Banca de QUALIFICAÇÃO: SARALINY BEZERRA FRANÇA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : SARALINY BEZERRA FRANÇA
DATE: 14/02/2022
TIME: 14:00
LOCAL: Google Meet
TITLE:

Design, synthesis and evaluation of the larvicidal activity of cinnamic acid derivatives and α-acyloxycarboxyamides against
Aedes aegypti

KEY WORDS:

Aedes aegypti, Cinnamic acid derivative, Toxicity, Designer Molecular, Biological activity.

PAGES: 90
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

Aedes aegypti is a major public health problem for transmitting a number of arboviroses, among them: dengue,
chinkunguya, and zika virus, of which studies show that zika may be related to cases of microcephaly and Guilan Barré
syndrome. In this sense, it is necessary to control this vector that affects mainly developing countries. Currently, the
control of Aedes is done through the use of insecticides, however, these forms of management have proven to be toxic,
carcinogenic and the mosquito larvae have shown resistance, requiring new forms of control more active and with
minimal adverse effects. Thus, the derivatives of cinnamic acid are described in the literature for presenting a wide
range of biological applications, including insecticidal, antimicrobial and antitumor actions, among others. Thus, due to
the various potentialities and coming from natural sources, cinnamic acid and its derivatives have been used as a model
for the synthesis of compounds with a more effective insecticidal action. In this sense, in the present work, the synthesis
of cinnamic esters was performed, by means of the Horner - Wadsworth-Emmons olefination (HWE) reaction and Fisher 

esterification, between n-substituted aromatic aldehydes with triethyl 2-phosphonopropionate, and n-substituted
cinnamic acids and thionyl chloride, respectively, leading to the formation of esters in moderate to good yields (80% -
99%). The cinnamic esters were hydrolyzed with lithium hydroxide, providing the respective cinnamic acids, which were
subjected to Passerini reaction between n-substituted aromatic aldehydes and tert-butyl isocyanide, providing the α-
acyloxycarboxyamides with yields ranging from 30 to 60%. The compounds were characterized by nuclear magnetic
resonance spectroscopic techniques of hydrogen (NMR ¹H), carbon (NMR ¹3C - DEPTQ), NOESY (Nuclear Overhauser
Enhancement Spectroscopy) and infrared (IR). The cinnamates and α-acyloxycarboxyamide derivatives were evaluated
against fourth instar larvae (L4) of Aedes aegypti, and those that showed moderate (50%>M<75%) to active (M>75%)
activity by the preliminary assay were selected for LC50 determination. The in silico study was elaborated, in which the
ethyl p-chlorocinnamate derivative of the ethyl cinnamate series had the best Score result, corroborating with the
larvicidal result (8.3 µg/mL). Thus, the ethyl p-chlorocinnamate (LC50) was selected to identify and quantify the larval
extract by HPLC-UV analysis, as well as a morphological analysis of the larva and ecotoxicological study against plant
species (Lactuca sativa, Solanum lycopersicum and Allium cepa) and vertebrate animals, such as Oreochromis niloticus
(Tilapia). From the ecotoxicological study it was possible to verify that the ethyl p-chlorocinnamate was not toxic against
plant species, as well as through the HPLC-UV analysis that showed the presence of an enzymatic hydrolysis, with the
formation of its precursor (p-chlorocinnamic acid). In addition, an efficient synthetic route led to the obtaining of α-
acyloxycarboxyamides, which allowed the formation of an unprecedented collection with potential insecticidal and
pharmacological activity.

BANKING MEMBERS:
Externo à Instituição - DANIELA MARIA DO AMARAL FERRAZ NAVARRO - UFPE
Presidente - 2089941 - DIMAS JOSE DA PAZ LIMA
Interno - 3182336 - EDEILDO FERREIRA DA SILVA JUNIOR
Interna - 1820117 - ISIS MARTINS FIGUEIREDO
Externo à Instituição - Verônica Diniz da Silva - UFAL