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X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity
Version 1
: Received: 22 May 2024 / Approved: 22 May 2024 / Online: 23 May 2024 (10:01:34 CEST)
How to cite:
Teneva, Y.; Simeonova, R.; Besarboliev, O.; Sbirkova-Dimitrova, H.; Angelova, V. T. X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity. Preprints2024, 2024051470. https://doi.org/10.20944/preprints202405.1470.v1
Teneva, Y.; Simeonova, R.; Besarboliev, O.; Sbirkova-Dimitrova, H.; Angelova, V. T. X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity. Preprints 2024, 2024051470. https://doi.org/10.20944/preprints202405.1470.v1
Teneva, Y.; Simeonova, R.; Besarboliev, O.; Sbirkova-Dimitrova, H.; Angelova, V. T. X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity. Preprints2024, 2024051470. https://doi.org/10.20944/preprints202405.1470.v1
APA Style
Teneva, Y., Simeonova, R., Besarboliev, O., Sbirkova-Dimitrova, H., & Angelova, V. T. (2024). X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity. Preprints. https://doi.org/10.20944/preprints202405.1470.v1
Chicago/Turabian Style
Teneva, Y., Hristina Sbirkova-Dimitrova and Violina T. Angelova. 2024 "X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity" Preprints. https://doi.org/10.20944/preprints202405.1470.v1
Abstract
Taking into consideration the arising resistance towards the currently available antimycobacterial, there is still an unmet need for the development of new chemotherapeutic agents to combat the infectious agent. This study presents the X-ray single-crystal analysis to verify the structure of leading sulfonyl hydrazone 3b, which have proven their potent antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC value of 0.0716 μM, respectively, low cytotoxicity and very high selectivity indexes (SI=2216) and fully characterized by NMR and HRMS methods. Furthermore, this study assessed the ex vivo antioxidant activity, acute and subacute toxicity, and in vitro inhibition capacity against enoyl-ACP reductase of hydrazones 3a and 3b, as 3a was identified as the second leading compound in our previous research. Compared to isoniazid, compounds 3a and 3b demonstrated lower acute toxicity for intraperitoneal administration, with LD50 values of 866 and 1224.7 mg/kg, respectively. Subacute toxicity tests, involving the repeated administration of a single dose of the test samples per day, revealed no significant deviations in hematological and biochemical parameters or pathomorphological tissues. The compounds exhibited potent antioxidant capabilities, reducing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH). Enzyme inhibition assays of the sulfonyl hydrazones 3a and 3b with IC50 values of 18.2 µM and 10.7 µM, respectively and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. In conclusion, the investigated sulfonyl hydrazones display promising antitubercular drug-like properties and warrant further investigation.
Chemistry and Materials Science, Organic Chemistry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
