99303-41-0Relevant academic research and scientific papers
The design and synthesis of potent benzimidazole derivatives via scaffold hybridization and evaluating their antiproliferative and proapoptotic activity against breast and lung cancer cell lines
Elgawish, Mohamed Saleh,Ghareb, Nagat,Nafie, Mohamed S.,Yamada, Koji,Yassen, Asmaa S. A.
, p. 4239 - 4256 (2022/03/14)
One of the current approaches used in drug discovery and development is the synthesis of novel small compounds from existing structural motifs via molecular hybridization. In the current study, a new series of benzimidazo[1,5-a]imidazole, benzimidazo[1,2-c]thiazole, benzimidazotriazine, and benzimidazo[1,2-c]quinazoline scaffolds was synthesized via C-H cycloamination, using a metal-free synthetic pathway, as potent antiproliferative antiangiogenic molecules against breast (MCF-7) and lung (A549) cancer cell lines. The expansion of the benzimidazole scaffold with heterocyclic rings resulted in a tridentate cyclic system that occupied the ATP-binding site and neighboring hydrophobic pocket, eliciting promising affinity and selectivity toward VEGFR2 through extra H-bonding and completely occupying the entrance region. Molecular docking studies demonstrated that most of the designed compounds bind VEGFR-2 adopting a DFG-in conformation, where the benzimidazole scaffold occupied the hinge region, the central aromatic ring occupied hydrophobic region I adjacent to the hinge region, and the hydrogen bond donor/acceptor bound to the hydrogen-bond-rich region. In comparison to lenvatinib, which had a docking score of-12.47 kJ mol-1 and a Glide E-model value of-132.68 kcal mol-1, compound 17 had a decent docking score of-8.95 kJ mol-1 and a Glide E-model value of-92.17 kcal mol-1. The designed molecules exhibited promising in situ cytotoxic activities, with IC50 values ranging from 9.2 to 42.3 μM against MCF-7 and A549, comparable to 5-fluorouracil (which has IC50 values of 10.32 and 5.8 μM against MCF-7 and A549, respectively); they also showed selective in vitro inhibitory activity against VEGFR2 when compared with other designed kinases, with compound 17 showing an IC50 value (23 nM) as good as that of sorafenib (30 nM). Flow cytometry and cell cycle assays revealed that apoptotic cell death induction occurred in the A549 cell line through the activation of certain caspases and the tumor suppressor P53 and through repressing the generation of BAX and PUMA. Furthermore, the proposed compounds exhibited physicochemical and pharmacokinetics properties within the acceptable range for human usage, as anticipated by an in silico ADME study, making them lead molecules for developing new forms of medication.
Anti-cancer activity of two novel heterocyclic compounds through modulation of VEGFR and miR-122 in mice bearing Ehrlich ascites carcinoma
Hazem, Reem M.,Mohamed, Anhar A.,Ghareb, Nagat,Mehanna, Eman T.,Mesbah, Noha M.,Abo-Elmatty, Dina M.,Elgawish, Mohamed Saleh
, (2020/12/02)
Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). Breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5 mg/kg and 10 mg/kg), (6&7) benzimidazotriazin treated (5 mg/kg and 10 mg/kg). The expression of miR-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum ALT, AST, creatinine, and urea were measured. Treatment with benzoimidazoquinazoline and benzimidazotriazin decreased tumor weight and serum levels of VEGF, and down-regulated expression of VEGFR2 and CD34 in the tumor tissue. miR-122 was upregulated, particularly in the benzimidazotriazin (10 mg/kg) group. Relative to cisplatin, the novel compounds were less toxic to kidneys. Benzoimidazoquinazoline and benzimidazotriazin are promising anti-cancer agents that act through inhibition of angiogenesis and thus provide a new strategy for advancement of chemotherapy.
Synthesis and Pharmacological Investigations of Novel Pyrazolyl and Hydrazonoyl Cyanide Benzimidazole Entities
Khalifa, Mohamed E.,Gobouri, Adil A.,Kabli, Fahad M.,Altalhi, Tariq A.,Almalki, Abdulraheem S. A.,Elemshaty, Amira M.
, p. 1426 - 1436 (2019/04/17)
Various novel benzimidazole entities linked to pyrazolyl and hydrazonoyl cyanide substrates carrying aryl and heteroaryl groups (8a–e to 10a–e) were synthesized using new route syntheses and were focused on their pharmacological evaluation as one of the m
Synthesis, antitumor activity and SAR study of novel [1,2,4]triazino[4,5-a] benzimidazole derivatives
El-Nassan, Hala Bakr
experimental part, p. 22 - 27 (2012/07/27)
A series of novel 1,2,3,4-tetrahydro[1,2,4]triazino[4,5-a]benzimidazoles carrying variety of aryl and heteroaryl groups at position 1 were synthesized. The newly synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7). Some of the test compounds showed potent antitumor activity, especially compound 3c [1-(2-chlorophenyl) derivative] which displayed the highest activity among the test compounds.
LE 2-HYDROXYMETHYLBENZIMIDAZOLE PRECURSEUR DE SYNTHESE DE NOUVEAUX SYSTEMES HETEROCYCLIQUES
Essassi, E. M.,Fifani, J.,Hamamsi, I.
, p. 83 - 84 (2007/10/02)
The easy synthesis of 2-hydroxymethylbenzimidazole, leads us to use this compound in the preparation of new heterocyclic systems.
