Yazar "Krishna, Vagolu Siva" seçeneğine göre listele

Listeleniyor 1 - 2 / 2
  • [ X ]
    Öğe
    Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2020) Dogan, Hilal; Dogan, Sengul Dilem; Gunduz, Miyase Gozde; Krishna, Vagolu Siva; Lherbet, Christian; Sriram, Dharmarajan; Sahin, Onur
    Tuberculosis, caused by Mycobacterium tuberculosis, is a serious infectious disease and remains a global health problem. There is an increasing need for the discovery of novel therapeutic agents for its treatment due to the emerging multi-drug resistance. Herein, we present the rational design and the synthesis of eighteen new thiadiazolylhidrazones (TDHs) which were synthesized by intramolecular oxidative N-S bond formation reaction of 2-benzylidene-N-(phenylcarbamothioyl)hydrazine-lcarboximidamide derivatives by phenyliodine(III) bis(trifluoroacetate) (PIFA) under mild conditions. The compounds were characterized by various spectral techniques including FTIR, H-1 NMR, C-13 NMR and HRMS. Furthermore, the proposed structure of TDH12 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Rv. Among them, some compounds exhibited remarkable antimycobacterial activity, MIC = 0.78-6.25 mu g/mL, with low cytotoxicity. Additionally, the most active compounds were screened for their biological activities against M. tuberculosis in the nutrient starvation model. Enzyme inhibition assays and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. (C) 2020 Elsevier Masson SAS. All rights reserved.
  • [ X ]
    Öğe
    Linking azoles to isoniazid via hydrazone bridge: Synthesis, crystal structure determination, antitubercular evaluation and computational studies
    (Elsevier, 2022) Aslan, Ebru Kocak; Krishna, Vagolu Siva; Armakovic, Sanja J.; Armakovic, Stevan; Sahin, Onur; Tonjum, Tone; Gunduz, Miyase Gozde
    The current emergence of drug-resistant and multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains has complicated and hampered attempts to eliminate or considerably reduce the global prevalence of the often life-threatening disease tuberculosis (TB). Hence, the development of novel antitubercular agents is crucial to combat this challenge. Here, we applied the molecular hybridization approach to link isoniazid (INH), the frontline antitubercular drug, to various azole rings (pyrazole, imidazole, and triazole) through hydrazone functionality. The designed compounds were synthesized and characterized by using spectral techniques including IR, H-1 NMR, C-13 NMR and HRMS. Additionally, single crystal X-ray analysis was employed to resolve the proposed chemical structure of INH-T. All compounds were then extensively screened for their antitubercular activities against Mtb H37Rv, drug-resistant and MDR Mtb strains, as well as against a clinical Mtb isolate with no mutation. Notably, INH-azole hybrids presented outstanding antimycobacterial activity with negligible cytotoxicity. Computational methods based on density functional theory calculations and molecular dynamics simulations were applied to identify the characteristic reactive centers of the title compounds, predict stability towards autoxidation, understand their interactions with water molecules and predict the temperature dependence of density. Finally, molecular docking studies revealed that new INH-azole hybrids are likely to exert their antimycobacterial activity via direct inhibition of the Mtb InhA enzyme. (C) 2022 Elsevier B.V. All rights reserved.