Abstract

A novel series of 2,5-disubstituted-1,3,4-oxadiazole analogs (4a-j) was synthesized starting from 2-aminopyrimidine. A computational study was carried out for the molecular properties prediction and none of the compounds violated Lipinski “Rule of 5”. The structures of the compounds were confirmed on the basis of their spectral data and the purity of the compounds was checked by elemental analysis. Some of the compounds were screened for in vitro anticancer activity as per National Cancer Institute (NCI US) Protocol on leukemia, melanoma, lung, colon, CNS, ovarian, renal and prostate and breast cancer cell lines. N-{[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]methyl}pyrimidin-2- amine (4a) showed maximum activity with growth percent of 61.19 (UO-31; Renal cancer) and 76.82 (MCF; Brest Cancer). The antibacterial and antifungal activities were evaluated as per the standard protocol reported elsewhere. N-{[5-(4- aminophenyl)-1,3,4-oxadiazol-2-yl]methyl}pyrimidin-2-amine (4e) showed maximum antibacterial activity among the series, comparable to the standard drug ciprofloxacin with MIC ranging from 4-8 µg/mL while N-{[5-(3,4- dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]methyl}pyrimidin-2-amine (4g) showed maximum antifungal activity among the series, less active than the standard drug fluconazole with MIC 4 µg/mL.

Keywords: Anticancer, Antibacterial, Antifungal, Molecular properties prediction, Oxadiazole, Pyrimidine.

Graphical Abstract