摘要
本文比较研究消旋11-去甲胡桐素A[(±)-11-demethyl-calanolide A]和其母体消旋胡桐素A[(±)-calanolide A]在体外、细胞培养内和小鼠体内给药后血清的抗HIV-1(human immunodeficiency virus type 1)活性。二者在体外对HIV-1逆转录酶(reverse transcriptase,RT)的半数抑制浓度(IC50)分别为(3.028±2.514)μmol.L-1和(3.965±5.235)μmol.L-1。在HIV-1感染的MT-4细胞培养内抑制HIV-1细胞病变的IC50和选择指数分别为(1.081±0.337)μmol.L-1和26及(1.297±0.076)μmol.L-1和21。腹腔注射小鼠1次(100 mg.kg-1)后30 min和60 min的血清对HIV-1 RT的抑制率前者分别为(42.7±1.5)%和(32.2±6.1)%,后者分别为(40.7±6.3)%和(29.2±6.7)%,说明消旋11-去甲胡桐素A为新非核苷类HIV-1逆转录酶抑制剂,比其母体消旋胡桐素A的抗HIV-1活性略高,值得进一步研究。
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 · 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） μmol· L^-1 and （3. 965 ±5. 235） μmol · L^-1, and also inhibited CPE in HIV-1 ⅢB infected MT-4 cell cultures with IC50 of （1. 081 ± 0. 337） μmol · L^-1 and （ 1. 297 ± 0. 076） μmol · L^-1, respectively. After intraperitoneal injection of 100 mg · 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 30min （P〈0.01） and （32.2±6. 1）% at 60min （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 （ ± ）-ll-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.
出处
《药学学报》
CAS
CSCD
北大核心
2008年第5期456-460,共5页
Acta Pharmaceutica Sinica
