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具有抗1型人类免疫缺陷病毒和人巨细胞病毒体外活性的植物源和半合成的咖伦内酯化合物。

Plant-derived and semi-synthetic calanolide compounds with in vitro activity against both human immunodeficiency virus type 1 and human cytomegalovirus.

作者信息

Xu Z Q, Kern E R, Westbrook L, Allen L B, Buckheit R W, Tseng C K, Jenta T, Flavin M T

机构信息

MediChem Research and Sarawak MediChem Pharmaceuticals, Lemont, IL 60439, USA.

出版信息

Antivir Chem Chemother. 2000 Jan;11(1):23-9. doi: 10.1177/095632020001100102.

Abstract

Plant-derived and semi-synthetic calanolide compounds with anti-human immunodeficiency virus type 1 (HIV-1) activity were tested for anti-human cytomegalovirus (HCMV) activity in both cytopathic effect inhibition and plaque reduction assays. The results indicated that the anti-HCMV activity of calanolide compounds does not correlate with their activity against HIV-1. The semi-synthetic 12-keto derivatives tended to be more active against HCMV than the corresponding 12-OH congeners, which were more active against HIV-1. It appeared that the 7,8-unsaturated double bond in the chromene ring played a certain role in maintaining activities against both HCMV and HIV-1. Saturation of the double bond increased the EC50 values against both viruses, with concomitant increase in toxicity. The calanolide compounds reported here are the first non-nucleoside analogues capable of inhibiting both HIV-1 and HCMV and, therefore, may be useful chemoprophylactic agents for HCMV in HIV-infected people or vice versa.

摘要

对具有抗1型人类免疫缺陷病毒(HIV-1)活性的植物源和半合成的可乐果内酯化合物进行了细胞病变效应抑制试验和蚀斑减少试验,以检测其抗人巨细胞病毒(HCMV)的活性。结果表明,可乐果内酯化合物的抗HCMV活性与其抗HIV-1活性不相关。半合成的12-酮衍生物对HCMV的活性往往比相应的12-羟基同系物更高,而后者对HIV-1的活性更高。色烯环中的7,8-不饱和双键似乎在维持对HCMV和HIV-1的活性方面发挥了一定作用。双键饱和会增加对两种病毒的半数有效浓度(EC50)值,同时毒性也会增加。本文报道的可乐果内酯化合物是首批能够同时抑制HIV-1和HCMV的非核苷类似物,因此,它们可能是用于HIV感染者预防HCMV的有用化学预防剂,反之亦然。

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