Rational design, synthesis and biological evaluation of novel 2-(substituted amino)-[1,2,4]triazolo[1,5-a]pyrimidines as novel tubulin polymerization inhibitors

Novel indolyl 1,2,4-triazole derivatives as potential anti-proliferative agents: in silico studies, synthesis, and biological evaluation

“…The choice of an indole/triazole moiety was supported by extensive research into heterocyclic compounds and their role in cancer therapy. [14][15][16] Their pharmacophore was found to be built out of a head (the heterocyclic moiety) which is essential for binding in the hydrophobic pocket of the receptor, a linker that forms a necessary hydrogen bonding interaction at the hinge region and a tail that extends to the solvent region. [17][18][19][20][21][22] We adopted this design in the new indole derivatives in which we also decided on a head, linker and a tail moiety.…”

Recognition of arylmethylidene derivatives of imidazothiazolotriazinones as novel tubulin polymerization inhibitors

“…Tubulin proteins are well-verified targets for anticancer therapy. 4–10 Microtubules consisting of tubulin polymers are involved in cell growth, division, motility, and intracellular transport. 10–13 Microtubule-targeting agents interfere with tubulin polymerization/depolymerization processes, disrupt the process of cell division, evoke cell cycle arrest, and eventually lead to cell apoptosis.…”

“…4–10 Microtubules consisting of tubulin polymers are involved in cell growth, division, motility, and intracellular transport. 10–13 Microtubule-targeting agents interfere with tubulin polymerization/depolymerization processes, disrupt the process of cell division, evoke cell cycle arrest, and eventually lead to cell apoptosis. 14–17 Known tubulin polymerization inhibitors vinblastine, 18 rhizoxin, 19 colchicine, 20 and combretastatin A-4 21 are presented in Fig.…”

Discovery of novel tubulin CBSI (R)-9k from the indanone scaffold for the treatment of colorectal cancer

“…1, have shown better comprehensive biological profiles in the field of overcoming multi-drug resistance, avoiding allergic reactions, destroying tumor blood vessels, and exhibiting proper pharmacokinetics and water-solubility. [15][16][17][18][19][20][21][22] Although a few CA-4 derivatives presented remarkable inhibitory activity against colorectal cancer cell xenograft models in preclinical studies, none of them were advanced to the clinical development for colorectal cancer therapy. [23][24][25] Due to the limited research in anti-CRC agents, particularly the serious drug resistance and toxicity from the approved microtubule targeting agents, discovering anti-colorectal cancer CBSIs in a novel scaffold is still a prevailing topic in the current research community.…”