New triazole derivatives containing substituted 1, 2, 3-triazole side chains: Design,synthesis and antifungal activity

In order to discover new generation of triazole antifungal agents,a series of novel antifungal triazoles were designed and synthesized by structural simplification of our previously identified triazole-piperdine-heterocycle lead compounds.Several target compounds showed good antifungal activity with a broad spectrum.In particular,compound 7l was highly active against Candida albicans and Candida glabrata.Moreover,compound 7l showed potent in vivo antifungal efficacy in the Caenorhabditis elegans-C.albicans infection model.     

Design, synthesis and anti-proliferative studies of a novel series of indirubin derivatives

<正>A series of novel derivatives of indirubin were synthesized and evaluated for their anti-proliferative activity against human cancer cell lines of SGC7901,A549,HL-60,SK-BR-3 and HCT116.Most of the compounds displayed more potent activity than Sunitinib.In addition,the derivatives showed improved water solubility,which may be favorable to their pharmacokinetic performances.     

Design,synthesis, and biological evaluation of diarylpyrazole derivatives as antitumor agents targeting microtubules

A new series of novel diarylpyrazole derivatives as microtubule destabilizers were synthesized and evaluated for the anti-proliferative activities. Anti-proliferative assays were performed on the human cervix adenocarcinoma cell line (HeLa) and human gastric adenocarcinoma cell line (SGC-7901), and the compound 9s containing indole ring showed great anti-proliferative activity against HeLa cells with IC₅₀ value of 1.9 ± 0.11 μM. Further biological studies showed that 9s was able to inhibit tubulin polymerization, disrupt the cytoskeleton, block the cell cycle in the G2/M phase, and induce cell apoptosis in a concentration-dependent manner. In addition, the results of molecular docking studies showed that compound 9s could bind tightly to the colchicine binding site of tubulin through hydrogen bonding interaction. These preliminary results recommend that compound 9s is likely to be a microtubule destabilizer that deserves further investigation.     

Design,synthesis and anti-proliferative effects in tumor cells of new combretastatin A-4 analogs

A total of 11 novel combretastatin A-4(CA-4) analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes:(i)hydrogenated derivatives,(ii) ethoxyl derivatives,(iii) amino derivatives and(iv) pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure–activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study.     

1,2,3-triazole derivative: Synthesis,characterization, DFT,molecular docking study and antibacterial-antileishmanial activities

In this study, 4-((1-(4-chlorobenzyl)-1H-1,2,3-triazole-4-yl)methoxy)-3-methoxybenzaldehyde (I) was synthesized and molecular structure of compound I was confirmed by FTIR and NMR (¹H and ¹³C NMR) spectroscopic methods. The geometric structure of compound I was optimized by DFT/B3LYP method using 6–311++G(d, p) basis set. The molecular docking study was carried out against six different proteins. The antibacterial and antileishmanial activities of compound I were tested by microdilution broth with Alamar blue method and minimum inhibitor concentrations (MIC) were determined. According to the test results, it was found to be effective against eleven types of bacteria at different concentrations (MIC: 312–5000 ​μg/mL). In addition, compound I was not effective against leishmania species at the concentrations that were examined.     

Design,synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains

In order to explore novel antifungal agents, twenty-seven triazole derivatives featuring an alkyne linker in the side chain were designed and synthesized by the Sonogashira reaction. Most of the target compounds exhibited good antifungal activity against eight human pathogenic fungi, especially excellent activity against Candida and Cryptococcus species, comparing with the reference drugs fluconazole, voriconazole and ravuconazole. Compounds A2 and A3 exhibited in vitro activity against all the tested fungi with MIC₈₀ values ranging from 0.0156 μg/mL to 0.5 μg/mL, which are superior to ravuconazole and fluconazole. SAR and molecular docking study give a clear conclusion that para-fluoro, para-chloro, and para-cyano substituted phenylalkynyl or pyridinylalkynyl side chains may promote triazole antifungal activity.     

Design,synthesis and anti-diabetic activity of chromen-2-one derivatives

DPP-IV inhibitors have been immersed as promising pathway to treat Type 2 diabetes. Here we have reported designing of coumarin derivatives as DPP-IV inhibitors. Designed compounds have been studied for their binding with DPP-IV enzyme through molecular docking followed by synthesis. All synthesized compounds have been fully characterized and screened for DPP-IV inhibition activity. Two compounds showed very good inhibition at 10 μM concentration.     

Design and synthesis of new carbohydrate-lithocholic acid conjugates linked via 1,2,3-triazole rings

In this work, we report the synthesis of a novel carbohydrate-lithocholic acid conjugate linked through of 1,2,3-triazole rings and its derivatives in good to excellent yields. The conjugate was synthesized via copper-catalyzed azide?alkyne cycloaddition (CuAAC) from methyl 4,6-O-benzylidene-2,3-di-O-propargyl-α-d-glucopyranoside and methyl 3-azidolithocholate. The structures of all new compounds were properly characterized by infrared (IR), high-resolution mass spectroscopy (HRMS) and one- and two-dimensional nuclear magnetic resonance (NMR).     

