Synthesis and cytotoxicity of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives bearing 3,4,5-trimethoxyphenyl moiety

Zhao, Pei‐Liang; Duan, An-Na; Zou, Min; Yang, Hai‐Kui; Wang, You; Wu, Shuai

doi:10.1016/j.bmcl.2012.03.023

Cited by 34 publications

(11 citation statements)

References 21 publications

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“…the most effective compound was able to arrest the cell growth of A549, AGS (gastric cancer), and PC‐3 (prostate cancer) by IC 50 value of 3.99, 0.13, and 0.51 μ m , respectively . Determination of the cytotoxic activity of a new series of 3,4‐disubstituted‐5‐(3,4,5‐trimethoxyphenyl)‐4 H ‐1,2,4‐triazoles (as combretastatin analogs) revealed that the most active compound was able to inhibit HT‐29, MCF‐7, and HepG2 cell lines by the IC 50 values of 126.40, 63.72, and 31.72 μ m , respectively …”

Section: Resultsmentioning

confidence: 96%

“…Combretastatin A‐4 (CA‐4; Figure ), a natural product originated from the bark of South African willow tree Combretum caffrom , belongs to the family of microtubule targeting agents (MTA) which exhibits strong growth suppression toward a wide range of human tumors including multidrug resistant (MDR) cancer at nanomolar concentrations . During the two last decades many structure–activity relationship (SAR) studies have been performed to synthesize more potent analogs of CA‐4 by modification or derivatization of C=C bond, or the aromatic rings A and B ( Figure ) …”

Section: Introductionmentioning

confidence: 99%

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Hybrid Pharmacophore Design, Molecular Docking, Synthesis, and Biological Evaluation of Novel Aldimine‐Type Schiff Base Derivatives as Tubulin Polymerization Inhibitor

Ameri

Khodarahmi

Forootanfar

et al. 2018

Chemistry & Biodiversity

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A series of hybrid aldimine-type Schiff base derivatives including trimethoxyphenyl ring and 1,2,4-triazole-3-thiol/thione were designed as tubulin inhibitors. The molecular docking simulations on tubulin complex (PDB: 1SA0) revealed that derivatives with nitro and/or chloro or dimethylamino substitutes (4-nitro, 2-nitro, 3-nitro, 4-Cl-3-nitro, and 4-Me N) on the aldehyde ring were the best compounds with remarkable binding energies (-9.09, -9.07, -8.63, -8.11, and -8.07 kcal mol , respectively) compared to colchicine (-8.12 kcal mol ). These compounds were also showed remarkable binding energies from -10.66 to -9.79 and -10.12 to -8.95 kcal mol on human (PDB: 1PD8) and Candida albicans (PDB: 3QLS) DHFR, respectively. The obtained results of cytotoxic activities against HT1080, HepG2, HT29, MCF-7, and A549 cancer cell lines indicated that 4-nitro and 2-nitro substituted compounds were the most effective agents by mean IC values of 11.84 ± 1.01 and 19.92 ± 1.36 μm, respectively. 4-Nitro substituted compound (5 μm) and 2-nitro substituted compound (30 μm) were able to strongly inhibit the tubulin polymerization compared to colchicine (5 μm) and 4-nitro substituted compound displayed IC values of 0.16 ± 0.01 μm compared to that of colchicine (0.19 ± 0.01 μm). This compound also showed the lowest MIC values on all tested microbial strains including three Gram-positive, four Gram-negative, and three yeast pathogens.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Hybrid Pharmacophore Design, Molecular Docking, Synthesis, and Biological Evaluation of Novel Aldimine‐Type Schiff Base Derivatives as Tubulin Polymerization Inhibitor

Ameri

Khodarahmi

Forootanfar

et al. 2018

Chemistry & Biodiversity

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“…Moreover, 1,2,4-triazole nucleus has been previously emerged as promising lead to develop anti-cancer scaffolds (Kaczor et al, 2013;Zhao, 2012;Kumar et al, 2011). In this study, newer 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines bearing different heteroaryls in their core structure were yielded via efficient chemical synthesis strategies.…”

Section: Resultsmentioning

confidence: 99%

Studies of in vitro anti-prostate cancer potential of newer 1,2,4-triazolo-1,3,4-thiadiazines with different heteroaromatics

Fan

Han

Zhang

et al. 2015

Bangladesh J Pharmacol

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This study was aimed to evaluate anticancer potential of newer synthesize 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines and its derivatives. All newly furnished scaffolds were subjected to screening for their in vitro anticancer potential against DU-145 and PC-3 prostate cancer cell lines using SRB and MMT bioassays. The structures of final compounds were confirmed with the aid of FT-IR, 1H NMR, 13C NMR spectroscopy and CHN analysis. Bioassay studies suggested that all thiadiazines were promising cytotoxic agents with % cytotoxicity ranging from 44.39-71.24%, whereas potent GI50 level in the range 11.96-32.51 µg/mL and results were comparable to the potencies of control drugs adriamycin and doxorubicin. Variation of heterocyclic pharmacophores along with the C-5 position of 1,2,4-triazole in terms of quinoline, quinazoline, coumarin and pyridine lead to the different SAR predictions in which quinoline and benzimidazole moieties found most promising.

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“…Encouraged by these results and as a part of our research work on the development of novel scaffolds with anticancer activity , we developed an idea that introducing aminopyrimidine moiety with a piperazine ring into the C3 position of the indole scaffold might result in new compounds with high cytotoxic activity. Herein, we described the synthesis and biological activity of a series of novel hybrids of indole–pyrimidine‐containing piperazine moiety 16 – 34 (Scheme ), which have, to our knowledge, not been reported so far.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Molecular Docking Studies of Novel Indole–Pyrimidine Hybrids as Tubulin Polymerization Inhibitors

Zhang

Yang

et al. 2015

Chem Biol Drug Des

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A series of novel hybrids of indole-pyrimidine-containing piperazine moiety were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. The results indicated that most of these compounds possessed significant cytotoxic potency against four cancer cell lines, HT-29, A549, MDA-MB-231 and MCF-7. Particularly, the most promising compound 34 showed more potent and broad-spectrum cytotoxic activities with the IC50 values ranged from 5.01 to 14.36 μm against A549, MDA-MB-231 and MCF-7 cell lines. Meanwhile, 34 also displayed the most potent tubulin polymerization inhibitory activity with IC50 value of 11.2 μm. Furthermore, molecular docking analysis demonstrated 34 interacts and binds efficiently with the tubulin protein at the colchicine-binding site. It was worth noting that the compound did not affect the normal human embryonic kidney cells, HEK-293. These results suggest that this novel class of indole-pyrimidine hybrids may have potential to be developed as new a class of tubulin polymerization inhibitors.

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Synthesis and cytotoxicity of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives bearing 3,4,5-trimethoxyphenyl moiety

Cited by 34 publications

References 21 publications

Hybrid Pharmacophore Design, Molecular Docking, Synthesis, and Biological Evaluation of Novel Aldimine‐Type Schiff Base Derivatives as Tubulin Polymerization Inhibitor

Hybrid Pharmacophore Design, Molecular Docking, Synthesis, and Biological Evaluation of Novel Aldimine‐Type Schiff Base Derivatives as Tubulin Polymerization Inhibitor

Studies of <i>in vitro</i> anti-prostate cancer potential of newer 1,2,4-triazolo-1,3,4-thiadiazines with different heteroaromatics

Design, Synthesis and Molecular Docking Studies of Novel Indole–Pyrimidine Hybrids as Tubulin Polymerization Inhibitors

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