Banca de QUALIFICAÇÃO: CAMILA DA SILVA NUNES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : CAMILA DA SILVA NUNES
DATE: 12/05/2023
TIME: 09:30
LOCAL: Google Meet
TITLE:

Evaluation of the interaction of aminoguanidine hydrazones and derivatives with mutated and normal DNA: application in the treatment of leshimaniasis

KEY WORDS:

Interaction, DNA, aminoguanidine hydrazones, spectroscopic techniques, molecular docking

PAGES: 54
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

Leishmaniasis is a neglected disease caused by parasites, which affects mainly the low-income population, representing yet one of the main causes of mortality worldwide. There is currently no vaccine against this disease and, in addition, the first-choice treatment against the symptoms in Brazil is based on pentavalent antimonial. Aminoguanidine hydrazones (AGH's) constitute a class of compounds that extends itself into a wide variety of structures and design of new compounds structurally related with antileishmania activity. Studies on DNA compounds are also carried out to investigate their leishmanicidal activity, producing promising results with DNA as the main target. Based on this, the present work aimed to evaluate the in vitro interaction between ct-DNA and eight compounds derived from AGH's, using spectroscopic techniques, in addition to docking studies, molecular dynamics and ADMET properties. During the studies of molecular fluorescence, the compounds subject to analysis exhibited emission at 450 nm when excited at 317 nm. Therefore, due to the variation in the intrinsic fluorescence of the compound, it was possible to evaluate the Stern-Volmer constant (Ksv) and the binding constant (Kb), which were close to 105 L mol-1 . Furthermore, it has been shown that the preferential quenching mechanism for the fluorescence of compounds by ctDNA is static quenching. Competition studies (acridine orange, ethidium bromide, DAPI, hoechst) provided means to observe that these compounds interact with DNA preferentially via groove. Additionally, regarding the results of molecular docking, the compounds presented a binding affinity in the range of -6.6 kcal mol-1 , via groove interactions, forming hydrogen bonds with DNA residues DC15 and DG16. In addition, the ADMET properties of these compounds were evaluated, observing the rules of Lipinski, Veber and Egan. In this sense, it was observed that the compounds analyzed showed promising results regarding the interaction with DNA.

BANKING MEMBERS:
Presidente - 1820117 - ISIS MARTINS FIGUEIREDO
Interno(a) - 2089941 - DIMAS JOSE DA PAZ LIMA
Interno(a) - 2343745 - JULIO COSME SANTOS DA SILVA
Externo(a) ao Programa - 1461121 - SILVIA HELENA CARDOSO