Heterocyclic lactam derivatives containing piperonyl moiety as potential antifungal agents.

To study the novel functionalized heterocyclic molecules with highly potential biological activity, two series of heterocyclic lactam derivatives containing the piperonyl moiety were designed and synthesized. The newly obtained compounds have been identified on the basis of analytical spectral data, including ¹H NMR, ¹³C NMR, and ESI-MS. The target compounds were evaluated for their potential antifungal activities in vitro against twelve species of the plant pathogen fungi (Sclerotinia sclerotiorum, Rhizoctonia solani, Rap Sclerotinia stemrot, Fusarium graminearum, Phomopsis adianticola, Pestallozzia theae, Pestalotiopsis guepinii, Alternaria tenuis Nees, Monilinia fructicola, Colletotrichum gloeosporioides, Phytophthora capsici, Magnaporthe oryzae). Preliminary bioassays suggested that all prepared compounds I1-14 displayed broad-spectrum and moderate antifungal activities compared with the positive control hymexazol, especially for Sclerotinia sclerotiorum, Rap Sclerotinia stemrot, and Monilinia fructicola. In particular, the inhibition rate of compound I9 exhibited good inhibition activity reached 95.16% against Sclerotinia sclerotiorum, and compounds I5, I12 against Phytophthora capsici were 93.44%, 91.25%. Further studies revealed that compounds I5 (IC₅₀ = 19.13 µM) and I12 (IC₅₀ = 9.12 µM) exhibited obviously antifungal activities against Phytophthora capsici, which were better than that of commercial agricultural fungicide hymexazol (IC₅₀ = 325.45 µM). Therefore, these target compounds could be further studied and explored as a lead skeleton for discovery of novel antifungal agents.