Design,synthesis and antimicrobial activities of 1,2,3-triazole derivatives

Fifteen 1-(4-substituted phenyl)-4-(4-bromophenyl)-5-(halo-o-hydroxyphenyl)imino-1,2,3-triazoles were designed and synthesized based on rational combination of 1,2,3-triazoles and(halo)o-hydroxyphenyl group according to the superposition principle of reinforcement of biological activities.All the compounds were tested to an in vitro antimicrobial screening against M.a.and E.c..Compounds IIe-IIo exhibited more potent antimicrobial activities against M.a.and E.c.than triclosan and fluconazole,which provided valuable information to further study of novel antimicrobial research.     

Synthesis, Structure and Biological Activities of 2-（1H- 1,2,3-Benzotriazol-1 -yl ）-1-（ 4- methylphenyl ）-2-（1H-1,2,4-triazol-l-yl）-1-ethanone

The title compound was synthesized and characterized by IR, ^1H NMR, elemental analysis and single crystal X-ray diffraction analysis. Its biological activities were also tested. The results show that the title compound reveals inhibiting activities towards wheat gibberellin, apple ringspot, tomato early blight, peanut cercospora arachidicola and stem wilt of asparagus.     

Synthesis,Structure and Biological Activities of 2-(1H- 1,2,3-Benzotriazol-1-yl)-1-(4-methylphenyl)-2- (1H-1,2,4-triazol-1-yl)-1-ethanone

IntroductionTriazole derivatives have become the most rapidlyexpanding group of antifungal compounds with advanta-ges of lowtoxicity, high oral bioavailability and broad-spectrum antifungal activity, which can be used againstfungi including most yeasts an…     

Syntheses, Structure and Biological Activities of 2-（ 1H-Benzo [ 1,2,3 ] triazole-l-yl） -1-（3-methyl-4-bromobiphenyl） - 2- （ 1H-1, 2,4-triazole-1 -yl ） ethanone

Introduction 1,2,4-Triazole derivatives represent an interesting class of heterocyclic compounds[1] and have become the most rapidly expanding group of antifungal compoundswith the advantages of toxicity, high oral bioavailability, and broad spectrum of activity against several fungi, including most yeasts and folanentous fungi[2-4].     

Synthesis and in vitro anti-proliferative capabilities of steroidal thiazole and indole derivatives

Derivatives (1–15) of steroidal and indole class were synthesized using different strategies. These compounds were characterized by ¹H NMR spectroscopy and EI-MS, respectively. The synthetic derivatives were examined for their cytotoxic effects on human adenocarcinoma cells (HCT-116) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and morphometric analysis. The cytotoxic effects of all the compounds were observed after 48 h treatment and it was found that out of fifteen, four compounds 1, 2, 3, and 14 showed inhibitory action on the cancer cells. We have calculated the IC₅₀ values for compounds 1, 2, 3, and 14 which were 22.50 µg/mL, 55.65 µg/mL, 21.35 µg/mL and 58.50 µg/mL, respectively. The compounds 3 (IC₅₀ = 21.35 µg/mL) and 1 (IC₅₀ = 22.50 µg/mL) showed highest inhibitory activities as compared to compounds 2 (IC₅₀ = 55.65 µg/mL) and 14 (IC₅₀ = 58.50 µg/mL). These results suggested that steroidal thiazole and indole derivatives are potent lead molecules having strong anti-cancer proliferative capabilities.     

Design,synthesis, and anticancer activity evaluation of novel aziridine-1,2,3-triazole hybrid derivatives

Some new 1-aryl-4-[(aziridine-1-yl)diaryl-methyl]-5-methyl-1H-1,2,3-triazole derivatives 7j–s were synthesized by the one-pot reaction of diaryl-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)methanol compounds 6j–s formed from 1-aryl-5-methyl-1H-1,2,3-triazole-4-carboxylic acid derivatives. The new compounds 7j–s and 6j–s are investigated by ¹H and ¹³C NMR, MS, and IR. The anticancer activity of the synthesis target compounds was evaluated against human leukemia (HL-60) cells and human hepatoma G2 cells. Some of the compounds were highly efficient. The ¹H-NMR signals of the aziridine-ring cis-H/trans-H protons were found to be two group peaks at 1.800–1.884 and 1.183–1.327?ppm.     

