Phenoxy, Phenylthio 및 Benzyloxy-기가 치환된 Quinolone 유도체들의 항트리파노소마 활성에 대한 3D-QSAR 분석

3D-QSAR Analysis on the Antitrypanosomal Activity of Phenoxy, Phenylthio or Benzyloxy Group Substituted Quinolone Analogues

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model (q2=0.528 and r2=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in R4 and R5 position and sterically disfavored groups were located in R2 position. Also, the positively charged groups on R2 would be able to increase the antitrypanosomal activities.