Shizukaol F: a new structural type inhibitor of HIV-1 reverse transcriptase RNase H.
- Author:
Ying YANG
1
;
Ying-li CAO
;
Hai-yang LIU
;
Huan YAN
;
Ying GUO
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Cell Line, Tumor;
Drugs, Chinese Herbal;
chemistry;
isolation & purification;
pharmacology;
HEK293 Cells;
HIV Reverse Transcriptase;
metabolism;
HIV-1;
physiology;
Humans;
Inhibitory Concentration 50;
Magnoliopsida;
chemistry;
Molecular Structure;
Plants, Medicinal;
chemistry;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
pathology;
Reverse Transcriptase Inhibitors;
chemistry;
isolation & purification;
pharmacology;
Ribonuclease H;
antagonists & inhibitors;
metabolism;
Sesquiterpenes;
chemistry;
isolation & purification;
pharmacology;
Virus Replication;
drug effects
- From:
Acta Pharmaceutica Sinica
2012;47(8):1011-1016
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the mechanism of action of lindenane disesquiterpenoid shizukaol F on HIV-1 replication. Real time quantity PCR, ELISA assay and fluorescence methods were used to test HIV-1 reverse transcription process, RNA-dependent DNA polymerase activity, and RNase H activity, respectively. It showed that shizukaol F inhibited LTR/Gag production of HIV-1 reverse transcription with an IC50 of 9.11 micromol x L(-1). This result is consistent with its inhibitory effect on HIV-1 replication (IC50 of 6.12 micromol x L(-1)). Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT-RNase H with IC50 of 26.4 micromol x L(-1), but had no effect on HIV-1 RT RNA-dependent DNA polymerase activity. In conclusion, shizukaol F is a new structural type HIV-1 RNase H inhibitor. This discovery will provide a clue for new type of reverse transcriptase inhibitors development.
