Banca de QUALIFICAÇÃO: ESTELA MARIANA GUIMARÃES LOURENÇO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ESTELA MARIANA GUIMARÃES LOURENÇO
DATE: 27/01/2020
TIME: 14:00
LOCAL: SALA 2 DO PPGCF
TITLE:

Identification of a Selective PDE4B Inhibitor From Bryophyllum pinnatum by Target Fishing Studyand In Vitro Evaluation of Quercetin3-O-a-LArabinopyranosyl-(1→2)-O-a-LRhamnopyranoside

KEY WORDS:

Computer aided-drug design, organic synthesis, PDE4B, flavonoids.

PAGES: 109
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

The development of organic synthesis represents an important advance in the discovery of new drugs, being considered an important step in medicinal chemistry. However, the process of obtention and optimization of drugs is considered a challenge task. The high costs and laboratory time involved in this process are result of the absence of direction pathways and prioritization of the synthesis of new compounds without a previously established pharmacological activity. The use of computer aided-drug design using prototypes is considered an important tool, capable to generate more directional pathway for synthesis. In association to this, the prospection of natural products has a long history in drug discovery and is still a source of unprecedented prototypes. Recently, a glycosylated flavonoid capable of selectively inhibit the enzyme PDE4B has been discovered. This target can be highlighted as promising alternative in the treatment of diseases as asthma and chronical obstructive pulmonary disease. Nonetheless, the structure of the flavonoid has some structural challenges that prevent it from being considered a potential drug. The present study aims to design and synthesize new potential selective inhibitors of PDE4 enzyme using the discovered flavonoid as a prototype. Therefore, it was used structure-activity relationship informations of a series of known inhibitors that had demonstrated the importance of polar groups to make intermolecular interactions in M and S pockets, as well as an aromatic ring occupying the Q pocket of the enzyme. Additionally, molecular dynamics studies and binding free energy calculations made possible the determination of two potential binding modes of the flavonoid. Considering these features, hypothesis responsible for the selectivity profile were suggested based on differences in flexibility of the proteins. With these informations, analogs with accessible synthetic route were proposed. With these informations, structural analogues that can be obtained by an accessible synthetic route have been proposed. The compounds are in the process of obtaining. The results generated in this study may contribute to the discovery of new drug prototypes for the treatment of chronic lung deficiency and asthma using PDE4B inhibitors.

BANKING MEMBERS:
Externo ao Programa - 1571756 - ALESSANDRO KAPPEL JORDAO
Presidente - 2330188 - GERLANE COELHO BERNARDO GUERRA
Interna - 1871916 - RAQUEL BRANDT GIORDANI