Synthesis and studying the antitumor activity of novel 5-(2-methylbenzimidazol-5-yl)-1,3,4-oxadiazole-2(3H)-thiones

The influence of the incorporation of 1,3,4-oxadiazole ring into 2-methyl-1H-benzimidazole derivatives producing a series of substituted 5(6)-(2-methylbenzimidazol-5-yl)-1,3,4-oxadiazoles on the antitumor activity was studied in this study. The antitumor activity of the new compounds was tested against breast cancer cell line MCF-7 and lung cancer cell line A549. S-5-(2-methyl-1H-benzo[d]imidazol-5-yl)-1,3,4-oxadiazol-2-yl 2-nitrobenzenesulfonothioate (9) showed potent activity against both MCF-7 and A549 cell lines. Whereas, compounds 7, 11-13 and 15-17 have moderate growth inhibitory activity on the two cell lines

Different synthetic routes to 4-(1H-benzo[d]imidazol-2-yl)aniline

The benzimidazole nucleus is an important pharmacophore in drug discovery, being a good bioisostere of naturally occurring nucleotides. This heterocycle may represent a type of privileged substructure which can interact with proteins and enzymes; it has, hence, been extensively utilized as a drug scaffold in medicinal chemistry. The connection between wide ranging biological activity and compounds containing the benzimidazole nucleus is known, and well documented in the literature. Benzimidazole derivatives have a multitude of interesting pharmacological activity, including antiviral, antitumor, antihypertensive, proton pump inhibitory, anthelmintic, antimicrobial, and anti-inflammatory activity. Accordingly, a brief survey is given below covering the synthesis of 2- phenybenzimidazole derivatives and their biological importance

Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles

In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is two-fold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in comparison to sorafenib (% inhibition = 92%). Studying the effect of 17a on the HepG2 cell cycle demonstrated that 17a arrested the cell cycle at the G2/M phase and induced a dose-dependent apoptotic effect. Molecular docking studies of the synthesized 1,2-disubstituted benzimidazoles in the VEGFR-2 active site displayed their ability to accomplish the essential hydrogen bonding and hydrophobic interactions for optimum inhibitory activity

Synthesis, <i>in vitro</i> and <i>in vivo</i> antitumor and antiviral activity of novel 1-substituted benzimidazole derivatives

<div><p></p><p>A novel series of 5-nitro-1<i>H</i>-benzimidazole derivatives substituted at position 1 by heterocyclic rings was synthesized. Cytotoxicity and antiviral activity of the new compounds were tested. Compound <b>3</b> was more active than doxorubicin against A-549, HCT-116 and MCF-7. However, compound <b>3</b> showed no activity against human liver carcinoma Hep G-2 cell line. Compounds <b>9</b> and <b>17b</b> (<i>E</i>) showed potency near to doxorubicin against the four cell lines. The acute toxicity of compound <b>9</b> on liver cancer induced in rats was determined <i>in vivo</i>. Interestingly, it showed restoration activity of liver function and pathology towards normal as compared to the cancer-bearing rats induced by DENA. Compounds <b>17a</b> (<i>Z</i>), <b>17b</b> (<i>E</i>) and <b>18a</b> (<i>Z</i>) were the most promising compounds for their antiviral activity against rotavirus Wa strain.</p></div