Design, synthesis and preliminary antibacterial evaluation of novel 1,3-benzoxazole/carboximidamide- and 1,3-benzoxazole/3-aryl-1,2,4-oxadiazole hybrids

Two series of 1,3-benzoxazole/carboximidamides 5a-i and 1,3-benzoxazole/3-aryl-1,2,4-oxadiazoles 6a-i were prepared from the reactions of (1,3-benzoxazol-2-ylthio)acetic acid (2) with the corresponding arylamidoximes 4a-i using excess N,N'-carbonyldiimidazole (CDI). The antibacterial studies revealed that hybrid 5a demonstrated exceptional activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, with inhibition zones measuring 34 mm and 36 mm, respectively. Moreover, hybrid 5a proved strong antibacterial activity against the against Gram-negative Klebsiella pneumoniae with inhibition zone equal to 32 mm. on the other hand, hybrid 5a displayed moderate activity against Gram-negative Escherichia coli, resulting in a 15 mm inhibition zone. Hybrid 6e (with 4-methoxyphenyl) was the most potent hybrid against B. subtilis, S. aureus and K. pneumoniae with inhibition zones equal to 32, 36 and 34 mm, respectively, followed by hybrids 6b (with 4-chlorophenyl) with inhibition zones equal to 31, 34 and 35 mm, respectively. Moreover, hybrid 5a exhibited strong antibacterial activity against B. subtilis, S. aureus and K. pneumoniae with minimum inhibitory concentration (MIC) values of 1.97, 0.97 and 3.90 μM, respectively, while hybrid 6b showed strong antibacterial activity with MIC values of 7.81, 3.90 and 3.90 μM, respectively, and hybrid 6e demonstrated antibacterial activity with MIC values of 3.90, 0.97 and 1.95 μM, respectively.