New phorbol ester derivatives as potent anti-HIV agents
| Autor: | Yung Yi Cheng, Qi-Run Li, Masuo Goto, Kuo‐Hsiung Lee, Susan L. Morris-Natschke, Daofeng Chen, Jian Zhang, Xiao-Lei Huang, Ya-Dong Cui, Xiao-Gang Jiang, Chin Ho Chen, Lei Zhao |
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| Rok vydání: | 2021 |
| Předmět: |
Anti-HIV Agents
Cell Survival Stereochemistry Clinical Biochemistry Pharmaceutical Science Potential candidate Antineoplastic Agents Virus Replication Biochemistry Phorbol ester Structure-Activity Relationship Cell Line Tumor Phorbol Esters Drug Discovery Side chain Humans Potency Cytotoxicity Molecular Biology Molecular Structure Anti hiv Chemistry Organic Chemistry Cell culture HIV-1 Molecular Medicine Selectivity |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 50:128319 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2021.128319 |
| Popis: | Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials. |
| Databáze: | OpenAIRE |
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