Browsing by Author "Deekshit, V.K."

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Design, synthesis, characterization, and biological evaluation of novel pyrazine-1,3,4-oxadiazole/[1,2,4] triazolo[3,4-b][1,3,4]thiadiazine hybrids as potent antimycobacterial agents
(Elsevier B.V., 2024) Naik, S.; Dinesha, P.; Udayakumar, U.; Shetty, V.P.; Deekshit, V.K.
In this study, we present novel pyrazine-1,3,4-oxadiazole hybrids (T1-T9) and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (T10-T18), which possess remarkable antimicrobial activity. These compounds have been meticulously scrutinized for their efficacy in combatting the M. tuberculosis H37Rv strain. Three compounds T7, T8, and T17 showed promising antitubercular activity with MIC of 1.56 µg/mL. The target compounds are also evaluated for their antibacterial activity against S. aureus, S. mutans, E. coli, and S. Typhi, and antifungal activity against A. niger. Most of the compounds showed significant antibacterial and antifungal activity. All the active compounds exhibited very low toxicity and none of the active compounds were toxic to the normal cells. To deepen our understanding of these compounds, an in-silico ADME, and molecular docking analysis against the DprE1 enzyme were conducted, followed by DFT studies to shed some light on their electronic properties, and enhance our grasp of their pharmacological potential. © 2024 Elsevier B.V.
Synthesis and biological evaluation of novel hybrid compounds bearing pyrazine and 1,2,4-triazole analogues as potent antitubercular agents
(Royal Society of Chemistry, 2024) Naik, S.; Puttachari, D.; Vanishree, A.L.; Udayakumar, U.; Shetty, V.P.; Prabhu, C.; Deekshit, V.K.
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. © 2024 RSC.
Synthesis and in vitro Screening of Pyrazine-2-Carbohydrazide Derivatives as Potential Antimicrobial Agents
(World Scientific, 2024) Naik, S.; Dinesha, P.; Udayakumar, U.; Shetty, V.P.; Prabhu, C.; Deekshit, V.K.
Herein, we report the design of a new set of pyrazine-2-carbohydrazide derivatives (T1-T20) and in silico investigations to evaluate their inhibition activity against the enzyme, decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1). The derivatives interact with the Cys387 residue of the enzyme's active site through hydrogen bonds. Further, we synthesized these compounds and evaluated their efficacy against the M. tuberculosis H37Rv strain. Compounds T16 and T19 displayed promising antitubercular activity, boasting a minimal inhibitory concentration of 1.56 μg/mL. Furthermore, we assessed the antibacterial activity of these compounds against a range of pathogens, including S. aureus, S. mutans, E. coli and S.Typhi. Additionally, we evaluated their antifungal potency against A. niger. Notably, compounds T4, T8, T9, T16 and T19 exhibited noteworthy antibacterial activity against tested bacterial strains. Compounds T4, T9, T16, T17, T18 and T19 showed significant inhibition activity against A. niger. Importantly, all active compounds demonstrated low cytotoxicity, with IC50 values exceeding 300 μM, ensuring no harm to normal cells. To gain a deeper understanding of these compounds, we conducted in silico investigations to evaluate their pharmacokinetics and pharmacochemical properties. Additionally, we employed DFT studies to explore the electronic characteristics of these compounds, providing valuable insights into their potential applications in the pharmaceutical field. © 2024 World Scientific Publishing Company.