Natural product-based semisynthesis and biological evaluation of thiol/amino-Michael adducts of xanthatin derived from Xanthium strumarium as potential pesticidal agents

• Published in: Bioorganic chemistry Vol. 97; pp. 103696 - 103706
• Main Authors: Zhi, Xiao-yan, Jiang, Ling-yun, Li, Ting, Song, Li-li, Wu, Li-juan, Cao, Hui, Yang, Chun
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.04.2020; Elsevier
• Subjects: Amination; Antifungal activity; Biochemistry & Molecular Biology; Botrytis - drug effects; Chemistry; Chemistry, Organic; Fungicides, Industrial - chemical synthesis; Fungicides, Industrial - chemistry; Fungicides, Industrial - toxicity; Furans - chemical synthesis; Furans - chemistry; Furans - toxicity; Larvicidal activity; Life Sciences & Biomedicine; Models, Molecular; Natural products-based pesticides; Ovicidal activity; Physical Sciences; Plant Diseases - microbiology; Plant Diseases - prevention & control; Science & Technology; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - toxicity; Xanthatin; Xanthium - chemistry; Xanthium strumarium; Antifungal activity; Larvicidal activity; Ovicidal activity; Natural products-based pesticides; Xanthatin; Xanthium strumarium; DESIGN; L; DISCOVERY; SESQUITERPENE LACTONES; XANTHANOLIDES; ANTICANCER; ANTIFUNGAL ACTIVITIES; AMINO-DERIVATIVES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103696

[Display omitted] •Forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized.•Compounds 2c, 2h, 2i, and 2t exhibited excellent antifungal activity.•Derivatives 2b, 7g, and 7h demonstrated significant ovicidal activity.•The structure-activity relationships (SARs) were also discussed. Xanthatin, a natural sesquiterpene lactone, occurs as one of the major constituents of Xanthium plants (Compositae) and exhibits many important biological properties. To discover natural products-based pesticides, forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized and characterized, while their pesticidal activities were investigated. Among them, compounds 2c, 2h, 2i, and 2t exhibited more potent antifungal activity against Botrytis cinerea (IC50 = 0.96, 0.38, 6.33, and 7.21 µg/mL, respectively) than xanthatin and the two commercial fungicides. Compounds 2t and 2u displayed broad-spectrum and excellent antifungal effects against all tested phytopathogenic fungi, while their IC50 values ranged from 7.21 to 75.88 µg/mL. Compounds 2a, 2f, 2l, 2m, 2v, 7c, 7e, 7h, 7i, and 7j showed moderate larvicidal activity against Plutella xylostella Linnaeus. Furthermore, compounds 2b, 7g, and 7h demonstrated significant ovicidal activity against P. xylostella with the LC50 values of 14.04, 10.00, and 11.95 mg/L, respectively. These findings suggest that thiol/amino appended in the C-13 position of xanthatin may improve antifungal and ovicidal activities for the derivatives. It was also noticed that the exocyclic double bond of xanthatin is crucial for its larvicidal activity. This work also provides some important hints for further design, synthesis, and structural modification of the xanthanolides sesquiterpene lactones toward development of the new environmentally friendly pesticides for sustainable agricultural production.