Ultrasound-Assisted Synthesis, Antifungal Activity against Fusarium oxysporum, and Three-Dimensional Quantitative Structure–Activity Relationship of N,S-Dialkyl Dithiocarbamates Derived from 2-Amino Acids

A high-yielding, green, and fast synthesis of alkyl 2-substituted {[(alkylsulfanyl)carbonothioyl]amino}acetate-type compounds is described. The one-pot, three-component condensation of alkyl 2-aminoesters, carbon disulfide, and electron-deficient olefins was the key reaction to be developed. The products were obtained easily and efficiently, with good overall yields after two steps (79-91%), employing short reaction times, without the use of a catalyst, and ultrasonic irradiation in water. This procedure was exploited to produce antifungals against the phytopathogenic fungus Fusarium oxysporum . Some synthesized compounds exhibited good performance as mycelial growth inhibitors (IC 50 < 80 μM). Structural and antifungal datasets were integrated to explore the comprehensive three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and explain the observed activity. This integration resulted in an excellent CoMFA model ( r 2 = 0.812; q 2 = 0.771) after substructure-based alignment. According to this model, synthesized compounds possessing steric bulky electron-withdrawing groups in the dithiocarbamate moiety can be considered as promising F. oxysporum inhibitors.