# Design and Synthesis of Thymol Derivatives Bearing a 1,2,3-Triazole Moiety for Papaya Protection against Fusarium solani

## TL;DR

Researchers designed new thymol-based fungicides to protect papayas from a fungal disease, showing better binding and potential effectiveness than existing fungicides.

## Contribution

A novel series of thymol derivatives with 1,2,3-triazole moieties were synthesized and shown to bind more effectively to a key fungal enzyme.

## Key findings

- Twenty thymol derivatives were synthesized and tested for antifungal activity against Fusarium solani.
- Molecular docking showed the derivatives had lower binding energy than tebuconazole and lanosterol in the FsCYP51 enzyme.
- The compounds likely inhibit ergosterol production by blocking the enzyme's active site and entrance tunnel.

## Abstract

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 Fusarium solani, 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 F. solani lanosterol 14α-demethylase (FsCYP51) enzyme.
Docking results demonstrated that all derivatives bound to the catalytic
pocket of FsCYP51 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 FsCYP51 by
these derivatives, thereby blocking lanosterol and its conversion
into ergosterol.