Document Type : Research Article
Authors
1
Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2
Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
3
Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
4
Tehran University of Medical Sciences, Tehran, Iran
5
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
According to the rising statistics of cancer cases, the discovery of novel anticancer drugs is a critical issue in current medical research. Besides, drug resistance and the incidence of severe adverse effects are the logical reasons for the discovery of new antineoplastic agents. According to the positive background that has been observed for 1,3-thiazole derivatives as potential anticancer drugs, we decided to synthesize a new series of 1,3-thiazole-based cytotoxic agents. MTT assay, activation of caspase 3, capability for reduction of the mitochondrial membrane potential (MMP), and production potency of reactive oxygen species (ROS) were investigated. Some of the tested compounds demonstrated potent cytotoxic activity and also caspase 3 activation, MMP reduction, and ROS generation. Three cancerous cell lines namely Hela (cervical cancer), A549 (lung carcinoma), and U87 (glioblastoma) were applied to perform the MTT assay. Diverse moieties with different electronic features were substituted on the phenyl ring to reveal the structure-activity relationships of the target compounds 8a-8o. Hela (cervical cancer), A549 (lung carcinoma), and U87 (glioblastoma) were utilized as cancerous cells to explore the cytotoxicity via MTT assay. Hela and U87 cells were more sensitive to the tested compounds and A549 was more resistant to the tested derivatives. Compound 8a with ortho chlorine moiety on the phenyl ring was the most active derivative against Hela cells (IC50 = 1.3±0.14 µM). All evaluated derivatives rendered lower activity against A549 than doxorubicin as a standard anticancer drug. Only some of the evaluated compounds showed more cytotoxicity against U87 than doxorubicin. Furthermore, caspase 3 activation, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation were also investigated. Fortunately, some of the tested compounds were also active in these tests. In conclusion, the current 1,3-thiazole derivatives could be suggested as potential anticancer lead compounds.
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