Synthesis, spectral studies and evaluation of 4-(5-substituted- [1,3,4] oxadiazol-2-ylmethoxy)-thieno[2,3-d]pyrimidines as novel antimicrobials

Since resistance of pathogenic bacteria towards available antibiotics has become a major worldwide problem, the design of new compounds to deal with resistant bacteria is one of the most important areas of antibacterial research today. As it is known about the wide spectrum biological activities of fused pyrimidine including antimicrobial activity, it has been thought worthwhile to synthesis thienopyrimidines. In search for new biodynamic potent molecule, it was thought useful to attach 1,3,4-oxadiazoles which are also lead molecules against microbes and in the present study 1,3,4-oxadiazole attached to thienopyrimidine nucleus. Various 4-(5-sustituted-[1,3,4]oxadiazol-2- ylmethoxy)-thieno[2,3-d]pyrimidines have been synthesized by means of reported methods and all the test compounds was assayed in vitro for antibacterial activity against two different Gram-negative (K. pneumoniae MTCC 39 and S. typhi CNCTC 786) and Gram-positive (S. aureus ATCC 3750, Bacillus subtilis MTCC 121) bacteria each and for antifungal activity against Candida albicans (MTCC 183). The MIC was determined by Rezasurin microplate method. The structure of 4-[(5-substituted-1,3,4-oxadiazol-2-yl)methoxy] thieno[2,3-d]pyrimidines (7a-7j) has been confirmed by spectral studies. Among the compounds tested for antimicrobial activity, four compounds 7(c, d, e, j) have shown potent activity against Gram-positive S. aureus with MIC value below 3.9 μg/ml. Compounds 7c and 7d have shown better activity towards Bacillus subtilis too. Compounds 7c and 7e have shown better activity against Candida albicans with the MIC values 125 μg/ml. The newly synthesized compounds are active against S. aureus specifically. Though the MIC values obtained for G -ve bacteria and Fungus, are large, the study proves that the class of thienopyrimidines can potentially serve as lead structure for further optimization.