title: Synthesis, Antiphospholipase A₂, Antiprotease, Antibacterial Evaluation and Molecular Docking Analysis of Certain Novel Hydrazones.
abstract: Some novel hydrazone derivatives6a-owere synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide5and characterized using IR, ¹H-NMR,13C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A₂ (sPLA₂), three protease enzymes and eleven bacterial strains were evaluated. The results revealed that all compounds showed preferential inhibition towardshGIIA isoform of sPLA₂ rather than DrG-IB with compounds6land6ebeing the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease fromBacillussp. with compound6lbeing the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds;6a,6m, and6oagainstP. aeruginosa;6a,6b,6d,6f,6l,6m,6n, and6oagainstSerratia;6kagainstS. mutans; and compounds6a,6d,6e,6m, and6nagainstE. feacalis.The docking simulations of hydrazones6a-owith GIIA sPLA₂, proteinase K and hydrazones6a-ewith glutamine-fructose-6-phosphate transaminase were performed to obtain information regarding the mechanism of action.
authors.affiliation: Department of Chemistry, College of Science, "Girls Section", King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia. nelsayed@ksu.edu.sa.|National Organization for Drug Control and Research, Giza 35521, Egypt. nelsayed@ksu.edu.sa.
authors.forename: Nahed N E
authors.initials: NN
authors.lastname: El-Sayed
authors.affiliation: Department of Chemistry, Kulliyyah of Science, International Islamic University, P.O. Box 141, 25710 Kuantan, Malaysia. ahmed.alafeefy@gmail.com.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Alafeefy
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia. bakhtpharm@gmail.com.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Bakht
authors.affiliation: Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India. vijaymasand@gmail.com.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Masand
authors.affiliation: Chemistry Department, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. aaldalbahi@ksu.edu.sa.
authors.forename: Ali
authors.initials: A
authors.lastname: Aldalbahi
authors.affiliation: Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. chennan@sinap.ac.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. fchh@sinap.ac.cn.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Fan
authors.affiliation: Biochemistry Department, Science College, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia. aalghanouchi@ksu.edu.sa.
authors.forename: Abir
authors.initials: A
authors.lastname: Ben Bacha
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001407:Bacillus / Q000254:growth & development; D001549:Benzamides / Q000737:chemistry; D019286:Endopeptidase K / Q000037:antagonists & inhibitors*; D013293:Enterococcus faecalis / Q000254:growth & development; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D064801:Phospholipase A2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D011550:Pseudomonas aeruginosa / Q000254:growth & development; D012705:Serratia / Q000254:growth & development; D013295:Streptococcus mutans / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001549:Benzamides; D006835:Hydrazones; D064801:Phospholipase A2 Inhibitors; D011480:Protease Inhibitors; C037689:benzamide; D019286:Endopeptidase K
keywords: N-acylhydrazones; antimicrobial evaluation; aroylhydrazides; benzo[d][1,3]oxazin-4-one; benzylidene hydrazides; hydrazones; molecular docking; phospholipases; proteases