Discovery of N-Substituted Indole Derivatives Incorporating 1,3,4-Thiadiazole Thioether and Amide Moieties as Antibacterial Agents

A series of indole derivatives containing 1,3,4-thiadiazole thioether and amide moieties were designed, synthesized and evaluated for their in vitro antibacterial activities against Pseudomonas syringae pv. Actinidiae (Psa), Xanthomonas axonopodis pv. Citri (Xac) and Xanthomonas oryzae pv. Oryzae (Xoo). The preliminary antibacterial evaluation of the target compounds showed N-[5-(benzylthio)-1,3,4-thiadiazol-2-yl]-2-(1H-indol-1-yl)acetamide, N-{5-[(2-fluorobenzyl)thio]-1,3,4-thiadiazol-2-yl}-2-(2-methyl-1H-indol-1-yl)acetamide, 2-(3-methyl-1H-indol-1-yl)-N-{5-[(3-methylbenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide and 2-(3-acetyl-1H-indol-1-yl)-N-{5-[(3-methylbenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide possessed excellent antibacterial activity against Psa, compounds N-{5-[(4-bromobenzyl)thio]-1,3,4-thiadiazol-2-yl}-2-(3-methyl-1H-indol-1-yl)acetamide, 2-(3-methyl-1H-indol-1-yl)-N-{5-[(4-(trifluoromethyl)benzyl]thio}-1,3,4-thiadiazol-2-yl)acetamide and 2-(3-acetyl-1H-indol-1-yl)-N-{5-[(4-methylbenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide displayed outstanding inhibitory effects against Xoo. 2-(1H-Indol-1-yl)-N-{5-[(3-methylbenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide, 2-(3-methyl-1H-indol-1-yl)-N-{5-[(3-methylbenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide and 2-(3-acetyl-1H-indol-1-yl)-N-{5-[(4-bromobenzyl)thio]-1,3,4-thiadiazol-2-yl}acetamide displayed significant inhibitory effects against Xac. These derivatives synthesized in our laboratory exhibit promising activity against detrimental plant-pathogenic bacteria.