Anticancer ۱,۳-thiazole Derivatives: In Vitro Evaluation and in Silico Tubulin/Lipoxygenase Inhibition

Background: Addressing cancer treatment and drug resistance is critical because cancer remains a leading cause of death worldwide. Targeting key enzymes, such as tubulin and lipoxygenase, may yield new strategies to impede tumor growth and enhance treatment efficacy. Objectives: This study aimed to evaluate the anticancer effects of ۱,۳-thiazole derivatives on A۵۴۹ and HT-۲۹ cancer cell lines and investigate their ability to inhibit tubulin and lipoxygenase enzymes. Methods: Ethyl and methyl derivatives with a central ۱,۳-thiazole core were synthesized in one step. A۵۴۹ and HT-۲۹ cells were cultured in RPMI ۱۶۴۰ medium. The cytotoxic effects of the derivatives were assessed by treating the cells with varying concentrations for ۲۴, ۴۸, and ۷۲ hours, followed by ۳-(۴,۵-dimethylthiazol-۲-yl)-۲,۵-diphenyltetrazolium bromide (MTT) assays. Molecular docking using AutoDock Vina software, version ۱.۱.۲ was performed to evaluate the derivatives’ inhibitory effects on tubulin and lipoxygenase. Results: Compound A demonstrated significant anticancer activity against A۵۴۹ cells at ۵۰۰ µg/mL. Compound B also inhibited ۵۰% of cancer cells at ۱۰۰۰ µg/mL. In the HT-۲۹ cell line, compound A reduced cell viability by ۵۰% at ۵۰۰ µg/mL, while compound B showed stronger effects at the same concentration. Ligand A exhibited notable inhibitory potential against tubulin, whereas ligand B had significant inhibitory effects against tubulin and lipoxygenase. Conclusion: The ethyl substituent of the ۱,۳-thiazole core shows promise as an anticancer agent against A۵۴۹, while the methyl substituent is effective against HT-۲۹. Both derivatives can inhibit tubulin function.

کلیدواژه ها:

Thiazoles ، A۵۴۹ cells ، HT-۲۹ cells ، Tubulin ، Lipoxygenase ، Molecular docking