Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl-calanolide A
Peng, Z-Gen.; Chen, H-Shan.; Wang, L.; Liu, G.
Yao Xue Xue Bao 43(5): 456-460
2008
ISSN/ISBN: 0513-4870 PMID: 18717330 Document Number: 618778
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 H-3 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 center dot 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) mu mol center dot L-1 and (3.965 +/- 5.235) mu mol center dot L-1, and also inhibited CPE in HIV-1 IIIB infected MT-4 cell cultures with IC50 of (1.081 +/- 0.337) mu mol center dot L-1 and (1.297 +/- 0.076) mu mol center dot L-1, respectively. After intraperitoneal injection of 100 mg center dot 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-ealanolide 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.