Thiazole-Based Thiosemicarbazones: Synthesis, Cytotoxicity Evaluation and Molecular Docking Study

Area of Science:

• Medicinal Chemistry
• Drug Design
• Oncology

Background:

• Hybrid drug design offers a strategy to overcome pharmacokinetic limitations of conventional anticancer agents.
• Thiazole-thiophene hybrids have demonstrated notable anticancer properties in previous studies.
• Dysregulation of Mammalian Rab7b protein, involved in endosomal trafficking, is linked to malignant cell differentiation and cancer progression.

Purpose of the Study:

• To synthesize and evaluate novel thiazole derivatives for anticancer activity.
• To investigate the potential of these compounds as inhibitors of the Rab7b protein.
• To explore the in silico pharmacokinetic and toxicity profiles of the synthesized compounds.

Main Methods:

• Synthesis of novel thiazole derivatives using 1-(4-Methyl-2-(2-(1-(thiophen-2-yl) ethylidene) hydrazinyl) thiazol-5-yl) ethanone as a building block.
• Antitumor activity evaluation against MCF-7 tumor cells via MTT assay.
• Molecular docking studies with the Rab7b protein and in silico ADMET prediction using the admetSAR tool.

Main Results:

• Compounds 9 and 11b exhibited promising in vitro anticancer activity, with IC50 values of 14.6 ± 0.8 µM and 28.3 ± 1.5 µM, respectively, comparable to Cisplatin.
• Molecular docking indicated favorable interactions of the synthesized compounds within the Rab7b binding site.
• The study identified 17 novel synthetic thiazole compounds with potential as anticancer drug candidates.

Conclusions:

• Compounds 9 and 11 display significant anticancer potential, serving as promising lead compounds.
• These novel thiazole derivatives may offer a new avenue for developing anticancer agents to address chemo-resistance.
• The findings support the development of thiazole-based hybrids as novel anticancer therapeutics targeting Rab7b.