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

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 kNN-MFA approach 30 3D-QSAR models were generated; one of these models was selected on the basis of q(2) and pred_r(2) values. The selected model has training set of 33 molecules and test set of 8 molecules with validation (q(2)) and cross validation (pred_r(2)) 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 A 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.