Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor

Abstract

Scrotonin receptors (5-HTRs), especially the 5-HT1A subtype, have been the subject of intensive research for the past decade, due to their function in human physiology. Several structurally different classes of ligands are known to bind to the 5-HT1A receptor, but arylpiperazine derivatives are among the most important ligands. In the work, docking analyses were used to explain the binding affinities of a series of ligands with different N-1 substituent. All ligands had ill common the arylpiperazine structure, while the N-1 substituent was modified to investigate the influence of ligand structure on its binding affinity. The shape and size, as well as the rigidity of the substituents were altered to investigate the possible effects on the formation of the receptor - ligand complex.

Serotoninski receptori su, a naročito 5-HT 1A pod tip, zbog značajne uloge u fiziologiji ljudskog organizma, predmet intenzivnog izučavanja tokom protekle decenije. Poznato je da se za 5-HT 1A receptor vezuje nekoliko strukturno različitih klasa liganada, ali su arilpiperazinski derivati među najznačajnijim. Da bi objasnili vezivanje serije liganada sa različitim N-1 supstituentima za receptor koristili smo analizu vezivanja (docking analizu). Svi ligandi su imali zajedničku arilpiperazinsku strukturu dok su im N-1 supstituenti modifikovani tako što je menjan oblik, veličina kao i krutost supstituenta da bi se istražio njihov eventualni uticaj na formiranje kompleksa receptor - ligand.