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3D-QSAR Studies of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones Derivatives as RSV Fusion Inhibitors

[ Vol. 15 , Issue. 3 ]

Author(s):

Lian Liu, Yuanhao Zhai, Yiqun Chang, Wen Yan, Ruoshi Huang, Pinghua Sun, Wenzhu Huang* and Jialiang Guo*   Pages 304 - 315 ( 12 )

Abstract:


Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory- tract infections (ALRI) in young children, elderly and high-risk adults and results in considerable hospitalizations. The fusions of RSV were proved to be a potent target in combating virus.

Methods: A series of newly reported isoindol-5-ones derivatives as RSV fusion inhibitors was studied via in silico methodologies 3D-QSAR (CoMFA and CoMSIA) to explore compounds with better activity. Internal and external cross-validation techniques were investigated.

Results: Satisfactory CoMFA model (q2=0.542, r2=0.908) and CoMSIA model (q2=0.563, r2=0.874) were obtained. The external validation indicated that CoMFA and CoMSIA models possessed high predictive powers with Q2 F2 values of 0.734 and 0.701, respectively. The contour maps shows the bulky, and hydrogen bond acceptor groups at R2 position are essential to improve the antivirus activity. The minor and hydrophobic groups such as ether bond at para-position or metaposition of substituent group R1 may increase their activities.

Conclusion: The plots of CoMFA and CoMISA provided information of the structure–activity relationship and revealed the chemical features affecting the antivirus activity. These results expand our understanding of RSV fusion inhibitors and could be helpful in rationally designing of new analogs with more potent inhibitory activities.

Keywords:

RSV fusion inhibitors, QSAR, Isoindol-5-ones, ALRI, pneumonia, respiratory diseases.

Affiliation:

School of Stomatology and Medicine, Foshan University, Foshan 528000, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, The Fifth People's Hospital of Foshan City, Foshan 528211, School of Stomatology and Medicine, Foshan University, Foshan 528000, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, The Fifth People's Hospital of Foshan City, Foshan 528211, School of Stomatology and Medicine, Foshan University, Foshan 528000

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