Synthesis,spectral characterization,molecular docking studies,biological activity of (E)-2-((E)-3-(3,4,5-trimethoxyphenyl)allylidene) and (E)-N-phenyl 2-((E)-3-(3,4,5-trimethoxyphenyl)allylidene)hydrazinecarbothioamides and their Cu(II) complexes

Two slightly distorted octahedral complexes of copper(II) with (E)-2-((E)-3-(3,4,5-trimethoxyphenyl)allylidene)hydrazinecarbothioamide (L1) common name 3,4,5-trimethoxy-cinnamaldehydethiosemicarbazone and (E)-N-phenyl-2-((E)-3-(3,4,5-trimethoxyphenyl)-allylidene)hydrazinecarbothioamide (L2) common name 3,4,5-trimethoxycinnamaldehyde-4-phenylthiosemicarbazone have been synthesized. The two free ligands and their copper(II) complexes were characterized by spectroscopic techniques like FT-IR, FT-Raman, UV, EPR, Powder X-ray diffraction and cyclic voltammetry. The EPR spectra evidenced a rhombically distorted octahedron geometry for both the copper(II) complexes. The band gap calculations for the ligands L1, L2 and their complexes Cu(L1)₂Cl₂ and Cu(L2)₂Cl₂ were found to be 2.98, 2.61, 2.66 and 2.50 eV respectively. Cu(L1)₂Cl₂ and Cu(L2)₂Cl₂ have shown 50% of viability at 80 μg/ml and 60 μg/ml. The anti-oxidant activity study revealed that the compounds are good reductants of DPPH radical. Moderate to good anti-bacterial activity is shown by the compounds against the Gram-positive and Gram-negative bacteria. Molecular docking studies have been carried out to predict the orientation and binding mode of analysis in the active site. The synthesized ligand and complex well occupy (catalytic triad and adenine-binding site) in the active site of β-ketoacyl-acyl carrier protein synthase III enzyme, and also well occupy in helix 11 (in the DCS complex) of human estrogen receptor. Moreover they form water mediated hydrogen bond and hydrogen bond with Cys530 residue.     

Rhodium-catalysed synthesis of fused pyrimidine derivatives employing N-sulfonyl-1,2,3-triazoles as a 1-aza-[4C] synthon

A new synthetic application of N-sulfonyl-1,2,3-triazoles acting as a 1-aza-[4C] synthon via the 1,2-shift reaction of an α-imine rhodium carbene was developed for the synthesis of fused pyrimidine derivatives. The high reactivity of the strained three-membered 2H-azirine ring facilitated the unusual cyclization of electron-deficient dienes with electron-deficient dienophiles. The compatibility was good with common functionalities tolerated. Excellent chemoselectivity was observed, and no reactions occurred between the rhodium carbene and 2H-azirine. The products could be converted into seven-membered multi-functionalized 1H-1,4-diazepine derivatives, illustrating the potential application of the protocol in medium-sized N-heterocycle synthesis.     

Novel efficient anticancer agents and DNA-intercalators of 1,2,3-triazol-1,8-naphthalimides: design, synthesis, and biological activity

Two novel series of 3-1,2,3-triazol-1,8-naphthalimides 5a-e, 7a-e were synthesized easily by employing ‘click reaction’. Their bioactivities were evaluated. Compounds 5a-e were found to be more toxic against MCF-7 cells while 7a-e were more potent against 7721 cells, in particular 7a, the IC₅₀ value of which against cell lines of MCF-7 and 7721 was 0.348 μM and 0.258 μM, respectively. Due to the phenyl group linked to 1,2,3-triazole, compound 5a not only showed higher DNA affinity but also more efficient DNA damaging ability than compound 7a.     

Design,synthesis and antiviral activities of chalcone derivatives containing pyrimidine

A series of chalcone derivatives (T1-T23) containing pyrimidine were synthesized, characterized, and assessed for their antiviral activity against tobacco mosaic virus (TMV) activities. Most target compounds displayed better antiviral activities against TMV than commercial ningnanmycin. Among them, the EC₅₀ value of curative activities of compounds T1, T7, T9 and T19 (219.2, 228.2, 279.9 and 234.9 μg/mL, respectively) were superior to that of ningnanmycin (320.1 μg/mL). In addtion, the EC₅₀ value of protective activities of compounds T5, T9, T19 and T23 (235.0, 220.0, 199.5 and 187.2 μg/mL, respectively) were superior to that of ningnanmycin (307.4 μg/mL). Then, the antiviral mechanism of T19 and TMV coat protein (TMV-CP) was preliminarily investigated by microscale thermophoresis (MST) and molecular docking technology. The results showed that T19 had a strong binding affinity for TMV coat protein, and its dissociation constant (K_d) was 0.00310 ± 0.000916 μM, which was superior to ningnanmycin(0.165 ± 0.0799 μM). This study suggests that chalcone derivatives containing pyrimidine could be used as novel antiviral agents for controlling the plant viruses.     

Amide derivatives of 4-azaindole: Design,synthesis, and EGFR targeting anticancer agents

Abstract

A series of amide derivatives of azaindole-oxazoles (11a-n) were designed and synthesized and their structures were confirmed by ¹HNMR, ¹³CNMR and mass spectral analysis. Further, these derivatives were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC₅₀ values 0.034 and 0.036?µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC₅₀ values.