Synthesis of isoniazid derivatives and evaluation of their α-chymotrypsin inhibitory effect through in silico guided in vitro studies.

Autor: Shirazi SH; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Rizvi F; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Sherwani ZA; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Siddiqui AR; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Ul-Haq Z; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Siddiqui H; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Choudhary MI; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Ahmad MS; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. Electronic address: shoaib.hej@gmail.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 26; Vol. 735, pp. 150805. Date of Electronic Publication: 2024 Oct 11.
DOI: 10.1016/j.bbrc.2024.150805
Abstrakt: Alpha-chymotrypsin is a serine protease. Its overexpression is responsible for several ailments, such as chronic obstructive pulmonary disease, autoimmune diseases, pancreatitis, and colon cancers. Therefore, the discovery of potent α-chymotrypsin inhibitors is essential for the treatment of the aforementioned ailments. In this study, we identified new α-chymotrypsin inhibitors through a systematic approach, utilizing the in silico and in vivo studies to predict and confirm the inhibitory potential of isoniazid derivatives. During this study, six compounds 2, 3, 4, 7, 9, and 10 were shortlisted from ten isoniazid derivatives through in silico screening. After that, MD simulations were performed for these compounds. The shortlisted compounds were evaluated through an in vitro α-chymotrypsin inhibitory assay. Compounds 9 and 10 showed a potent inhibition against α-chymotrypsin. The identified compounds or their derivatives can be further investigated as drug leads against the ailments caused by α-chymotrypsin and related serine proteases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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