Synthesis, Antifungal Activity, and QSAR Studies of Benzbutyrolactone Derivatives Based on α-Methylene-γ-butyrolactone Scaffold

α-Methylene-γ-butyrolactone scaffold and benzofuran pharmacophore demonstrate a number of valuable medicinal properties. Based on bioactivity-guided mixed synthesis principle, we have designed and synthesized a series of new derivatives combining these two substructures. Antifungal activity of the products against some pathogenic fungi and cytotoxicity has been tested. QSAR has been performed. All зкщвгсеы demonstrate high activity against B. cinerea and G. graminis. Compounds with the 4-fluorophenyl group and compound connected with the cinnamic aldehyde structure demonstrate superior in vitro and in vivo activity. Results of SARs and QSAR studies exhibit that the lower electron density around the α-methylene-γ-butyrolactone backbone structure and smaller steric hindrance on the exocyclic carbon-carbon double bond are beneficial for antifungal activity. The results indicate benzbutyrolactone derivatives with α-methylene-γ-butyrolactone and benzofuran pharmacophore as highly active low-toxic compounds with the fungicide potential potential.