One pot facile synthesis of flavanoidal oxadiazinanones: In vitro antibacterial activity, docking and MD simulation using DNA gyrase

A series of novel flavanoidal oxadiazinanone derivatives namely 2-phenylspiro[chroman-4,2′-[1,3,4]oxadiazinan]-5′-one(6), 2-(2-hydroxyphenyl) spiro[chroman-4,2′-[1,3,4] oxadiazinan]-5′-one(7),2-(3-hydroxyphenyl)spiro[chroman-4,2′-[1,3,4oxadiazinan]-5′-one(8),2-(4‑hydroxy phenyl)spiro[chroman-4,2′- [1,3,4] oxadiazinan]-5′-one(9),7‑hydroxy-2-phenylspiro[chroman-4,2′-[1,3,4]oxadiazinan]-5′-one (10) have been synthesized with cyanoacetohydrazide by the reaction of flavanone and its derivatives employing facile reaction pathway. IR, ¹H NMR, ¹³C NMR and MS data were employed for structural assignment of synthesized compounds. The in vitro antibacterial activity of synthesized compounds (6–10) was conducted using the broth microdilution method against different gram-negative bacterial strains (AK-125, AK-68, AK-92 and AK-132). All synthesized compounds showed high antibacterial activity as compared with the standard antibiotics Cefotaxime, Cefoxitin, and Ceftazidime. Molecular docking studies of all synthesized compounds determine the bonding interaction with amino residues of DNA gyrase through hydrogen bonding. The molecular dynamic simulation study revealed that (6) and (9) had better binding, and (7) and (8) had been shown to be stably connected to DNA gyrase compared to standard antibiotic novobiocin. Scanning electron microscopy analysis manifested agglomeration pertaining to brick-shaped crystals of flavanoidal oxadiazinanone.