Design and Synthesis of Thymol Derivatives Bearing a 1,2,3-Triazole Moiety for Papaya Protection against <i>Fusarium solani</i>
Azole-based fungicides are among the market's most widely used and effective agents. However, their indiscriminate use can lead to reduced efficacy and increased pathogen resistance. This highlights the need for novel fungicides that offer improved efficiency and lower environmental impact for controlling phytopathogenic fungi. In this study, a series of 20 novel thymol derivatives, incorporating a 1,2,3-triazole moiety, were synthesized via a three-step process, with the key step being the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The antifungal activity of these compounds was evaluated against <i>Fusarium solani</i>, the etiological agent of papaya fruit and stem rot. Additionally, molecular docking was performed to assess the binding energy and interaction modes of these derivatives with the <i>F. solani</i> lanosterol 14α-demethylase (<i>Fs</i>CYP51) enzyme. Docking results demonstrated that all derivatives bound to the catalytic pocket of <i>Fs</i>CYP51 with lower binding energy (<-10 kcal/mol) compared to the azole fungicide tebuconazole (-8.2 kcal/mol) and the substrate lanosterol (-9.0 kcal/mol). The observed fungicidal activity is likely due to the occupancy of the entrance tunnel and active site of the <i>Fs</i>CYP51 by these derivatives, thereby blocking lanosterol and its conversion into ergosterol.
Authors
- Leandra Martins Meireles (ORCID: https://orcid.org/0000-0003-0289-3669)
- Eduardo S. G. Mizubuti (ORCID: https://orcid.org/0000-0001-9612-5155)
- Cláudia Jorge do Nascimento (ORCID: https://orcid.org/0000-0001-8896-8654)
- Adílson Vidal Costa (ORCID: https://orcid.org/0000-0002-7968-8586)
- Luiz C. A. Barbosa (ORCID: https://orcid.org/0000-0002-5395-9608)
- Willian Bucker Moraes (ORCID: https://orcid.org/0000-0001-7478-7772)
- Pedro Alves Bezerra Morais (ORCID: https://orcid.org/0000-0001-5501-7350)
- Róbson Ricardo Teixeira (ORCID: https://orcid.org/0000-0003-3181-1108)
- Valdemar Lacerda (ORCID: https://orcid.org/0000-0002-8257-5443)
- J. Junker (ORCID: https://orcid.org/0000-0003-4002-4405)
- Osmair Vital de Oliveira (ORCID: https://orcid.org/0000-0001-9463-2567)
- Vagner Tebaldi de Queiroz (ORCID: https://orcid.org/0000-0002-8170-125X)
- Demetrius Profeti (ORCID: https://orcid.org/0000-0003-4565-3331)
- Wanderson Romão (ORCID: https://orcid.org/0000-0002-2254-6683)
- Rodrigo Scherer (ORCID: https://orcid.org/0000-0001-7656-0248)
- Poliana Aparecida Rodrigues Gazolla (ORCID: https://orcid.org/0000-0002-0613-9092)
- Waldir Cintra de Jesús (ORCID: https://orcid.org/0000-0001-5711-0268)
- Mariana Belizário de Oliveira (ORCID: https://orcid.org/0000-0002-5341-2151)
- Nayara A. dos Santos (ORCID: https://orcid.org/0000-0003-2754-2013)
- Danilo Aniceto da Silva
- Pedro Henrique de Andrade Barrela
Institutions
- Federal Institute of São Paulo (BR)
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal de Viçosa (BR)
- Universidade Federal de São Carlos (BR)
- Brazilian National Association of Graduate Programs in Communication (BR)
- Universidade Vila Velha (BR)
- Universidade Federal do Espírito Santo (BR)
- Fundação Oswaldo Cruz (BR)
- Universidade Federal do Estado do Rio de Janeiro (BR)
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1021/acs.jafc.4c12770
- Primary Topic
- Papaya Research and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Fundação de Amparo à Pesquisa e Inovação do Espírito Santo