Faculty Publications
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Item 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.Item Structure-based drug design and characterization of novel pyrazine hydrazinylidene derivatives with a benzenesulfonate scaffold as noncovalent inhibitors of DprE1 tor tuberculosis treatment(Springer Nature, 2024) Naik, S.; Dinesha, P.; Udayakumar, D.In this study, we present a novel series of (E)-4-((2-(pyrazine-2-carbonyl) hydrazineylidene)methyl)phenyl benzenesulfonate (T1-T8) and 4-((E)-(((Z)-amino(pyrazin-2-yl)methylene)hydrazineylidene)methyl)phenyl benzenesulfonate (T9-T16) derivatives which exert their inhibitory effects on decaprenylphosphoryl-?-D-ribose 2'-epimerase (DprE1) through the formation of hydrogen bonds with the pivotal active site Cys387 residue. Their effectiveness against the M. tuberculosis H37Rv strain was examined and notably, three compounds (namely T4, T7, and T12) exhibited promising antitubercular activity, with a minimum inhibitory concentration (MIC) of 1.56 µg/mL. The target compounds were screened for their antibacterial activity against a range of bacterial strains, encompassing S. aureus, B. subtilis, S. mutans, E. coli, S. typhi, and K. pneumoniae. Additionally, their antifungal efficacy against A. fumigatus and A. niger also was scrutinized. Compounds T6 and T12 demonstrated significant antibacterial activity, while compound T6 exhibited substantial antifungal activity. Importantly, all of these active compounds demonstrated exceedingly low toxicity without any adverse effects on normal cells. To deepen our understanding of these compounds, we have undertaken an in silico analysis encompassing Absorption, Distribution, Metabolism, and Excretion (ADME) considerations. Furthermore, molecular docking analyses against the DprE1 enzyme was conducted and Density-Functional Theory (DFT) studies were employed to elucidate the electronic properties of the compounds, thereby enhancing our understanding of their pharmacological potential. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.Item Noncovalent inhibitors of DprE1 for tuberculosis treatment: design, synthesis, characterization, in vitro and in silico studies of 4-oxo-1,4-dihydroquinazolinylpyrazine-2-carboxamides(Taylor and Francis Ltd., 2025) Naik, S.; Dinesha, P.; Udayakumar, U.In this study, we present a novel series of 4-oxo-1,4-dihydroquinazolinylpyrazine-2-carboxamide derivatives, which exert their inhibitory effect on decaprenylphosphoryl-?-D-ribose 2’-epimerase (DprE1) via the establishment of non-covalent interactions with the pivotal Cys387 residue located within the enzyme’s active site. These compounds underwent scrutiny for their efficacy in combatting the Mycobacterium tuberculosis H37Rv strain, and compounds T8 and T13 exhibited promising antitubercular activity, boasting a minimal inhibitory concentration (MIC) of 7.99 and 8.27 µM respectively. Additionally, three compounds, T2, T3 and T12, showcased substantial antibacterial activity whereas compounds T12 and T13 exhibited pronounced antifungal efficacy. Remarkably, all active compounds demonstrated negligible cytotoxicity, and none posed harm to normal cells. To attain a more profound comprehension of the attributes of these compounds, we conducted in silico investigations to evaluate their Absorption, Distribution, Metabolism and Excretion properties. Additionally, molecular docking analyses were executed to elucidate their interactions with the DprE1 enzyme. Finally, Density Functional Theory studies were leveraged to explore the electronic characteristics of these compounds, thereby providing insights into their potential utility in the realm of pharmaceuticals. © 2024 Informa UK Limited, trading as Taylor & Francis Group.Item Synthesis, Computational, and Photophysical Probing Interactions of Novel Isatin-Incorporated Thiazolyl-Coumarins as Potent Antitubercular Agents(John Wiley and Sons Inc, 2025) Vinay, K.K.; Bodke, Y.D.; Naik, S.; Udayakumar, U.In this work, we reported the synthesis of a novel series of isatin-incorporated thiazolyl-coumarin derivatives 4(a–h) by a one-pot three-component reaction of substituted isatin, thiosemicarbazide, and 3-(2-bromoacetyl) coumarin. The structures of the coumarin-thiazole scaffolds were precisely established by their IR, NMR, and HRMS spectral data. The UV–Vis absorption study of target molecules was investigated in six different solvents. Geometrical optimization, molecular electrostatic potential regions, and quantum chemical parameters were assessed using density functional theory (DFT) to explore the electronic properties of thiazolyl-coumarin derivatives. The synthesized compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis; all derivatives exhibited excellent antitubercular efficacy with MIC ? 3.25 µg/mL; among them, 4c and 4f were the most potent with a MIC of 1.56 µg/mL. Furthermore, in silico molecular docking analyses against the enoyl-ACP reductase (InhA) enzyme were conducted; all target ligands demonstrated favorable binding interactions within the active site of the InhA enzyme. © 2025 Wiley-VCH GmbH.Item 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.Item 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.