TY - JOUR
T1 - Synthesis, antiphospholipase A2, antiprotease, antibacterial evaluation and molecular docking analysis of certain novel hydrazones
AU - El-Sayed, Nahed N.E.
AU - Alafeefy, Ahmed M.
AU - Bakht, Mohammed A.
AU - Masand, Vijay H.
AU - Aldalbahi, Ali
AU - Chen, Nan
AU - Fan, Chunhai
AU - Bacha, Abir Ben
N1 - Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Antimicrobial evaluation
KW - Aroylhydrazides
KW - Benzo[d][1,3]oxazin-4-one
KW - Benzylidene hydrazides
KW - Hydrazones
KW - Molecular docking
KW - N-acylhydrazones
KW - Phospholipases
KW - Proteases
UR - http://www.scopus.com/inward/record.url?scp=85002998489&partnerID=8YFLogxK
U2 - 10.3390/molecules21121664
DO - 10.3390/molecules21121664
M3 - Article
C2 - 27918459
AN - SCOPUS:85002998489
SN - 1420-3049
VL - 21
JO - Molecules
JF - Molecules
IS - 12
M1 - 21121664
ER -