Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

Ramar Sivaramakarthikeyan; Shunmugam Iniyaval; Vadivel Saravanan; Wei-Meng Lim; Chun-Wai Mai; Chennan Ramalingan

doi:10.1021/acsomega.0c00630

Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

ACS Omega. 2020 Apr 24;5(17):10089-10098. doi: 10.1021/acsomega.0c00630. eCollection 2020 May 5.

Authors

Ramar Sivaramakarthikeyan¹, Shunmugam Iniyaval¹, Vadivel Saravanan¹, Wei-Meng Lim², Chun-Wai Mai^{2

3}, Chennan Ramalingan¹

Affiliations

¹ Department of Chemistry, School of Advanced Sciences, Kalasalingam Academy of Research and Education (Deemed to be University), Krishnankoil 626 126, Tamilnadu, India.
² School of Pharmacy, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
³ Center for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia.

Abstract

Synthesis of a series of benzimidazole-ornamented pyrazoles, 6a-6j has been obtained from arylhydrazine and aralkyl ketones via a multistep synthetic strategy. Among them, a hybrid-possessing para-nitrophenyl moiety connected to a pyrazole scaffold (6a) exerted the highest anti-inflammatory activity, which is superior to the standard, diclofenac sodium. While executing the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, a hybrid-possessing para-bromophenyl unit integrated at the pyrazole structural motif (6i) exhibited the highest activity among the hybrids examined. Besides, evaluation of anticancer potency of the synthesized hybrids revealed that the one containing a para-fluorophenyl unit tethered at the pyrazole nucleus (6h) showed the highest activity against both the pancreatic cancer cells (SW1990 and AsPCl) investigated. Considerable binding affinity between B-cell lymphoma and the hybrid, 6h has been reflected while performing molecular docking studies (-8.65 kcal/mol). The outcomes of the investigation expose that these hybrids could be used as effective intermediates to construct more potent biological agents.