Design, synthesis and fungicidal activities of phenazine-1-carboxamida conjugates of 1,3,4-thia(oxa)diazole

Phenazine-1-carboxylic acid (PCA), isolated from Pseudomonas, is a very important fungicidal agent. PCA and its derivatives revealed good biological activities in the field of medicine and agrichemicals. In this paper, two series of PCA derivatives containing 1,3,4-thiadiazole and 1,3,4-oxadiazole were designed and synthesized to explore novel fungicidal candidates. Their in vitro and in vivo fungicidal activities were evaluated. The title compounds I ₈ (X=S, R=2-OCH₃) and I ₂₂ (X=O, R=2-OCH₃) had EC₅₀ vaues of 33.25 μg/mL and 46.52 μg/mL against Fusarium graminearum, respectively, which were about 3-4 times better than of PCA (EC₅₀ = 128.54 μg/mL). In vivo results showed that compounds I ₈ and I ₂₂ gave better bioactivity (inhibitory rates of 58.69% and 55.37% at 500 μg/mL, respectively) against F. graminearum than that of PCA (25.14%). Preliminary structure-activity relationship study found that the introduction of electron-donating groups were favored to improving the activity of the derivatives, and the substitution at ortho-position of benzene ring would be favored to fungicidal activity. The substitution position of the same substituent on the benzene ring was in the order of o > p > m according to the bioactivity.These results can be used to guide the further structural modification of these compounds for novel fungicidal agent.