Application of "Hydrogen-Bonding Interaction" in Drug Design. Part 2: Design, Synthesis, and Structure-Activity Relationships of Thiophosphoramide Derivatives as Novel Antiviral and Antifungal Agents.
On the basis of the structure of natural product harmine, lead compound 18, and the structure of compounds in part 1, a series of thiophosphoramide derivatives 1-17 were designed and synthesized from various amines in one step. Their antiviral and antifungal activities were evaluated. Most of the compounds showed significantly higher antiviral activity against tobacco mosaic virus (TMV) than commercial virucide ribavirin. Compound (R,R)-17 showed the best anti-TMV activity in vitro (70%/500 μg/mL and 33%/100 μg/mL) and in vivo (inactivation effect, 68%/500 μg/mL and 30%/100 μg/mL; curative effect, 64%/500 μg/mL and 31%/100 μg/mL; protection effect, 66%/500 μg/mL and 31%/100 μg/mL), which is higher than that of ningnanmycin and lead compound 18. The antiviral activity of (R,R)-17·HCl is about similar to that of (R,R)-17. However, the antifungal activity of (R,R)-17·HCl against Puccinia sorghi is slightly lower than that of (R,R)-17. The systematic study provides compelling evidence that these simple thiophosphoramide compounds could become efficient antiviral and antifungal agents.
School of Marine Science and Engineering, Hebei University of Technology , Tianjin 300130, People's Republic of China.
Aidang
A
Lu
School of Marine Science and Engineering, Hebei University of Technology , Tianjin 300130, People's Republic of China.
Yuanyuan
Y
Ma
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education, College of Chemistry, Tianjin Normal University , Tianjin 300387, People's Republic of China.
Ziwen
Z
Wang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, People's Republic of China.
Zhenghong
Z
Zhou
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, People's Republic of China.
Qingmin
Q
Wang
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D006860:Hydrogen Bonding; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects
D000935:Antifungal Agents; D000998:Antiviral Agents
Puccinia sorghi; SARs; anti-TMV activity; antifungal activity; thiophosphoramide derivatives; tobacco mosaic virus