Synthesis and Chemometrics of Thymol and Carvacrol Derivatives as Larvicides against Aedes aegypti

Viviane Barros Silva; Daniele Lima Travassos; Angelita Nepel; Andersson Barison; Emmanoel Vilaça Costa; Luciana Scotti; Marcus Tulius Scotti; Francisco Jaime Bezerra Mendonça-Junior; Roseli La Corte Dos Santos; Sócrates Cabral de Holanda Cavalcanti

Synthesis and Chemometrics of Thymol and Carvacrol Derivatives as Larvicides against Aedes aegypti

J Arthropod Borne Dis. 2017 May 27;11(2):315-330. eCollection 2017 Jun.

Affiliations

¹ Medicinal Chemistry Laboratory, Pharmacy Department, Federal University of Sergipe, São Cristóvão, Brazil.
² Nuclear Magnetic Resonance Laboratory, Chemistry Department, Federal University of Paraná, Curitiba, Brazil.
³ Chemistry Department, Institute of Sciences, Federal University of Amazonas, Manaus, Brazil.
⁴ Biotechnology Center, Federal University of Paraíba, Campus I, João Pessoa, Brazil.
⁵ Laboratory of Synthesis and Delivery of Molecules, Biological Sciences Department, State University of Paraíba, João Pessoa, Paraiba, Brazil.
⁶ Parasitology and Tropical Entomology Laboratory, Morphology Department, Federal University of Sergipe, São Cristóvão, Brazil.

PMID: 29062856
PMCID: PMC5641620

Abstract

Background: Thymol and carvacrol have previously demonstrated larvicidal activity against Aedes aegypti (Diptera: Culicidae). In view of this fact, it was of our interest to obtain synthetic derivatives and evaluate their larvicidal activity on Ae. aegypti larvae.

Methods: Structural modifications were performed on thymol and carvacrol in an effort to understand the functional groups necessary for modulating their activities and to lead possibly to more effective larvae control agents. The derivatives were further subjected to SAR and computational studies (molecular modeling and chemometric tools (CPCA and PCA)) to extract structural information regarding their larvicidal properties. Field collected and Rockefeller populations of Ae. aegypti were used.

Results: Carvacrol and thymol exhibited LC₅₀ of 51 and 58ppm for field collected larvae, respectively. Carvacrol derivatives exhibited LC₅₀ ranging from 39 to 169ppm, while thymol derivatives exhibited LC₅₀ ranging from 18 to 465ppm. Substitution of the acidic proton of carvacrol by esters, ethers, and acetic acid resulted in either maintenance or reduction of potency.

Conclusion: Thymol derivatives were, to a certain extent, more efficient larvicides against Ae. aegypti than carvacrol derivatives, particularly to Rockefeller larvae. The chemometrics tools applied in this study showed that the independent variables indicate a mixed profile. Nevertheless, hydrophobic interactions increased the larvicidal activity.

Keywords: Carvacrol derivatives; Chemometry; Dengue; SAR; Thymol derivatives.