Numerous Heterocyclic Compounds with an Isonicotinic Moiety have Been Studied for Their Synthesis, Antibacterial, Anticancer, Docking Simulation, and DFT Characteristics

In this elucidation, we focused on the synthesis of isonicotinic heterocyclic molecules through reaction of isonicotinic acid hydrazide with phthalic anhydride, which produced an excellent yield of the equivalent N-(1,3-dioxoisoindolin-2-yl)isonicotinamide (3), and isonicotinic acid hydrazide can react easily with different aldehydes to form derivatives of Schiff bases. Furthermore, the reactivity of hydrazide with CS₂ which cyclized in the presence of acid to give the corresponding 1,3,4-oxadiazole in derivative 7, and the presence of NH₂NH₂ produced a 1H-1,2,4-triazole derivative 9 that readily reacted with phenacyl bromide with the elimination of -HBr to produce 6-phenyl-3-(pyridine-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (11). Hydrazide 1 reacts readily with many methylene compounds to produce a wide range of heterocycles. The presence of each produced heterocyclic was confirmed by spectral analysis investigation. Moreover, the synthesized compounds exhibited antimicrobial and antitumor activity against HepG2 liver tumor cells and neck squamous cell carcinoma (HNSCC) cancer cells, and the result was confirmed with different proteins through molecular docking simulation. Moreover, the optimization of the nicotinic compounds with DFT/B3LYP-631(G) basis set and determination of their physical descriptors correlated for its biological evaluation.