A study on the synthesis and biological evaluation of some 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 2,5-disubstituted-1,3,4-oxadiazoles

Abstract

The 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,3,4-oxadiazoles are prominent biological agents used as a cure against a number of human ailments. The present work deals with the synthesis of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4- thiadiazoles and 2,5-disubstituted-1,3,4-oxadiazoles bearing adamantyl and aryl moieties. The synthesis of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles was carried out starting from aryl carboxylic acids. On the other hand, 2,5-disubstituted-1,3,4-oxadiazoles were synthesized using two distinct routes starting from either aryl carboxylic acids or aryl nitriles. The structures of the synthesized compounds were confirmed by IR, 1 H- and 13 C-NMR, EIMS and XRD analysis. The target compounds were screened for their antitumor, antiviral, antibacterial and antifungal potential. Among the tested compounds, 3-(2-methylphenyl)-6-adamantyl- 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (4a) and 3-(2-fluorophenyl)-6-adamantyl-1,2,4- triazolo[3,4-b]-1,3,4-thiadiazole (4d) exhibited prominent antiproliferative activity against human CD4 + T-cells containing an integrated HTLV-1 genome (MT-4) with CC 50 of 45 μM and 47 μM, respectively. These compounds were also found to be active against human acute T-lymphoblastic leukemia (CCRF-CEM) cell lines with CC 50 of 40 μM each. 3-(3-Methylphenyl)-6-adamantylmethyl-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazole (4n) showed moderate inhibition of HIV-1 and HIV-2 with EC 50 of >10.90 μg/mL, but no selectivity could be witnessed. Similarly, 3-(3-methylphenyl)- 6-adamantylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (5n) was found to be potent exhibiting moderate inhibition of HIV-1 and HIV-2 with EC 50 of >10.86 μg/mL. Furthermore, oxadiazole (9a) and 2-adamantyl-5-(2-(2-methylphenyl)-1,3-thiazol-4-yl)-1,3,4- 2-adamantyl-5-(2-(2-bromophenyl)-1,3-thiazol-4-yl)-1,3,4- oxadiazole (9j) showed significant inhibition of HIV-1 and HIV-2 with EC 50 of >10.50 μg/mL and >10.90 μg/mL, respectively. However, antibacterial and antifungal activities of all the compounds were found to be non-significant at non-toxic concentrations.