Browsing by Author "Puttachari, D."

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    Imidazo[1,2-a]pyrimidine-Linked Pyridine, Pyrazine, and Pyrimidine Derivatives: Design, Synthesis, and Antitubercular Activity Evaluation
    (John Wiley and Sons Inc, 2025) Puttachari, D.; Naik, S.; Veeranagaiah, N.S.; Udayakumar, U.
    In this study, a molecular hybridization strategy was used to design a series of imidazo[1,2-a]pyrimidine-linked pyridine, pyrazine, and pyrimidine derivatives (T1–T20) and the hybrid compounds were synthesized via a multistep procedure. The structure of one of the target compounds T11, was studied using single-crystal X-ray diffraction investigation. These final molecules were thoroughly tested against Mycobacterium tuberculosis H37Rv strain, and compound T11 showed the best activity with MIC of 0.8 µg/mL, while compounds T5 and T18 showed promising inhibition activity (MIC 3.12 µg/mL). The target compounds were further tested for antibacterial activity against Staphylococcus aureus and Escherichia coli, finding the MIC and MBC values. Many of the compounds exhibited notable antibacterial properties. The promising anti-TB drugs (T5, T11, and T18) were shown to be nontoxic in toxicity studies on VERO cell lines. The combined results from in silico ADME, molecular docking, and DFT studies indicate that the active compounds possess strong potential as antitubercular candidates. © 2025 Wiley-VCH GmbH.
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    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.