HIV-1 reverse transcriptase inhibitors from family zingiberaceae

Abstract

Eleven medicinal plants in the Zingiberaceae family were extracted with water and methanol and then screened for inhibition of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 rt) and proteases from human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and human cytomegalovirus (HCMV). The results showed that most of the methanol extracts have strong inhibition of the three different proteases, especially methanol extract of Kaempferia parviflora and Alpinia galanga. Kaempferia parviflora and Alpinia galanga were isolated to identify chemical constituents by using bioassay-guided as a navigator of fractionation. Eight flavonoids (1-8) were isolated from Kaempferia parviflora and compounds 9-11 were isolated from Alpinia galanga. The structures of the isolated compounds were determined by spectroscopic techniques. The effects of each compound in inhibiting three different proteases were tested. It was found that 5-hydroxy-7-methoxyflavone (2) and 5,7-dimethoxyflavone (7) showed a potent inhibitory activity against HIV-1 protease, both with IC[subscript 50] values of 19 micromolar. Moreover, 5-hydroxy-3,7-dimethoxyflavone (1) posses a mild inhibitory activity against HCV protease and HCMV protease with the IC[subscript 50] value of 190 and 250 micromolar, respectively. While 4-hydroxycinnamaldehyde (10) showed HIV-1 protease inhibitory effect with IC[subscript 50] value of 130 micromolar, and HCMV protease inhibitory effect with IC[subscript 50] value of 97 micromolar. In addition, 4-methoxy cinnamic acid ethyl ester (13) and 4-methoxy cinnamic acid (14) which isolated from Kaempferia galanga showed the highest activity against alpha-glucosidase inhibition among the trans-cinnamic acid derivatives with IC[subscript 50] value of 0.05 and 0.04 mM, respectively