Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl-calanolide A.
- Author:
Zong-Gen PENG
1
;
Hong-Shan CHEN
;
Lin WANG
;
Gang LIU
Author Information
1. Institute of Medicinal and Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-HIV Agents;
pharmacology;
Cell Line, Tumor;
Female;
HIV Reverse Transcriptase;
antagonists & inhibitors;
metabolism;
HIV-1;
drug effects;
Humans;
Immune Sera;
pharmacology;
Inhibitory Concentration 50;
Male;
Mice;
Molecular Structure;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
pathology;
virology;
Pyranocoumarins;
chemistry;
pharmacology;
Reverse Transcriptase Inhibitors;
pharmacology;
Stereoisomerism
- From:
Acta Pharmaceutica Sinica
2008;43(5):456-460
- CountryChina
- Language:Chinese
-
Abstract:
To compare the anti-HIV-1 activities of (+/-)-11-demethyl-calanolide A and its mother compound (+/-)-calanolide A in vitro and in vivo, the inhibitory activities of the two compounds on HIV-1 reverse transcriptase (RT) were detected in vitro with isotope 3H assay. The cytotoxicity and inhibition of cytopathic effect (CPE) were studied in HIV-1 IIIB infected MT-4 cell cultures by MTT staining method; Mice were given with the two compounds 100 mg x kg(-1) once intraperitoneally, then the mouse sera taken on 30 min and 60 min after administration were detected for the inhibition of HIV-1 RT in vitro. The data showed that (+/-)-11-demethyl-calanolide A and (+/-)-calanolide A inhibited HIV-1 RT in vitro with 50% inhibitory concentration (IC50) of (3.028 +/- 2.514) micromol x L(-1) and (3.965 +/- 5.235) micromol x L(-1), and also inhibited CPE in HIV-1 IIIB infected MT-4 cell cultures with IC50 of (1.081 +/- 0.337) micromol x L(-1) and (1.297 +/- 0.076) micromol x L(-1), respectively. After intraperitoneal injection of 100 mg x kg(-1) of the two compounds in mice, all the mice sera taken 30 and 60 min afterward inhibited HIV-1 RT in vitro. In comparison with control mice sera, the inhibitory rates of the sera for (+/-)-11 -demethyl-calanolide A were (42.7 +/- 1.5)% at 30 min (P < 0.01) and (32.2 +/- 6.1)% at 60 min (P < 0.05), separately, while the inhibitory rates of the sera for (+/-)-calanolide A were (40.7 +/- 6.3)% at 30 min (P < 0.01) and (29.2 +/- 6.7)% at 60 min. The results suggested that (+/-)-11-demethyl-calanolide A is a new non-nucleoside HIV-1 RT inhibitor, its anti-HIV-1 activities in vitro, in cell cultures and in mice were slightly higher than that of its mother compound (+/-)-calanolide A and warrants further studies.
