Banca de DEFESA: SARALINY BEZERRA FRANÇA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : SARALINY BEZERRA FRANÇA
DATE: 24/01/2024
TIME: 14:00
LOCAL: Sala de reuniões do IQB
TITLE:

Design, synthesis and evaluation of the larvicidal, antimicrobial, Leishmania amazonensis and ecotoxicological activity of cinnamic acid derivatives.

KEY WORDS:

Acid cinnamic and derivatives; Organic synthesis; Biological assessment; In silico study, Ecotoxicity.

PAGES: 170
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

Cinnamic acid and its natural or synthetic derivatives have numerous biological applications, such as: antineoplastic, inhibitory, antimicrobial, antileishmanicidal, antioxidant, larvicidal and others. Their cinnamic structure is responsible for these therapeutic actions, as it has several reactive sites that contribute to the interaction with the associated target. In addition, DAC’s have low toxicity and can be used in cosmetics and food. These compounds act through different mechanistic pathways, one of the characteristics of which is that they are good candidates for combating neglected and multidrug-resistant diseases, whether by killing microorganisms of the Candida genus, the most varied forms of Leishmania or hosts such as Aedes aegypti, This is a good strategy for developing bioactive molecules that are more potent than those found on the market, since these have been shown to be toxic, carcinogenic, teratogenic and most microorganisms, protozoa and hosts are already resistant. Thus, due to their diverse biological activities and because they come from natural sources, cinnamic acid and its derivatives have been used as a model for the synthesis of compounds with more effective insecticidal action. In this sense, this work reports efficient methods for synthesizing DAC's, including: Horner-Wadsworth-Emmons (HWE) olefination reaction, acid esterification, alkaline hydrolysis and Passerini (Multicomponent) reaction, respectively, obtaining n-substituted cinnamic compounds in good yields, in which six α-acyloxycarboxyamides are new to the literature. The cinnamate derivatives and αacyloxycarboxyamides were evaluated against the fourth instar larvae (L4) of Aedes aegypti, and those that showed moderate (between 50 and 75%) to active (> 75%) activity in the preliminary assay were selected for CL50 determination. The in silico study carried out showed that the ethyl p-chlorocinnamate derivative, from the ethyl cinnamate series, scored best, corroborating its larvicidal activity result (CL50 = 8.3 µg/mL). Thus, ethyl pchlorocinnamate was selected to identify and quantify the larval extract using HPLC analysis, as well as a morphological analysis of the larva and an ecotoxicological study on the plant species (Lactuca sativa, Solanum lycopersicum and Allium cepa). From the ecotoxicological study, it was possible to conclude that ethyl pchlorocinnamate was not toxic to the plant species, and through HPLC analysis, the presence of p-chlorocinnamic acid was observed, suggesting enzymatic metabolization. This study was confirmed by the enzymatic inhibition of AChE present in the larval extract of the Ae. aegypti vector by the n-substituted cinnamic esters, which had a larvicidal action. In addition, the esters and n-substituted cinnamic acids were subjected to an antifungal study against Candida albicans and Candida neoformans, proving to be active with MICs ranging from 0, 24mM to 2.26mM, with ethyl (2E,4E)-5-phenylpenta-2,4-dienoate (0.24mM, SFD2) standing out against Candida albicans and pchlorocinnamic acid (0.27mM) against Candida neoformans. The majority of the α-acyloxycarboxyamides showed low cytotoxicity in peritoneal macrophages (CC50> 400µM), making them of low toxicity. Furthermore, in the analysis of both promastigote and amastigote forms, it was found that the majority showed leishmanicidal activity, with the compounds SFD4 (CI50> 31.83µM and CI50 >27.28µM) and SFD10 (CI50> 33.88µM and CI50 >38.31µM) standing out, respectively. These, in turn, showed a good selectivity index (SI), being above the minimum allowed (SI>10), with SFD4 standing out with a SI > 14.66. Therefore, these results suggest that the DACs are good candidates for insecticides and their structural scaffold can be used to design antifungal and antileishmanicidal candidates, since they have low toxicity against other non-target organisms.

COMMITTEE MEMBERS:
Externo(a) à Instituição - DANIELA MARIA DO AMARAL FERRAZ NAVARRO - UFPE
Interno(a) - 2089941 - DIMAS JOSE DA PAZ LIMA
Interno(a) - 3182336 - EDEILDO FERREIRA DA SILVA JUNIOR
Interno(a) - 1006306 - JADRIANE DE ALMEIDA XAVIER DOS SANTOS
Interno(a) - 1294906 - RUTH RUFINO DO NASCIMENTO
Externo(a) ao Programa - 1461121 - SILVIA HELENA CARDOSO - null