Synthesis, Antiphospholipase A2, Antiprotease, Antibacterial Evaluation and Molecular Docking Analysis of Certain Novel Hydrazones
Nahed N. E. El-Sayed,
Ahmed M. Alafeefy,
Mohammed A. Bakht,
Vijay H. Masand,
Ali Aldalbahi,
Nan Chen,
Chunhai Fan,
Abir Ben Bacha
Affiliations
Nahed N. E. El-Sayed
Department of Chemistry, College of Science, “Girls Section”, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
Ahmed M. Alafeefy
Department of Chemistry, Kulliyyah of Science, International Islamic University, P.O. Box 141, 25710 Kuantan, Malaysia
Mohammed A. Bakht
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia
Vijay H. Masand
Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India
Ali Aldalbahi
Chemistry Department, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Nan Chen
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
Chunhai Fan
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
Abir Ben Bacha
Biochemistry Department, Science College, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
Some novel hydrazone derivatives 6a–o were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and 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 towards hGIIA isoform of sPLA2 rather than DrG-IB with compounds 6l and 6e being the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease from Bacillus sp. with compound 6l being the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds; 6a, 6m, and 6o against P. aeruginosa; 6a, 6b, 6d, 6f, 6l, 6m, 6n, and 6o against Serratia; 6k against S. mutans; and compounds 6a, 6d, 6e, 6m, and 6n against E. feacalis. The docking simulations of hydrazones 6a–o with GIIA sPLA2, proteinase K and hydrazones 6a–e with glutamine-fructose-6-phosphate transaminase were performed to obtain information regarding the mechanism of action.
