2. Academic Validation
  3. New thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety as anticancer agents

New thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety as anticancer agents

  • Eur J Med Chem. 2020 Jan 1:185:111784. doi: 10.1016/j.ejmech.2019.111784.
Mahsa Ansari 1,  Mohammad Shokrzadeh 2,  Saeed Karima 3,  Shima Rajaei 3,  Marjan Fallah 2,  Nasrin Ghassemi-Barghi 2,  Majid Ghasemian 3,  Saeed Emami 4
Affiliations

Affiliations

  • 1 Pharmaceutical Sciences Research Center, Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 2 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 3 Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
  • 4 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: semami@mazums.ac.ir.
PMID: 31669850 DOI: 10.1016/j.ejmech.2019.111784
Abstract

A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with Anticancer activity. The cytotoxicity evaluation of synthesized compounds against Cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent cytotoxic activity toward all tested cell lines (IC50s < 10 μg/mL). Among them, 3-(chlorobenzyl) derivatives 5c and 5d showed the best inhibitory effect on MCF-7 cells (IC50 values of 1.14 and 2.41 μg/mL, respectively). Furthermore, the ability of tubulin polymerization inhibition and Apoptosis induction were evaluated for the promising compounds 5c and 5d. Results suggested that these compounds remarkably inhibit tubulin polymerization and induce Apoptosis resulting in cell death. In vitro studies revealed that these compounds had no significant cytotoxicity against normal cells at the concentrations required for growth inhibition of Cancer cells. In vitro biding assay and in silico docking study also confirmed the binding of prototype compound to the colchicine binding site of tubulin.

Keywords

3,4,5-Trimethoxyphenyl; Anticancer agents; Cytotoxic activity; Thiazole-2(3H)-thione; Tubulin polymerization.

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