Banca de DEFESA: KARLLY THAYANNY DE OLIVEIRA PEREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : KARLLY THAYANNY DE OLIVEIRA PEREIRA
DATE: 30/08/2024
TIME: 14:00
LOCAL: GOOGLE MEET
TITLE:

Exploring the study of interactions between macromolecules and
organic compounds: evaluation of biological targets, fluorescent
probes for nucleic acids, and urease inhibitors.

KEY WORDS:

Biomolecules; bioactive compounds; interaction; DNA; BSA;
RNA; fluorescent probes; enzyme inhibition; urease

PAGES: 155
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

In recent decades, several studies have been carried out on the
interaction of biomolecules with bioactive compounds, since this
knowledge enables various applications associated with the
development of new biologically active compounds and
fluorescent probes for clinical use, quantification of biomolecules
and enzyme inhibition. The limitations existing in methods and
compounds already reported in the literature or in commercial
use indicate that studies are still needed to obtain more active
molecules with better biological properties, thus making it
necessary to search for more efficient systems capable of
meeting these needs. In this sense, this work was developed in
three parts. The first consisted of evaluating the interaction of
biologically active compounds (pisosterol and its derivatives Pd-
1 and Pd-2) with ctDNA (Calf Thymus) and BSA (bovine serum
albumin), where the preferential binding mode via groove and a
greater affinity of interaction with pisosterol for DNA were
verified. The main forces that stabilized the macromolecule-
ligand complexes were hydrogen bonds and van der Walls
forces. In the second part, the interaction of eight molecules (5a-

b, 8a-b, 9a-b and 12a-b) with DNA/RNA was evaluated for the
development of fluorescent probes (off-on), and it was observed
that in the presence of nucleic acids the analytical signal
increased significantly compared to the analytical blank.
Compound 5a showed the greatest analytical sensitivity, with the
optimum conditions being when the concentration of the
probewas equal to 3 µM, in 100 mM HEPES buffer (pH = 7). It
was applied to real saliva, urine and semen samples and
quantitative recoveries were observed, as well as the possibility
of qualitative application using UV radiation. These compounds
therefore have the potential to be used as off-on fluorescent
probes for the detection and quantification of nucleic acids.
Finally, the third part explored the enzymatic inhibition of
imidazopyridine (3a-b and 4a-b) and imizadopirimidine (3c-d and
4c-d) derivatives against Canavalia ensiformis (Jack bean)
urease. Compound 3b was the most active (lowest IC50 value).
Kinetic studies showed that this compound acts as a mixed-type
inhibitor, having a preferential allosteric binding site, where the
main forces governing the interaction were hydrogen bonds and
van der Walls forces. In the test with real soil samples, a
complex system, the compound maintained its inhibitory
capacity. In view of the above, it is possible to state that this
work contributes to advances in the understanding of
interactions between macromolecules and small molecules,
providing a basis for the development of systems with better
biological properties and practical applications in the
development of biologically active molecules, detection and
quantification of biomolecules and enzyme inhibitors.

COMMITTEE MEMBERS:
Externo(a) à Instituição - Ana Paula Silveira Paim - UFPE
Interno(a) - 1869296 - CINTYA D'ANGELES DO ESPIRITO SANTO BARBOSA
Externo(a) à Instituição - FRANCISCO ANTÔNIO DA SILVA CUNHA - UFBA
Presidente - 1820117 - ISIS MARTINS FIGUEIREDO
Interno(a) - 1006306 - JADRIANE DE ALMEIDA XAVIER
Interno(a) - 1613338 - JOSUE CARINHANHA CALDAS SANTOS