Synthesis and Anticancer Activity of Novel Benzimidazole and Benzothiazole Derivatives against HepG2 Liver Cancer Cells

Abstract

Most of cancer chemotherapeutics and chemopreventives exert their effects by triggering apoptotic cell death. In this study, novel benzimidazole and benzothiazole derivatives have been synthesized to investigate their effects on HepG2 liver cancer cell lines after initial screening study. A dose response curve was constructed and the most active derivatives were further studied for apoptotic analysis. Six active benzimidazole derivatives (8, 9, 10, 12, 13 and 14) significantly induced apoptosis compared to control group. Two compounds 10 and 12 induced apoptosis by arresting cells in G1 phase of cell cycle which is confirmed by increased expression level of p21. The activity of caspase-3 which is well known as one of the key executioners of apoptosis was determined in the presence and absence of the tested derivatives. Our results indicated that compounds 10 and 12 significantly increased caspase-3 activity compared to control group. Moreover, a docked pose of compounds 10 and 12 was obtained bound to caspase-3 active site using Molecular Operating Environment module. This study demonstrated that benzimidazole derivatives 10 and 12 provoke cytotoxicity and induced apoptosis in liver cancer cells HepG2.

Evaluation of some new synthesis benzothiazole and benzimidazole Derivatives as potential antimicrobial and anticancer agents

“…The compounds 29 and 30 exhibited no activity (Table 3). Interestingly, the current results are in agreement with previous studies, which showed that some synthesized derivatives of benzothiazole and benzimidazole possessed noticeable anticancer activity (Youssef et al, 2012;Xiang et al, 2012).…”

Skin Damages—Structure Activity Relationship of Benzimidazole Derivatives Bearing a 5-Membered Ring System

“…In vitro antiproliferative activity of benzimidazole and benzothiazole derivatives against human melanoma cells (SK-Mel 5) was evaluated. Since benzimidazoles are recognized as potential anticancer drugs [ 10 ], we have also decided to examine the antiproliferative activity on other human cancer cells, including human T-lymphocyte cells (CEM), human cervical carcinoma cells (HeLa) and human pancreatic carcinoma cells (Mia Paca-2). Compound concentrations required to inhibit cell proliferation by 50% (in µM) are reported in Table 5 .…”

“…They are often found in large percentage in biomolecules like enzyme, vitamins and natural products [ 6 ]; for these reasons heterocyclic compounds remain the challenging issue for the researchers for the development of novel drugs [ 7 ]. Moreover, five membered-rings fused with benzene moiety attracted the attention of medicinal chemists especially benzimidazoles due to their diverse biological activities including antitumor [ 8 , 9 , 10 , 11 , 12 ], antifungal [ 13 ], anthelmintics [ 14 ], anti-inflammatory [ 15 ], analgesics [ 16 ] and antiviral [ 17 ]. Compounds belonging to this class of heterocycles are considered privileged due to their broad spectrum pharmacological activities [ 18 ].…”

“…(1H-pyrrol-2-yl)-1H-benzimidazole(10) Yellow solid in yield 55%; m.p. > 250 • C. IR (KBr) cm −1 : 2733.42, 1606 25,.…”

Synthesis of Novel Benzopyrone Substituted Benzimidazole Analogues as Antibacterial Agents

“…A number of drug candidates used in different therapeutic areas contain the benzimidazole ring such as antihypertensives, proton pump inhibitors, anti histaminics, anti helmintics. Compounds bearing benzimidazole moiety are reported to possess a number of interesting biological activities such as anticancer [1][2][3][4] , anthelmintic [5][6][7] , antiallergic [8][9] , antitubercular [10][11][12] , antioxidant [13][14] , antihistaminic [15][16][17] and antimicrobial [18][19][20][21][22][23][24][25][26][27] etc. There is a growing interest in the medicinal potential of natural products such as glycosides, alkaloids, flavones, coumarins etc.…”