Banca de DEFESA: SINDY VANESA ACOSTA RODEZNO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : SINDY VANESA ACOSTA RODEZNO
DATE: 11/10/2024
TIME: 14:00
LOCAL: sala 312-3
TITLE:

Antimicrobials, antivirals, covid-19, organoselenides, organotellurides, and chalcogen compounds.

PAGES: 180
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

 

The medicinal chemistry of organochalcogen compounds, particularly those containing selenium and tellurium, is closely linked to the biological roles of selenium in living organisms. Selenium, an essential element in the amino acid selenocysteine, is a critical component of various enzymes, including glutathione peroxidase (GPx), which exhibits antioxidant properties by reducing Reactive Oxygen Species (ROS) when the chalcogen is in its divalent state (2+ oxidation state). Organoselenium and organotellurium compounds can mimic this antioxidant activity, generating significant interest and extensive research on these compounds. Recently, there has been growing attention on the bioactivity of organochalcogens in their hypervalent states (4+ oxidation state), where they function as inhibitors of enzymes dependent on endogenous thiols, such as cysteine proteases. These enzymes are therapeutic targets for infections caused by viruses, protozoa, and parasites, highlighting the importance of designing, synthesizing, and evaluating new organoselenium and organotellurium molecules with antimicrobial properties.

Our research group has previously identified promising cysteine protease inhibitors, prompting further exploration of structurally diverse organochalcogens. The current project aims to synthesize organochalcogen molecules with antimicrobial bioactivity through three phases: (I) synthesis and characterization of organochalcogen compounds, (II) biological evaluation for antimicrobial activity, and (III) structural modifications to enhance bioactivity. Initially, we synthesize organoselenides and organotellurides by functionalizing benzaldehydes with organochalcogenyl groups and boronic acids, followed by converting the formyl groups into various functional derivatives and oxidizing them to obtain hypervalent selenuranes and telluranes.

Biological evaluations revealed that tellurium-containing compounds (SV09, SV13, SV15, and SV17) exhibited significant activity against Gram-negative bacteria, including multidrug-resistant strains of E. coli, while selenium-containing compounds were inactive. Some tellurides also demonstrated antifungal activity against C. neoformans and C. albicans. Additionally, comparative cytotoxic assessments using both 2D and 3D (spheroid) NCTC cell models provided insights into the potential in vivo relevance of these compounds. These models and organoids help bridge the gap between in vitro and in vivo activities of compounds, enhancing drug screening and drug development efforts before advancing to animal models.

Finally, as part of our academic contribution to the COVID-19 pandemic, we evaluated these compounds for antiviral activity against SARS-CoV-2, whose main proteases belong to the cysteine proteases family, as well as against cysteine proteases in the Chikungunya virus. Preliminary screening identified several organochalcogens with potential antiviral activity, particularly against SARS-CoV-2 and Chikungunya, which is encouraging for further development. Among them, oxime SV11 and amines SV12 (Se) and SV13 (Te) showed potential antiviral activity, leading to further studies and structural modifications to enhance their biological activity.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1623562 - RODRIGO LUIZ OLIVEIRA RODRIGUES CUNHA
Membro Titular - Examinador(a) Externo ao Programa - 1941387 - FERNANDA DIAS DA SILVA
Membro Titular - Examinador(a) Externo à Instituição - JANAÍNA ALINE GALVAO BARROS
Membro Titular - Examinador(a) Externo à Instituição - MARCOS ANTONIO DE OLIVEIRA
Membro Titular - Examinador(a) Externo à Instituição - MARCOS LEONI GAZARINI DUTRA - UNIFESP
Membro Suplente - Examinador(a) Interno ao Programa - 1766090 - MIRELA INES DE SAIRRE
Membro Suplente - Examinador(a) Externo ao Programa - 1604147 - LEONARDO JOSE STEIL
Membro Suplente - Examinador(a) Externo ao Programa - 1272592 - JOANA MONTEZANO MARQUES
Membro Suplente - Examinador(a) Externo à Instituição - TIMOTHY JOHN BROCKSOM - UFSCAR