[Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl-calanolide A].
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.
Peng
Zong-Gen
ZG
Institute of Medicinal and Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Chen
Hong-Shan
HS
Wang
Lin
L
Liu
Gang
G
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000821:virology; D039681:Pyranocoumarins / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism
C543509:11-demethylcalanolide A; D019380:Anti-HIV Agents; D007106:Immune Sera; D039681:Pyranocoumarins; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C075959:calanolide A