Author/Authors :
Barros Silva, Viviane Medicinal Chemistry Laboratory - Pharmacy Department - Federal University of Sergipe, São Cristóvão, Brazil , Travassos, Daniele Lima Medicinal Chemistry Laboratory - Pharmacy Department - Federal University of Sergipe, São Cristóvão, Brazil , Nepel, Angelita Nuclear Magnetic Resonance Laboratory - Chemistry Department - Federal University of Paraná, Curitiba, Brazil , Barison, Andersson Nuclear Magnetic Resonance Laboratory - Chemistry Department - Federal University of Paraná, Curitiba, Brazil , Costa, Emmanoel Vilaça Chemistry Department - Institute of Sciences - Federal University of Amazonas, Manaus, Brazil , Scotti, Luciana Biotechnology Center - Federal University of Paraíba, Campus I, João Pessoa, Brazil , Scotti, Marcus Tulius Biotechnology Center - Federal University of Paraíba, Campus I, João Pessoa, Brazil , Mendonça-Junior, Francisco Jaime Bezerra Laboratory of Synthesis and Delivery of Molecules - Biological Sciences Department - State University of Paraíba, João Pessoa, Paraiba, Brazil , dos Santos, Roseli La Corte Parasitology and Tropical Entomology Laboratory - Morphology Department - Federal University of Sergipe, São Cristóvão, Brazil , de Holanda Cavalcanti, Sócrates Cabral Medicinal Chemistry Laboratory - Pharmacy Department - Federal University of Sergipe, São Cristóvão, Brazil
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 :
Chemometry , SAR , Dengue , Thymol derivatives , Carvacrol derivatives
