Design, Synthesis and Biological Evaluation of 1,3,4-Oxadiazole derivatives

Abstract

An alarming increase in bacterial strains resistant to existing antimicrobial agents, demands a renewed effort to seek agents effective against pathogenic bacterias resistant to current antimicrobials. In this paper we report 3D QSAR analysis for the 21 molecules of 1,3,4- oxadiazoles by using k-Nearest Neighbor Molecular Field Analysis (kNN-MFA) combined with various selection procedures. Using kNNMFA approach 30 3D-QSAR models were generated; one of these models was selected on the basis of q² and pred_r² values. The selected model has training set of 33 molecules and test set of 8 molecules with validation (q²) and cross validation (pred_r²) values of 0.6969 and 0.6148, respectively. The predicted activities by the developed models were in good accordance with the observed activities. In the present work, 1,3,4-oxadiazole derivatives (5a-e) were synthesized by the ring closure reactions of various acylhydrazides (4a-e) with carbon disulphide or with aromatic acids in POCl₃. The structures of all the compounds were elucidated by the spectral and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activity against E. coli, S. aureus and S. epidermidis.