlying mechanisms through the analysis of oxidative stress and apoptosis-related genes expressions by flow cytometer and RT-qPCR. In addition, the bioactive constituents were identified from RTFE by chromatography and NMR analysis. Among the various type of the fractions from the RTFE, the ethyl acetate fraction (EAF) was showed the potent anti proliferation effect in HT-29 cells. Thus EAF was selected for the further extensive analysis. Cytotoxcity and RT-qPCR results re...
Source: Medicinal Chemistry Research - April 22, 2019 Category: Chemistry Source Type: research

Oxindole-based chalcones: synthesis and their activity against glycation of proteins
AbstractDiabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a major role in the onset of late diabetic complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular diseases. There is a need to establish potential therapeutic regimens that can effectively inhibit the formation of AGEs. To this end a series of novel oxindole-based chalcones have been investig...
Source: Medicinal Chemistry Research - April 22, 2019 Category: Chemistry Source Type: research

Lappaconitine sulfate induces apoptosis in human colon cancer HT-29 cells and down-regulates PI3K/AKT/GSK3 β signaling pathway
AbstractLappaconitine (LA), a diterpenoid alkaloid extracted from the roots ofAconitum sinomontanum Nakai, possesses strong central analgesic, local anesthetic, antifebric and anti-inflflammatory effect. Lappaconitine hydrobromide (LH) is used clinically to treat analgesia, but its clinical application is limited because of its poor solubility in water. Studies have suggested that lappaconitine sulfate (LS) is a promising pain reliever, and this particular form not only has readily water soluble, but also exhibits anti-cancer effects. However, the mechanism of LS anti-cancer activity is poorly understood. The aim of this s...
Source: Medicinal Chemistry Research - April 22, 2019 Category: Chemistry Source Type: research

3D-QSAR modeling of Phosphodiesterase-5 inhibitors: evaluation and comparison of the receptor- and ligand-based alignments
AbstractPhosphodiesterase-5 (PDE5) inhibitors can be used as clinical agents for the treatment of erectile dysfunction and pulmonary hypertension. A series of aryl-chromeno-pyrrol derivatives were previously identified as PDE5 inhibitors in our lab. Herein, these molecules were subjected to 3D-QSAR analysis with CoMFA and CoMSIA methods to gain deeper insight into the structural requirements for their bioactivities. Receptor- and ligand-based alignment were used and compared to find the alignment-related factors that affect the accuracy of QSAR models. The receptor-based CoMFA and CoMSIA models, which were generated by sup...
Source: Medicinal Chemistry Research - April 16, 2019 Category: Chemistry Source Type: research