<i>N'</i>-Isonicotinoylnicotinohydrazonamide: Synthesis, Crystal Structure and Computational Studies
ASIAN JOURNAL OF ORGANIC CHEMISTRY, vol.15, no.1, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 15 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1002/ajoc.70292
- Journal Name: ASIAN JOURNAL OF ORGANIC CHEMISTRY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
- Azerbaijan State University of Economics (UNEC) Affiliated: No
Abstract
An Isoniazid derivative, N'-isonicotinoylnicotinohydrazonamide (1), was synthesized via a reaction between Isoniazid and 3-cyanopyridine. It was established that 1 adopts a keto conformation in the solid state, forming a 2D supramolecular network stabilized by N & horbar;H & ctdot;O and N & horbar;H & ctdot;N hydrogen bonds. The NMR studies indicated the presence of two conformational isomers, a behavior attributed to the greater flexibility imparted by the meta-positioned nitrogen in the nicotinoyl moiety, in contrast to its rigid picolinoyl-containing isomer 2, which was reported by us previously. Hirshfeld surface analysis quantified the intermolecular interactions of 1, identifying H & ctdot;H, H & ctdot;C, H & ctdot;N, and H & ctdot;O contacts as the most significant contributors to the crystal packing. DFT calculations provided insights into the electronic structure, molecular electrostatic potential, and global reactivity descriptors, which characterized 1 as a strong electrophile. A combined QTAIM/NCI analysis confirmed the presence of prominent intramolecular interactions. In silico ADMET profiling of 1 predicted a favorable pharmacokinetic profile with high gastrointestinal absorption but potential hepatotoxicity and neurotoxicity. Molecular docking studies against key Mycobacterium tuberculosis proteins, viz. Proteasomal ATPase Mpa, Serine/threonine-protein kinase, and Arabinosyltransferase, demonstrated that 1 exhibits superior binding affinity and ligand efficiency compared to the parent Isoniazid, suggesting its potential as a promising lead compound for anti-tuberculosis drug development.