Isonicotinic Acid Hydrazide Derivatives: Synthesis, Antimycobacterial, Antiviral, Antimicrobial Activity and QSAR Studies

Vikramjeet      Judge; Balasubramanian      Narasimhan; Munish      Ahuja; Dharmarajan      Sriram; Perumal      Yogeeswar

Abstract

A series of isonicotinic acid hydrazide derivatives (1-14) was synthesized and tested for their in vitro antimycobacterial activity against Mycobacterium tuberculosis and the compounds with bromo, N2-2,4-hexadienoyl, N2-lauryl and N2-octadecanoyl groups were found to be the most effective, especially isonicotinic acid-N'-octadecanoyl hydrazide (12) was more active than the standard drug isoniazid. The results of antiviral activity testing showed that none of the tested compounds were active at subtoxic concentrations. The synthesized compounds were also screened for their antimicrobial potential against S. aureus, B. subtilis, E. coli, C. albicans and A. niger and the results indicated that compounds 4, 11, 12 and 14 were found to be active with Benzoic acid N'-(4-hydroxy-3,5-dimethoxy-benzylidene)-N-(pyridine-4- carbonyl)-hydrazide (14) having highest antimicrobial potential. The QSAR studies indicated the importance of topological parameters 3χ and κ1 in governing the antimicrobial activity of synthesized derivatives.

Keywords: Acylated isoniazid derivatives, Antimycobacterial, Antiviral, Antimicrobial, QSAR, Tuberculosis, Mycobacterium tuberculosis, ontubercular mycobacterial infections, human immunodeficiency virus (HIV), capreomycin, multi-antibiotic-resistant (MAR), mammalian proteins, Acquired immunodeficiency syndrome (AIDS), viral RNA, mRNA