Design, Synthesis, and Evaluation of Thiazole-Monoterpene Hybrids as Potential Novel Fungicides

Introduction: Plant pathogenic fungi pose a serious threat to global agricultural production, and the widespread use of traditional fungicides is limited due to resistance issues, necessitating the development of novel molecules to address this challenge. Cyclic monoterpenes and thiazol derivatives have a wide range of biological activities. Method: Twenty novel 2-(thiazol-4-yl)acetic acid derivatives bearing cyclic monoterpene moieties were synthesized via cyclization, hydrolysis, and esterification. Their fungicidal activities were tested using the poisoned medium method. Result: Compounds 4a and 4b exhibited significant inhibitory effects against Curvularia mebaldsii, with EC50 values of 28.3 and 27.2 mg/L, respectively, outperforming the control agent hymexazol (EC50 = 66.7 mg/L). Additionally, 4e demonstrated 85.1% inhibition against Rhizoctonia solani at 80 mg/L, showing comparable efficacy to hymexazol. Discussion: Thekyl substitution at the 2-position of the thiazole ring in this class of compounds is more favorable for enhancing fungicidal activity. Specifically, bulky groups tend to reduce the fungicidal activity of the compounds. Conclusion: Compounds 4a, 4b, and 4e were discovered as potential lead compounds for the design of fungicides. This finding provides valuable insights into the design of thiazole-based fungicides incorporating cyclic monoterpenes, offering a scientific foundation for developing novel fungicidal agents.