Faculty Publications

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Author: search.filters.author.Udayakumar, D.Subject: search.filters.subject.controlled study

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    Ionic liquid-promoted one-pot synthesis of thiazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids and their antitubercular activity
    (Royal Society of Chemistry, 2016) Ramprasad, J.; Nayak, N.; Udayakumar, D.; Yogeeswari, P.; Sriram, D.
    In this paper, we report the facile and efficient one-pot three-component synthesis of 1-((6-phenylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)-2-(4-phenylthiazol-2-yl)hydrazine derivatives (5a-w) using an ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([Bmim]Br). The compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis. Compound 5s showed the highest inhibitory activity with an MIC of 6.03 ?M which is slightly lower than the MIC values of standard drugs ethambutol (15.3 ?M) and ciprofloxacin (9.4 ?M). Four other compounds of the series viz.5e, 5i, 5t and 5w also showed significant inhibitory activity with MIC values in the range of 11.7-13.9 ?M. The structure-activity relationship revealed that the trifluoromethyl substitution at position-2 and p-chlorophenyl substitution at position-6 of the imidazo[2,1-b][1,3,4]thiadiazole ring enhanced the inhibitory activity. Also, the methyl, methoxy, fluoro or nitro substituents on the thiazole ring enhanced the activity of the compounds. None of the active compounds were toxic to a normal cell line (NIH 3T3), which signifies the lack of general cellular toxicity of the molecules. In silico molecular docking studies revealed the favourable interaction of the potent compounds with the target enzymes InhA and CYP121. © The Royal Society of Chemistry 2016.
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    Novel Indole-Quinazolinone Based Amides as Cytotoxic Agents
    (HeteroCorporation support@jhetchem.com, 2016) Gokhale, N.; Panathur, N.; Udayakumar, D.; Nayak, P.G.; Pai, K.S.R.
    Indole-quinazolinone hybrids with active amides were synthesized, characterized, and assessed for their cytotoxicity. Two molecules displayed substantial activity in sulphorhodamine B assay method. © 2015 HeteroCorporation.
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    A novel and ultrasensitive high-surface porous carbon-based electrochemical biosensor for early detection of dengue virus
    (Elsevier Ltd, 2024) Hegde, S.S.; Naik, S.; Badekai Ramachandra, B.R.; Mishra, P.; Udayakumar, D.; Ahmed, M.U.; Santos, G.N.
    Dengue fever, a mosquito-borne viral infection, poses a significant global health threat, and early diagnosis is crucial for effective disease management. The utilization of advanced materials in the design ensures an improved surface area, facilitating a heightened interaction between the sensor and the target. In this study, the incorporation of biomass-derived high-surface porous carbon-based materials not only contributed to the sensor's sensitivity but also ensured a cost-effective and scalable manufacturing process. The electrochemical nature of the biosensor added a layer of precision to the detection process and offered a reliable, rapid method for identifying the infection of the dengue virus. The enhanced sensitivity of the biosensor allowed the detection of even trace amounts of the NS1 protein, enabling early diagnosis in the initial stages of dengue infection. The system exhibited a high sensitivity with a wide linear range between 1 pg/mL and 100 μg/mL, and the extremely low detection limit of 0.665 pg/mL ranks this as one of the most efficient biosensors for the detection of dengue virus NS1 protein. Selectivity studies, coupled with computational insights, showcased the biosensor's prowess in distinguishing NS1 protein from potential interfering substances, laying the foundation for reliable diagnostics in complex biological matrices. Real sample analysis using human serum spiked with NS1 protein offers a tantalizing glimpse into the transformative potential of biosensors in real-world scenarios. This innovative biosensor holds great promise for addressing the pressing need for early detection of dengue virus infections. © 2024 The Authors
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    N-Acyl phenothiazines as mycobacterial ATP synthase inhibitors: Rational design, synthesis and in vitro evaluation against drug sensitive, RR and MDR-TB
    (Academic Press Inc., 2024) Reddyrajula, R.; Perveen, S.; Negi, A.; Etikyala, U.; Vijjulatha, V.; Sharma, R.; Udayakumar, D.
    The mycobacterial F-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 discovery of an N-acyl phenothiazine derivative, termed PT6, targeting the mycobacterial F-ATP synthase. PT6 is bactericidal and active against the drug sensitive, Rifampicin-resistant as well as Multidrug-resistant tuberculosis strains. Compound PT6 showed noteworthy inhibition of F-ATP synthesis, exhibiting an IC50 of 0.788 µM in M. smegmatis IMVs and was observed that it could deplete intracellular ATP levels, exhibiting an IC50 of 30 µM. PT6 displayed a high selectivity towards mycobacterial ATP synthase compared to mitochondrial ATP synthase. Compound PT6 showed a minor synergistic effect in combination with Rifampicin and Isoniazid. PT6 demonstrated null cytotoxicity as confirmed by assessing its toxicity against VERO cell lines. Further, the binding mechanism and the activity profile of PT6 were validated by employing in silico techniques such as molecular docking, Prime MM/GBSA, DFT and ADMET analysis. These results suggest that PT6 presents an attractive lead for the discovery of a novel class of mycobacterial F-ATP synthase inhibitors. © 2024 Elsevier Inc.
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    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.