Faculty Publications

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Subject: search.filters.subject.Antitubercular agents

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    Synthesis, computational and UV–Vis absorption studies of novel sulfathiazole azo sulfonamides acting as potent antitubercular agents
    (Elsevier B.V., 2025) K?k?, V.; Bodke, Y.D.; Naik, S.; Udayakumar, U.; O?, N.; Krishnamurthy, C.
    In this work, we have reported the synthesis of unprecedented sulfonamide azo dyes 4(a-j) by the diazo-coupling reaction of sulfathiazole with various coupling components. Different spectroscopic techniques, like FT-IR, NMR (1H and 13C), and HRMS, were used to precisely assess the structures of the target molecules. The UV–Vis absorption study was conducted using variety of organic solvents. Quantum chemical calculations, geometrical optimization, and molecular electrostatic potential regions of all sulfathiazole azo colorants were explored using (DFT)/B3LYP method. The efficacy of the synthesized dyes in combatting M. tuberculosis was examined using the MABA assay; the derivatives 4c and 4h demonstrated promising activity with MIC of 1.56 µg/mL. Further, in silico molecular docking study was performed to elucidate the interactions with enoyl-ACP reductase. Target compounds were screened for their antimicrobial activity using the broth microdilution method against two gram-positive, two gram-negative bacterial strains, and a fungal strain. The cytotoxic potential of the active compounds was assessed using the MTT assay against the Vero cell line. © 2024 Elsevier B.V.
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    Ionic liquid promoted facile one-pot synthesis of phenothiazine-thiazolidin-4-ones as potent antitubercular agents via mycobacterial ATP synthase inhibition
    (Elsevier B.V., 2025) Reddyrajula, R.; Etikyala, U.; Mahapathra, H.C.; Udaybhan, R.A.; Vijjulatha, V.; Udayakumar, U.
    The mycobacterial ATP synthase is responsible for the optimal growth, metabolism and viability of mycobacteria, establishing it as a validated target for the development of anti-TB therapeutics. Herein, we report the facile and efficient one-pot three component synthesis of 2-(10H-phenothiazin-3-yl)-3-substituted thiazolidin-4-one derivatives by using ionic liquid, 1?butyl?3-methylimidazolium bromide [Bmim]Br and their inhibitory potency against mycobacterium tuberculosis H37Rv strain (ATCC-27,294). Compound T27 exhibited the highest inhibition activity with an MIC of 0.78 ?g/mL, which is twofold and fourfold superior (in terms of the MIC values) to the standard first-line TB drugs isoniazid (MIC: 1.56 ?g/mL) and pyrazinamide (MIC: 3.12 ?g/mL) respectively. Two other compounds (T25 and T30) are equipotent as the isoniazid. The SAR studies revealed that insertion of 1,2,3-traizole and thiozolidine-2-one rings enhance the anti-TB activity in most of the tested compounds. Also, compound T27 was screened for mycobacterial ATP synthase inhibition activity and it exhibited an IC50 of 0.735 µM in M. smegmatis IMVs. Further, toxicity evaluation against VERO cell lines confirmed null cytotoxicity (selectivity index > 70) of the potent analogues. The title compounds are highly specific towards to the M. tb strain, i.e., most of the compounds exhibited moderate inhibitory potency against the tested bacterial strains (MIC ? 6.25 ?g/mL). In addition, molecular docking was employed against the active site of the ATP synthase enzyme to validate the binding mechanism and in vitro activity profile of the phenothiazine derivatives. Furthermore, in silico ADME and pharmacokinetic parameters’ prediction indicated good oral bioavailability. © 2024 Elsevier B.V.
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    Click chemistry assisted synthesis of imidazo[1,2-a]pyrimidine-1,2,3-triazole hybrids as promising antitubercular agents: Design, characterization, in-vitro biological evaluation, molecular docking, DFT and in-silico ADME studies
    (Elsevier B.V., 2025) P, D.; Naik, S.; Veeranagaiah, N.S.; Udayakumar, U.
    In this work, the molecular hybridization approach was employed to design a series of imidazo[1,2-a]pyrimidine -1,2,3-triazole derivatives (P1-P18), and the designed hybrid molecules were synthesized using a click chemistry protocol. The structure of one of the final compounds P10, was validated by single-crystal X-ray diffraction investigation. Among these 18 compounds, P3, P13, and P15 demonstrated encouraging antitubercular action against the M. tuberculosis H37Rv strain with minimum inhibitory concentrations (MIC) of 12.05 and 11.95 µM of (P3 and P13) or 6.75 µM (P15). In addition, at various concentrations, the target compounds demonstrated strong antifungal activity against P. anomala and A. flavus and antibacterial activity against S. aureus and Escherichia coli. The potent anti-TB agents (P3, P13, and P15) are non-toxic in the toxicity test performed using VERO cell lines. Furthermore, In-silico ADME, molecular docking (with InhA and CYP121), and DFT analysis data revealed that the active compounds have substantial potential as candidates for the development of novel antitubercular medicines. © 2025 Elsevier B.V.