Thymol as an Interesting Building Block for Promising Fungicides against Fusarium solani

• Published in: Journal of agricultural and food chemistry Vol. 69; no. 25; pp. 6958 - 6967
• Main Authors: Alves Eloy, Mariana, Ribeiro, Rayssa, Martins Meireles, Leandra, Antonio de Sousa Cutrim, Thiago, Santana Francisco, Carla, Lirian Javarini, Clara, Borges, Warley de Souza, Costa, Adilson Vidal, Queiroz, Vagner Tebaldi de, Scherer, Rodrigo, Lacerda, Valdemar, Alves Bezerra Morais, Pedro
• Format: Journal Article
• Language: English
• Published: American Chemical Society 30-06-2021
• Subjects: Agricultural and Environmental Chemistry; black pepper root rot; Fusarium solani; agrochemicals; thymol derivatives; triazole
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.0c07439

The semisynthesis of 15 new thymol derivatives was achieved through Williamson synthesis and copper-catalyzed azide–alkyne cycloaddition (CuAAC) approaches. The reaction of CuAAC using the “Click Chemistry” strategy, in the presence of an alkynyl thymol derivative and commercial or prepared azides, provided nine thymol derivatives under microwave irradiation. This procedure reduces reaction time and cost. All molecular entities were elucidated by 1H and 13C NMR, IR, and HRMS data. These derivatives were evaluated in vitro for their fungicidal activity against Fusarium solani sp. Among the nine triazolic thymol derivatives obtained, seven of them were found to have moderated antifungal activity. In contrast, naphthoquinone/thymol hybrid ether 2b displayed activity comparable with that of the commercial fungicide thiabendazole. The structure–activity relationship for the most active compound 2b was discussed, and the mode of action was predicted by a possible binding to the fungic ergosterol and interference of osmotic balance of K+ into the extracellular medium.