Banca de QUALIFICAÇÃO: RODOLFO ANDRE DE ARAUJO SANTOS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : RODOLFO ANDRE DE ARAUJO SANTOS
DATA : 19/12/2017
HORA: 09:00
LOCAL: SALA 2 DO PPGCF
TÍTULO:

Activity Cliff as a toll in Structure Activity Relationship for FabH Inhibitors.

PALAVRAS-CHAVES:

β-cetoacil-ACP sintase III; Penhascos de Atividade Biológica

PÁGINAS: 60
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

The synthesis of fatty acids, mainly by the enzyme β-ketoacyl-ACP synthase III (FabH), has been emerging as an excellent target for new molecules with antimicrobial action. Despite the urgency generated by increasing bacterial resistance, the synthesis of new molecules is a very expensive task both in time and in financial resources. In this sense, using the infor-mation contained in the ligands, already synthesized, to extract the maximum information of the affinity for the receivers, is configured as an alternative of low operational cost. The best way to extract this information from ligands is to realize that parts of these molecules best contribute to biological activity. However, when faced with such different molecular skele-tons, it becomes difficult to perceive which parts best contribute to biological activity. In this way, it is the small differences in very similar molecules that best define the regions of the molecule, and the inhibitor, which contribute most to biological activity. The relationship between this group of molecules is known as biological activity cliffs. In view of all the ad-vantages exposed, this methodology was chosen to guide the synthesis of new inhibitors of the FabH enzyme through the understanding of which regions of the enzyme are most im-portant in the definition of biological activity. From this study, concluded that proposition of new candidates for inhibitors of the enzyme FabH should favor the choice of polar groups in two distinct regions of the active site. Molecules that make hydrogen bonds with the amino acids of the catalytic triad have their activity increased by up to two orders of magnitude, in addition to this, substituents with greater capacity for interaction with the amino acids Argi-nine 36, Arginine 151 and Tryptophan 32 tend to increase the activity of the target molecule. Finally, in addition to guiding the synthesis of certain groups in potential new inhibitors, there is a need to direct efforts in understanding and increasing accuracy in docking studies performed for molecules without defined crystallographic structure.

MEMBROS DA BANCA:
Externo ao Programa - 1714867 - CAIO LIMA FIRME
Presidente - 1871916 - RAQUEL BRANDT GIORDANI
Externo ao Programa - 2379057 - VANESSA ALMEIDA OTELO