Synthesis, Antiphospholipase A₂, Antiprotease, Antibacterial Evaluation and Molecular Docking Analysis of Certain Novel Hydrazones

El-Sayed NN 1 , Alafeefy AM 2 , Bakht MA 3 , Masand VH 4 , Aldalbahi A 5 , Chen N 6 Show all authors , Fan C 7 , Ben Bacha A 8

Affiliations 

  • 1 Department of Chemistry, College of Science, "Girls Section", King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia. [email protected]
  • 2 Department of Chemistry, Kulliyyah of Science, International Islamic University, P.O. Box 141, 25710 Kuantan, Malaysia. [email protected]
  • 3 Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia. [email protected]
  • 4 Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India. [email protected]
  • 5 Chemistry Department, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. [email protected]
  • 6 Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. [email protected]
  • 7 Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. [email protected]
  • 8 Biochemistry Department, Science College, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia. [email protected]
Molecules, 2016 Dec 02;21(12).
PMID: 27918459

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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