Banca de DEFESA: RITA DE KASSIA OLIVEIRA DA COSTA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : RITA DE KASSIA OLIVEIRA DA COSTA
DATE: 06/11/2025
TIME: 14:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

Bioactive molecules analogous to stigmurine with antimicrobial, antibiofilm, and healing actions

KEY WORDS:

Antimicrobial peptide; Biofilm; Cytotoxicity; Antifungal activity; Wound healing;

Molecular dynamics; In sílico.

PAGES: 96
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Antimicrobial resistance has become increasingly alarming given the risks it poses to the global

economy and public health. The irrational use of antimicrobials has contributed greatly to this

microbial resistance to conventional drugs. Given this problem and the chronic nature of

infections with and by biofilm formation in skin wounds, antimicrobial peptides (AMPs)

emerge as promising alternatives for the development of new drugs. It was through changes in

the amino acid chain of Stigmurina (FFSLIPSLVGGLISAFK-NH₂), designed by our research

group using bioinformatics, that the analogous peptides StigA15 (FFSLIPKLVGGLIKAFK

NH₂) and StigA28 (FFKLIPKLVGKLIKAFK-NH₂) emerged. In this context, the objective of

the study was to obtain data on the applicability of biomolecules in biological, antimicrobial,

and healing activity. StigA15 and StigA28 are analog peptides of Stigmurine, a peptide found

in the venom of the scorpion Tityus stigmurus. The analogues correspond to promising PAMs

obtained through rational molecule design. In this study, pharmacokinetic activity was

evaluated by predictive analysis using the pkCSM server and predictive molecular dynamics

simulation (in silico) of interaction in the peptide-membrane system, in addition to cytotoxicity

by cell viability analysis with reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl

tetrazolium (MTT), antibacterial activity by broth microdilution, inhibition of biofilm

formation in a 96-well microplate for bacteria and fungi (in vitro), and healing activity in

uninfected surgical wounds on the backs of Swiss mice (in vivo). The substitutions of glycine

for lysine increased the net charge of the analogues, reduced cytotoxicity, intensified the

peptide-microorganism interaction, and conferred promising antimicrobial activity to both

peptides tested against different Gram-positive, Gram-negative bacteria, and yeasts. As a result,

favorable peptide-membrane interaction was observed for the analog peptides through

molecular dynamics, corroborating the results of a spectrum of amplification of the favorable

action of PAMs both in the minimum inhibitory concentration (MIC) and in the antibiofilm

activity for Staphylococcus aureus (ATCC 25923) at different concentrations between 2.8 μM,

especially in the late phase, in addition to a positive healing effect on uninfected wounds at a

concentration of 1 mg/ml. The peptides StigA15 and StigA28 demonstrated potent

antimicrobial activity against Gram-positive (2.8 μM - 46.22 μM) and Gram-negative (2.1 μM

- 8.5 μM) bacteria and yeasts of the genus Candida spp. (1.32 μM – 14.42 μM) at non-cytotoxic

concentrations. In addition, they exhibited bactericidal and fungicidal effects, indicating a broad

spectrum of action. In murine models, they also promoted the healing of skin wounds,

suggesting their potential as bioactive agents with dual functions: antimicrobial and healing.

COMMITTEE MEMBERS:
Externo à Instituição - ENEAS DE CARVALHO - IB/SP
Externa à Instituição - KARLA SAMARA ROCHA SOARES - UFPB
Presidente - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA