Issue 2, 2024

Synthesis and biological evaluation of novel hybrid compounds bearing pyrazine and 1,2,4-triazole analogues as potent antitubercular agents

Abstract

In this study, we elucidate the conceptualization and synthesis of hybrid compounds (T1–T18) amalgamating pyrazine and 1,2,4-triazole scaffolds. A total of eighteen compounds were screened in vitro for their efficacy against the Mycobacterium tuberculosis H37Rv strain via the MABA assay. The results revealed that eight compounds (T4, T5, T6, T11, T14, T15, T16, and T18) manifested noteworthy activity against Mtb, with minimum inhibitory concentration (MIC) values of ≤21.25 μM. Furthermore, we also examined these compounds for their antibacterial and antifungal properties against various strains. Compounds T4, T9, T10, T16, and T18 displayed significant antibacterial activity, while compounds T12 and T14 demonstrated significant antifungal activity. Subsequently, the most potent compounds were evaluated for their potential cytotoxicity to the Vero cell line via the MTT assay, revealing IC50 values surpassing 375 μM, indicative of minimal cytotoxicity. Additionally, we conducted in silico studies on these target molecules to better understand their action mechanisms. The in silico investigations suggest that the target enzyme involved in the action of the compounds may be DprE1. However, further experimental validation is necessary to ascertain the target responsible for the whole cell activity. All the target compounds are docked within the active site of the DprE1 enzyme, demonstrating favorable binding interactions. Furthermore, we predicted the ADME properties, physicochemical characteristics, and drug-like qualities of the target compounds using in silico methods. We also performed DFT studies to examine their electronic properties. These findings collectively indicate that the active compounds hold substantial promise as prospective contenders for the development of novel antitubercular agents.

Graphical abstract: Synthesis and biological evaluation of novel hybrid compounds bearing pyrazine and 1,2,4-triazole analogues as potent antitubercular agents

Supplementary files

Article information

Article type
Paper
Submitted
27 Nov 2023
Accepted
11 Mar 2024
First published
13 Mar 2024
This article is Open Access
Creative Commons BY-NC license

RSC Pharm., 2024,1, 283-295

Synthesis and biological evaluation of novel hybrid compounds bearing pyrazine and 1,2,4-triazole analogues as potent antitubercular agents

S. Naik, D. Puttachari, V. A. L., U. D., V. P. Shetty, C. Prabhu and V. K. Deekshit, RSC Pharm., 2024, 1, 283 DOI: 10.1039/D3PM00054K

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