title: Application of "hydrogen bonding interaction" in new drug development: design, synthesis, antiviral activity, and SARs of thiourea derivatives.
abstract: A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to be important but not the more the better. The optimal compound (R,R)-20 showed the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500 μg/mL and 39%/100 μg/mL; inactivation activity, 71%/500 μg/mL and 35%/100 μg/mL; curative activity, 73%/500 μg/mL and 37%/100 μg/mL; protection activity, 69%/500 μg/mL and 33%/100 μg/mL), which is significantly higher than that of Ningnanmycin. The systematic study provides strong evidence that these simple thiourea derivatives could become potential TMV inhibitors.
authors.affiliation: School of Marine Science and Engineering, Hebei University of Technology , Tianjin 300130, China.
authors.forename: Aidang
authors.initials: A
authors.lastname: Lu
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006860:Hydrogen Bonding; D010935:Plant Diseases / Q000821:virology; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry*; D014026:Nicotiana / Q000821:virology; D014027:Tobacco Mosaic Virus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D013890:Thiourea
keywords: SARs; anti-TMV activity; nature product; thiourea derivatives; tobacco mosaic virus