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

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

Ramar Sivaramakarthikeyan  1 , Shunmugam Iniyaval  1 , Vadivel Saravanan  1 , Wei-Meng Lim  2 , Chun-Wai Mai  2   3 , Chennan Ramalingan  1
Affiliations

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

Ramar Sivaramakarthikeyan et al. ACS Omega. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Anticancer drugs possessing benzimidazole structural motif.
Figure 2
Figure 2
Anticancer drugs possessing pyrazole scaffold.
Figure 3
Figure 3
General structure of target molecules.
Scheme 1
Scheme 1. Synthesis of Benzimidazole-Tethered Pyrazoles, 6a–6j
Scheme 2
Scheme 2. Plausible Mechanism
Figure 4
Figure 4
Two- and three-dimensional interactions of BCL-2 with 6h.
See this image and copyright information in PMC

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