Biological approach of anticancer activity of new benzimidazole derivatives

Abstract

Compound 8 is the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/normoxia cytotoxic coefficient of compound 8 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - reference substance in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). The screening test of the caspase-dependent apoptosis proved that the exposure of compounds 1-2 and 7-8 against A549 cells for a 48 h promote apoptotic cell death. Additionally, the test of the DNA damage established that compounds 1, 2, 7, 8 are specific agents for the hypoxia-selective cytotoxicity of nitrobenzimidazoles [6,26].

Some characteristics of activity of potential chemotherapeutics – benzimidazole derivatives

“…a Reaction numbers: 1 -one electron reduction generates a prodrug radical; 2 -fragmentation of prodrug radical generates radical R and cytotoxin D; 3 -one electron reduction of the prodrug radical; 4 and 5 -subsequent reduction of the two electron reduction produces X; 6 -two-electron reduction of the prodrug generates product X. b CYPOR-NADPH -cytochrome P450 reductase, iNOS-inducible nitric oxide synthase, NQO-NAD(P)H dehydrogenase [quinone], CYP-cytochrome P 450. c Active cytotoxins (R, X, Y, Z). and benzimidazole-4,7-dione derivatives as we described earlier [15,16].…”

“…All these biochemical methods are thought to have been made in the same way as previously described procedures [15,16,19,20].…”

“…topoisomerase I or II, inhibitors of the VEGFR-2 and TIE-2 kinase receptors and inhibitors of the DNA repair enzyme poly(ADPribose) polymerase [8][9][10][11][12][13]. In this context, our experiments play an important role in application benzimidazole derivatives as a new potential cytotoxic agents [14][15][16][17][18]. The aim of the authors' study is to search for the new potential cytotoxic substances.…”

A series of 1,3-imidazoles and triazole-3-thiones based thiophene-2-carboxamides as anticancer agents: Synthesis and anticancer activity

“…In the last few decades, the chemistry of 1,2,4triazole-3-thiones, 1,3,4-thiadiazoles and their fused heterocyclic derivatives has received considerable attention owing to their effective biological activities as anticonvulsant [1,2] and antioxidant [3]. Several imidazole derivatives have been published as antiviral [4], anticoagulant [5] and anticancer [6,7] agents. The 1,2,4-triazole rings have been incorporated into a wide variety of therapeutically interesting drug candidates including antiviral (Ribavarin), antimigraine (Rizatriptan) ( Figure 1) [8][9][10], CNS stimulants sedatives and antianxiety [11,12] agents.…”

“…Synthesis of thiadiazine derivative (6) was achieved via reaction of compound 5 and maleic anhydride in triethyl amine. Heating of compound 5 with ethyl chloroacetate or sodium ethoxide produced thiadiazine derivative (7) and triazolethione (8), respectively. Thiosemicarbazide derivative 11 was synthesized by addition of nicotinic hydrazide to compound 1.…”