Identification and characterisation of sertaconazole and tioconazole as potential anticancer agents with microtubule depolymerising activity based on in silico and in vitro analysis

Abstract

Cancer, the uncontrolled growth of cells in the body, is the second major cause of newlinehuman death in the world. Among many methods to treat cancer, chemotherapy is newlineconsidered as the most successful and widely used treatment strategy. Antimitotic agents, newlinewhich inhibit the growth of cancer cells at mitotic phase and induce apoptotic cell death, newlineattained great recognition as chemotherapy drugs for the treatment of cancer. Majority newlineof antimitotic agents interact with microtubules and interfere with the dynamics of newlinemicrotubules during mitotic cell division. The formation of mitotic spindle apparatus newlinethrough microtubule dynamics is considered to be essential for the segregation of newlinechromosomes during mitosis. The disruption of microtubule dynamics through newlinestabilisation or destabilisation of microtubules leads to mitotic arrest and cell death. The newlinedrugs that interact with microtubules generally bind at one of the three sites such as newlinevinblastine site, taxol site, or colchicine site. Colchicine binds to the interface of tubulin newlineheterodimer and induce the depolymerisation of microtubules. The colchicine binding newlinesite on tubulin is the much sought-after target in the history of anti-microtubule drug newlinediscovery. The antifungal benzimidazoles are reported to inhibit the growth of cancer newlinecells by inducing mitotic block and interfering with polymerisation of microtubules. newlineEconazole, miconazole, sertaconazole and tioconazole, the structurally related azoles newlinewith imidazole moiety, are known to be cytotoxic and they are clinically available only newlinefor topical application. newlineThe four structurally related azoles, econazole, miconazole, sertaconazole, and newlinetioconazole, were evaluated for their cytotoxic and antimitotic potential. The results newlineindicated econazole, miconazole, sertaconazole, and tioconazole inhibited the newlinexvi newlineproliferation of HeLa cells with an IC50 of 28, 98, 38 and 14 and#956;M respectively with newlinesertaconazole and tioconazole alone inducing a mitotic block in the treated cells.