Naturally occurring Vpr inhibitors from medicinal plants of Myanmar

Abstract

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.

Keywords: Isopimarane diterpenoids; K. pulchra; P. javanica; Picrasane quassinoids; TREx-HeLa-Vpr cells; Viral protein R.

Fig. 1

Structures of compounds isolated from K. pulchra rhizomes

Fig. 2

The inhibitory effects of a the CHCl₃-soluble extract of K. pulchra and b the potent compounds and the positive control damnacanthal against the expression of Vpr in TREx-HeLa-Vpr cells

Fig. 3

Structures of compounds isolated from P. javanica bark

Fig. 4

The inhibitory effects of a the CHCl₃-soluble extract of P. javanica and b the isolated compounds and the positive control damnacanthal against the expression of Vpr in TREx-HeLa-Vpr cells