Banca de DEFESA: RODOLFO ANDRE DE ARAUJO SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : RODOLFO ANDRE DE ARAUJO SANTOS
DATA : 30/05/2018
HORA: 14:00
LOCAL: SALA 1 DO PPGCF
TÍTULO:

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

PALAVRAS-CHAVES:

β-cetoacil-ACP sintase III; FABH; ACTIVITY CLIFF

PÁGINAS: 98
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 in time and in financial resources. In this sense, to use the information contained in the binders, already synthesized, to extract the maximum information of the affinity for the targets, is configured as an alternative of low operational cost for the directed development of new active compounds. An effective way of extracting this information from ligands is to realize that parts of these molecules best contribute to biological activity. However, when faced with such different molecular skeletons, it becomes difficult to perceive such factors. Thus, it is the small differences in fairly similar molecules that best define the regions of the molecule, and the inhibitor, which contribute to increased potency. The relationship between this group of molecules is known as Activity Cliff. In view of all the advantages exposed, this methodology was chosen to guide the synthesis of new inhibitors of the FabH enzyme. From this study, it was possible to determine pharmacophore components that can guide the design of new inhibitors of the FabH enzyme. Hydrogen donor groups in the catalytic region of the active site, together with bulky groups that increase the contact surface with the catalytic triad allied to electron acceptor groups close to the amino acids arginine 249, arginine 36 and asparagine 210 were the perceived factors for the increase of the activity. Finally, quinoline-like groups that can interact with the amino acids arginine 151, tryptophan 32 in an additional side pocket and make hydrogen bonds with the amino acid threonine 28.

MEMBROS DA BANCA:
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA
Externo à Instituição - MARCUS TULLIUS SCOTTI - UFPB
Externo ao Programa - 2379057 - VANESSA ALMEIDA OTELO