SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA.
We synthesized a series of acylhydrazone compounds bearing naturally occurring amino acids' side chains as HIV assembly inhibitors. Biological evaluation indicated that the compounds had anti-SIV and capsid assembly inhibitory activities. The structure-activity relationship (SAR) study showed that compounds bearing proper aromatic side chains had potential antiviral activities. The molecular modeling experiments revealed the molecular mechanism that they could bind to CA in the same manner as CAP-1 and occupy two more grooves.
Jin
Yinxue
Y
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, PO Box 261, Beijing 100191, China.
Tan
Zhiwu
Z
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, PO Box 261, Beijing 100191, China.
He
Meizi
M
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, PO Box 261, Beijing 100191, China.
Tian
Baohe
B
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, PO Box 261, Beijing 100191, China.
Tang
Shixing
S
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Hewlett
Indira
I
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Yang
Ming
M
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, PO Box 261, Beijing 100191, China.
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015497:HIV-1 / Q000187:drug effects*; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D006835:Hydrazones