Biological evaluation of the toxicity and the cell cycle interruption by some benzimidazole derivatives

Abstract

In this work, the in vitro tests of biological activity of benzimidazoles were conducted. This group of benzimidazole derivatives was evaluated as potential bioreductive agents and their characteristic pro-apoptosis activity and cell cycle interruption on the human lung adenocarcinoma A549 cells were discussed. Their toxicity on the healthy human erythrocytes and their influence on the healthy human erythrocytes acetylcholinesterase enzyme (AChE) were established. Their apoptosis activity on A549 cells line was determined by Annexin V-APC test, and it was visualized by Hoechst test. In the next stage, their influence on the cell cycle interruption was determined by using the ribonuclease reagent. The AChE inhibition test was defined by the Ellman method, and the red blood cell lysis was defined by erythrotoxicity test. The results proved the pro-apoptosis properties of all tested compounds in normoxia and hypoxia. The DNA content assay showed that the benzimidazoles possess the ability to interrupt S phase of tumor cell cycle. The best activity in this action was presented by compound 1, especially in hypoxia, and it proves that the N-oxide analogs are predispositioned to the hypoxic target. In this study, the benzimidazoles were found as potentially biocompatible and their inhibition of acetylcholinesterase was lower than tirapazamine and much lower than tacrine which constitutes their desired effect of potential biological activity.

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

“…Introduction of the hydrophobic substituent (-Cl, -Me, -CF 3 ) as well as -OMe on the heterocyclic ring or -Cl in the aryl moiety enhances biological activity of analogs in comparison to the unsubstituted bib-1,3-diol. The activity of compounds with the ethyl ester group is moderate (8)(9)(10) and it deteriorates with the addition of the hydroxyl substituent. On the other hand, taking into account the values of the calculated descriptors (Table 5), the low tPSA as well as MR favor the activity.…”

“…Free of amine group benzimidazole derivatives were also presented as AChE/BuChE inhibitors. They include 2-(chloro/nitro)arylbenzimidazoles [9] and N-substituted-2-aryl-1H-benzimidazole-5-carboxylates [10]. The highest activity against AChE was found for 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzimidazole-5-carboxylate (compound c, Figure 1) [10].…”

“…A prominent (nanomolar) activity against AChE/BuChE was found for the pyrazolobenzothiazine-benzimidazole hybrids (compound f, Figure 1) [13] and the benzimidazole-based organophosphorus compounds [14]. Most of the mentioned compounds are the multitargeted agents: carbonic anhydrase inhibitors [11], antioxidants [7], interrupters of cell cycle [9], Fe 2+ ion chelators [11]. Some of them show anticancer potency [9,15] or neuroprotective properties [8].…”

“…Most of the mentioned compounds are the multitargeted agents: carbonic anhydrase inhibitors [11], antioxidants [7], interrupters of cell cycle [9], Fe 2+ ion chelators [11]. Some of them show anticancer potency [9,15] or neuroprotective properties [8]. Benzimidazole derivatives are also known as β-glucuronidase [16,17], α-glucosidase [18,19], urease [20], and α-amylase enzymes inhibitors [21].…”

Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives

“…The evaluation of cytotoxic activity has been done by assessing the stage of cell death as early-and late-apoptotic or necrotic cells. 15,18,19 Results and discussion…”