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. 2021 Mar 31;6(14):9731-9740.
doi: 10.1021/acsomega.1c00369. eCollection 2021 Apr 13.

Synthesis and Biological Evaluation of Novel Benzhydrylpiperazine-Coupled Nitrobenzenesulfonamide Hybrids

Vallabhaneni S Murthy  1 , Yasinalli Tamboli  1 , Vagolu Siva Krishna  2 , Dharmarajan Sriram  2 , Fang Xiong Zhang  3   4 , Gerald W Zamponi  3   4 , Vijayaparthasarathi Vijayakumar  1
Affiliations

Synthesis and Biological Evaluation of Novel Benzhydrylpiperazine-Coupled Nitrobenzenesulfonamide Hybrids

Vallabhaneni S Murthy et al. ACS Omega. .

Abstract

A series of novel benzhydryl piperazine-coupled nitrobenzenesulfonamide hybrids were synthesized with good to excellent yields. They were tested for in vitro inhibition of mycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, in vitro cytotoxicity MTT (RAW 264.7cells) assay, nutrient starvation (H37Rv strain), and ability to block Cav3.2 T-type calcium channels. Novel hybrids did not inhibit T-type calcium channels, whereas they showed excellent antituberculosis (TB) activity and low cytotoxicity with a selectivity index of >30. A direct impact of the amino acid linker was not observed. Studied hybrids exhibited good inhibition activities, and the 2,4-dinitrobenzenesulfonamide group emerged as a promising scaffold for further drug design by hybridization approaches for anti-TB therapy.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Hybridization approach.
Scheme 1
Scheme 1. Synthesis of 1-Benzhydryl-4-(arylsulfonyl)piperazine
Figure 2
Figure 2
Biological activities of the active compounds against M. tuberculosis in the nutrient starvation model. Bacterial count estimation (mean ± S.D., n = 3) for control and treated groups were conducted by using the MPN (most probable number) assay (p < 0.0001, two-way ANOVA using GraphPad Prism software.)
Figure 3
Figure 3
Proposed mechanism of oxidative stress by 2,4-dinitrobenzenesulfonamides.
Figure 4
Figure 4
Brief SAR of novel hybrids.
See this image and copyright information in PMC

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