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

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.