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In Vitro Anticancer Properties of Novel Bis-Triazoles.

ABSTRACT: Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI₅₀ and LC₅₀ values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA.

SUBMITTER: Saleh MM

PROVIDER: S-EPMC9858002 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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<i>In Vitro</i> Anticancer Properties of Novel Bis-Triazoles.

Saleh Maysaa M MM Abuarqoub Duaa A DA Hammad Alaa M AM Hossan Md Shahadat MS Ahmed Najneen N Aslam Nazneen N Naser Abdallah Y AY Moody Christopher J CJ Laughton Charles A CA Bradshaw Tracey D TD

Current issues in molecular biology 20221229 1

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. ...[more]

PMID: 36661500

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Project description:IntroductionHeterocyclic compounds have diverse biological activities and potential in drug development. This study aims to synthesize novel compounds with two 1,2,4-triazole cores and evaluate their biological properties, particularly their inhibitory activity against thymidine phosphorylase (TP), an enzyme involved in various physiological processes.MethodsThe compounds were synthesized by reacting 5,5'-butane-bis-1,2,4-triazole derivatives with prenyl bromide. Characterization involved various techniques, including spectroscopy and elemental analysis. Antimicrobial potential was evaluated against bacteria and fungi, with comparative antibiotics as references. Inhibitory activity against TP was assessed, and molecular docking studies were conducted.ResultsSix compounds were successfully synthesized and their structures confirmed. The synthesized triazole derivatives exhibited high biological activity, with compounds 2 and 6 showing the most promising TP inhibition. Molecular docking studies revealed interactions between compound 2 and TP, involving nine amino acids.DiscussionThe synthesis of novel compounds with two 1,2,4-triazole cores contributes significantly to bis-triazole research. These compounds have potential as anti-tumor agents due to their inhibitory activity against TP, a crucial enzyme in tumor growth and metastasis. Comparative evaluation against antibiotics highlights their potency. Docking results provide insights into their interactions with TP, supporting their potential as potent TP inhibitors. Further research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and optimizing their activities.ConclusionThe synthesized compounds with two 1,2,4-triazole cores exhibit significant biological activity, including strong TP inhibition and broad-spectrum antimicrobial effects. These findings emphasize their potential as anti-tumor agents and the need for further exploration and optimization. Future research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and developing more potent bis-triazole derivatives for drug discovery efforts. The combined results from assays and docking studies support the therapeutic potential of these compounds as anti-tumor agents.

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In Vitro Anticancer Properties of Novel Bis-Triazoles.

Publications

<i>In Vitro</i> Anticancer Properties of Novel Bis-Triazoles.

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