Журнал фармакогнозии и натуральных продуктов

Computer-aided drug design and analysis of some isonicotinic hydrazide-derived analogues against Mycobacterium Tuberculosis targets (3igo.pdb and 4duh.pdb)

Abstract

Naruka. S.Y

Isonicotinic acid hydrazide (INH) is the most important drug in the therapy of tuberculosis but not without some serious side effects. Therefore, with the use of computer aided drug design, the free amino group (-NH₂) present in INH was condensed with various carbonyl compounds to form hydrazones-Schiff bases. These hydrazones were further converted into thiazolidinones by the addition of thiaglycolic acid. As shown in Fig. 1 and 2, molecular docking studies of the designed compounds reveal that all the analogues possess better binding affinity (INH-140: -6.4Kcal/mol, INH-360: -6.5Kcal/mol,) compared to parent compound-INH (INH-78: -5.1Kcal/mol) at the target proteins (3igo.pdb and 4duh.pdb). INH exhibited a better PA (prediction activity) score compared to the designed analogues but all the analogues show less toxicity potential relatively.