Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety

Molecules

Zhihua Wan²  Deyu Hu¹  Pei Li²  Dandan Xie²  Xiuhai Gan² 

[1] State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, Guizhou Province, China;

关键词: 4-thioquinazoline derivatives;    chalcone moiety;    synthesis;    antiviral activity;    TMV;    3D-QASR;    MST;   

DOI  :  10.3390/molecules200711861

来源: mdpi

【 摘 要 】

A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M₂ and M₆ possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC₅₀) values of 138.1 and 154.8 μg/mL, respectively, which were superior to that of Ribavirin (436.0 μg/mL). The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR) of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR) method of comparative molecular field analysis (CoMFA) based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q² and non-cross-validated r² values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST) experimental showed that the compound M₆ may interaction with the tobacco mosaic virus coat protein (TMV CP).

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.