Analysis of the cytotoxicity and genotoxicity of an indole derivative and its formulation with larvicidal activity against Aedes aegypti Linn: control of dengue, chikungunya and Zika.

• Grant number: 22/05657-7
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Edson Luis Maistro
• Grantee: Edson Luis Maistro
• Host Institution: Faculdade de Filosofia e Ciências (FFC). Universidade Estadual Paulista (UNESP). Campus de Marília. Marília , SP, Brazil
• Associated researchers: Clélia Akiko Hiruma Lima ; Gisela de Aragão Umbuzeiro ; Sócrates Cabral de Holanda Cavalcanti

Abstract

The reintroduction of the mosquito Aedes aegypti Linn. in Brazil in the 80's started a period of dissemination of diseases transmitted by this mosquito. Upon every new serotype or disease introduced in this country, new epidemics arise. Recently, two new diseases transmitted by this mosquito were introduced in Brazil, namely chikungunya and Zika. Especially, Zika has alarmed health authorities worldwide due to its sexually-transmitting capabilities, microcephaly in newly born babies, and the Guillain-Barré syndrome. These data show that there is an urge to deepen the research not only for treating these diseases, but also to control its mosquito vector. Considering the resistance that the larvae of A. aegypti have developed to the larvicides currently used, the development of studies aimed at obtaining effective compounds against the larvae of this mosquito vector are of fundamental importance for human society. In this context, our research group synthesized N-tosylindole, a molecule with sufficient larvicidal potency to be directed to pharmacotechnical development studies. To carry out the studies that are being proposed, this project initially aims to carry out the synthesis on a larger scale of the compound in question, analyzes of its cytotoxic and genotoxic potential, LD50 determination in rodents, followed by the development of a formulation for its use, as well as its residual effect. A part of cellular and genetic toxicity analyzes will be carried out in sphedoids of HepG2/C3A human hepatoma cells, with extension to analyzes of effects on the cell cycle, apoptosis and expression of genes involved in these metabolic pathways. Nanotechnology will be used to obtain a formulation, aiming to increase the effectiveness of vector control and enable the use of a molecule with low water solubility, N-tosylindole, making this product viable for use in water. A suitable formulation must release the larvicide continuously in order to maintain the concentration of the larvicide at a high enough level to maintain its effect for a long time. The residual effect will be obtained in laboratory aiming to determine the number of days its active ingredient stays in the environment in which it was placed. This same study can be increased to a semi-field scale, evaluating the residual effect in conditions more similar to reality in semi-field evaluation using containers in the environment. Then the formulation will be evaluated for impacts on non-target plant species via evaluation of N-tosylindole effects on germination and plant growth. At the end of the project, it is expected that the data collected will allow the use of the molecule in question as a larvicide and serve as another tool in the control of the A. aegypti mosquito and in the fight against the diseases vectored by it. (AU)