Design, synthesis and bio-evaluation of novel 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazoles as the tubulin polymerization inhibitors

“…Compound 5 exhibited potent antiproliferative potency against a panel of cancer cell lines with a mean GI 50 value of 3.3 nM and potent inhibitory effect on tubulin polymerisation by acting on the colchicine binding site. Compound 6 posing a N -acyl-piperazine moiety, as the tubulin polymerisation inhibitor, showed significant antiproliferative activities against SGC-7901, A549, and Hela cells (IC 50 values of 0.084–0.221 μM) 31 . In addition, arylpiperazinyl oxazole 7 exhibited potent anticancer effects in vitro and in vivo by the inhibition of tubulin polymerisation and excellent vascular-disrupting activity 32 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of novel arylamide derivatives containing piperazine moiety as inhibitors of tubulin polymerisation with potent liver cancer inhibitory activity

Shi,

Jiao,

Zhang

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this work, a series of novel arylamide derivatives containing piperazine moiety were designed and synthesised as tubulin polymerisation inhibitors. Among 25 target compounds, compound 16f ( MY-1121 ) exhibited low nanomolar IC 50 values ranging from 0.089 to 0.238 μM against nine human cancer cells. Its inhibitory effects on liver cancer cells were particularly evident with IC 50 values of 89.42 and 91.62 nM for SMMC-7721 and HuH-7 cells, respectively. Further mechanism studies demonstrated that compound 16f ( MY-1121 ) could bind to the colchicine binding site of β-tubulin and directly act on β-tubulin, thus inhibiting tubulin polymerisation. Additionally, compound 16f ( MY-1121 ) could inhibit colony forming ability, cause morphological changes, block cell cycle arrest at the G2 phase, induce cell apoptosis, and regulate the expression of cell cycle and cell apoptosis related proteins in liver cancer cells. Overall, the promising bioactivities of compound 16f ( MY-1121 ) make the novel arylamide derivatives have the value for further development as tubulin polymerisation inhibitors with potent anticancer activities.

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“…Notably, it is well-established that the anti-tubulin agents that bind at the colchicine binding pocket of tubulin hold strong antitumor or anticancer potential [47, 78, 79, 70, 80]. These agents demonstrate high anticancer efficacy and minimal off-target interactions, with many currently progressing through various phases of clinical trials for cancer chemotherapy [81, 82].…”

Section: Discussionmentioning

confidence: 99%

3-epicaryoptin induces G2/M phase cell cycle arrest and apoptosis in human breast cancer cells by disrupting the microtubule network, anin vitroandin silicoinvestigation

Barman,

Roy,

Singh

et al. 2024

Preprint

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Breast cancer (BC) is a prevalent form of cancer observed in women across the globe, constituting over a quarter of all female BC cases. The treatment of BC continues to require significant efficacy, aiming to achieve high success rates while minimizing adverse effects on the body as a whole. In the current study, 3-epicaryoptin was tested for the molecular mechanism of its anti-cancer activity in the human breast cancer cell line, MCF-7. We investigated cell viability by MTT assay, cell cycle kinetics and apoptosis, immunofluorescence straining, molecular modelling, and ADMET profiling. MTT assay results showed that 3-epicaryoptin was found cytotoxic against MCF-7 cells with an IC50 value of 0.345 mg mL-1 for 48 h. Flow cytometric analysis exhibited that 3-epicaryoptin halted the MCF-7 cells in the G2/M phase and subsequently induced apoptosis in a time-dependent manner. Our immunofluorescence studies indicated that 3-epicaryoptin inhibited microtubule polymerization in MCF-7 cells. Furthermore, molecular docking followed by molecular dynamics (MD) simulation studies demonstrated the ability of 3-epicaryoptin to interact with the tubulin protein at the colchicine binding pockets. Overall, our results suggest that 3-epicaryoptin can inhibit the proliferation of human breast cancer cells by depolymerizing of cellular microtubule networks, which causes cell cycle arrest and promotes apoptotic cell death. Therefore, it has been indicated that the natural product 3-epicaryoptin exhibited considerable promise as a potent therapeutic agent capable of inducing apoptosis in breast cancer cells.

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Design, synthesis and bio-evaluation of novel 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazoles as the tubulin polymerization inhibitors

Cited by 17 publications

References 24 publications

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

Discovery of novel arylamide derivatives containing piperazine moiety as inhibitors of tubulin polymerisation with potent liver cancer inhibitory activity

3-epicaryoptin induces G2/M phase cell cycle arrest and apoptosis in human breast cancer cells by disrupting the microtubule network, anin vitroandin silicoinvestigation

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