Win Nwet Nwet, Ngwe Hla, Abe Ikuro, Morita Hiroyuki
Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama, 930-0194, Japan.
Department of Chemistry, University of Yangon, Yangon, 11041, Myanmar.
J Nat Med. 2017 Oct;71(4):579-589. doi: 10.1007/s11418-017-1104-7. Epub 2017 Jul 5.
Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.
人类免疫缺陷病毒1型(HIV-1)是慢病毒家族的成员,它编码逆转录病毒的Gag、Pol和Env蛋白,以及另外六种辅助蛋白,即Tat、Rev、Vpu、Vif、Nef和Vpr。目前已批准的抗HIV药物靶向Pol和Env编码的蛋白。然而,这些药物仅在降低病毒复制方面有效。此外,药物的毒性和耐药菌株的出现已成为全球范围内的严重问题。最终,所有已批准的抗HIV药物,包括新批准的靶向HIV整合酶(IN)的药物,都会产生耐药性。耐药性可能是由于病毒复制过程中发生的自发突变而产生的。因此,必须开发出能有效阻断其他病毒成分的新药,以降低耐药率并在几乎没有或没有长期毒性的情况下抑制病毒复制。辅助蛋白可能会扩展治疗选择。病毒蛋白R(Vpr)是HIV辅助蛋白中有前景的药物靶点之一。然而,在抗HIV药物研发中,对抑制剂的寻找仍在继续。在本综述中,我们总结了从两种缅甸药用植物中发现的天然化合物及其构效关系。从艳山姜根茎和爪哇苦树树皮中总共分离出49种次生代谢产物,化合物类型分别被鉴定为异海松烷二萜和苦树苦木素类。在这些分离物中,发现7种二萜和15种苦木素类是缺乏可检测毒性的Vpr抑制剂,它们的效力根据各自的功能而有所不同。