ABSTRACT
Two new hopane type triterpenes, named dryopteric acids A (1) and B (2), were isolated from the Rhizome of Dryopteris crassirhizoma (Aspiadaceae) together with sixteen known compounds (3-18). Of isolated compounds, ursolic acid (15), and dryopteric acid A (1) and B (2) showed potent inhibitory activities against HIV-1 protease with IC50 values of 8.9-44.5 microM. In addition, acetylated compounds 1 and 2 appreciably increased inhibitory activities with their IC50 values of 1.7 and 10.8 microM, respectively.
Subject(s)
Dryopteris/chemistry , HIV Protease Inhibitors/pharmacology , HIV-1/enzymology , Triterpenes/chemistry , HIV-1/drug effects , Indicators and Reagents , Mass Spectrometry , Plant Roots/chemistry , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Triterpenes/isolation & purificationABSTRACT
Triterpenoids and flavonoids isolated from Alnus firma S. Z. were found to inhibit HIV-1 virus replication and controlled its essential enzymes. In this study, the inhibition of HIV-1 viral replication and its essential enzymes, such as reverse transcriptase, protease and alpha-glucosidase, were observed using 18 Korean plant extracts. Among the extracts, the methanol extract of Alnus firma leaves showed potent inhibition against the HIV-1 induced cytopathic effect (CPE) in MT-4 cells on microscopic observation (the minimum concentration for complete inhibition of HIV-1 induced CPE, IC=50 microg/mL). Thus, 14 compounds were isolated and identified from the methanol extract of Alnus firma leaves. Of these compounds, the alnustic acid methyl ester exhibited inhibition against HIV-1 protease, with an IC50 of 15.8 microM, and quercetin, quercitrin and myricetin 3-O-beta-D-galactopyranoside displayed inhibition against HIV-1 reverse transcriptase, all with IC50 values of 60 microM. Based on these results, the viral replication inhibition of the methanol extract of Alnus firma leaves was adjudged to be acutely related to the protease inhibition activation of the alnustic acid methyl ester as well as the reverse transcriptase inhibition activation of flavonoids.
Subject(s)
Alnus/chemistry , Anti-HIV Agents/isolation & purification , Flavonoids/isolation & purification , HIV-1 , Triterpenes/isolation & purification , Anti-HIV Agents/pharmacology , Cell Line , Cell Survival , Chromatography, High Pressure Liquid , Cytopathogenic Effect, Viral , Flavonoids/pharmacology , Glycoside Hydrolase Inhibitors , HIV Protease/metabolism , HIV Protease Inhibitors/isolation & purification , HIV Protease Inhibitors/pharmacology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/drug effects , HIV-1/enzymology , HIV-1/physiology , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Triterpenes/pharmacology , Virus Replication/drug effects , alpha-GlucosidasesABSTRACT
To identify substances with anti-human immunodeficiency virus (HIV) activity from plant sources, 12 extracts of Rosa family plants were screened for their inhibitory effects against HIV-1 protease. Of the extracts tested, the strongest inhibitory effects were observed in the root of Rosa rugosa and the leaves of Prunus sargentii, at a concentration of 100 microg/mL. Rosamultin isolated from the root of R. rugosa inhibited HIV-1 protease by 53% at a concentration of 100 microM.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1 , Phytotherapy , Plant Extracts/therapeutic use , Rosa/chemistry , Triterpenes/therapeutic use , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , HIV Protease/drug effects , HIV Protease/metabolism , HIV Protease Inhibitors/pharmacology , HIV-1/enzymology , HIV-1/genetics , Humans , Plant Extracts/pharmacology , Treatment Outcome , Triterpenes/pharmacologyABSTRACT
Four known flavonoids and two galloyl glucoses isolated from the stem-bark of Juglans mandshurica (Juglandaceae), namely taxifolin (1), afzelin (2), quercitrin (3), myricitrin (4), 1,2,6-trigalloylglucose (5), and 1,2,3,6-tetragalloylglucose (6), were evaluated for their anti-complement activity against complement system. Afzelin (2) and quercitrin (3) showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) values of 258 and 440 microM. 1,2,6-Trigalloylglucose (5) and 1,2,3,6-tetragalloylglucose (6) exhibited anti-complement activity with IC(50) values of 136 and 34 microM. In terms of the evaluation of the structure-activity relationship of 3,5,7-trihydroxyflavone, compounds 2, 3, and 4 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (4a) as their aglycones, and these were also tested for their anti-complement activity. Of the three aglycones, kaempferol (2a) exhibited weak anti-complement activity with an IC(50) value of 730 microM, while quercetin (3a) and myricetin (4a) were inactive in this assay system. Among the compounds tested, 1,2,3,6-tetragalloylglucose (6) showed the most potent anticomplement activity (IC(50), 34 microM).
Subject(s)
Complement Inactivator Proteins/pharmacology , Complement System Proteins/metabolism , Juglans , Plant Bark , Plant Stems , Animals , Complement Inactivator Proteins/chemistry , Complement Inactivator Proteins/isolation & purification , Dose-Response Relationship, Drug , Humans , Male , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , SheepABSTRACT
For the purpose of discovering anti-HIV-1 agents from natural sources, water and EtOH extracts of 50 Thai plants were screened for their inhibitory activity against HIV-1 integrase (IN), an enzyme essential for viral replication. Of these plants, an EtOH extract of Coleus parvifolius Benth. (aerial parts) showed potent activity against HIV-1 IN with an IC50 value of 9.2 microg/mL. From this extract, 11 compounds were isolated and identified as luteolin 5-O-beta-d-glucopyranoside (1), luteolin (2), luteolin 7-methyl ether (3), luteolin 5-O-beta-d-glucuronide (4), 5-O-beta-d-glucopyranosyl-luteolin 7-methyl ether (5), rosmarinic acid (6), rosmarinic acid methyl ester (7), daucosterol (8), a mixture of alpha- and beta-amyrin (9, 10) and phytol (11). Of these compounds, rosmarinic acid methyl ester (7), rosmarinic acid (6), luteolin (2) and luteolin 7-methyl ether (3) exhibited inhibitory activities against HIV-1 IN with IC50 values of 3.1, 5.0, 11.0 and 11.0 microM, respectively. Among rosmarinic acid derivatives, the HIV-1 IN inhibitory activity increased in turn for a dimer (IC50 = 5.0 microM), a trimer (IC50 = 1.4 microM), and a tetramer (IC50 = 1.0 microM).
Subject(s)
Anti-HIV Agents/pharmacology , Coleus , HIV Integrase/drug effects , HIV-1/drug effects , Phytotherapy , Plant Extracts/pharmacology , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Flowers , Fruit , Humans , Medicine, Traditional , Microbial Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Plant Leaves , Plant Roots , Seeds , Thailand , Tumor Cells, Cultured/drug effectsABSTRACT
To identify substances with anti-human immunodeficiency virus (HIV) activity in traditional medicines, 101 extracts of Korean medicinal plants were screened for their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was determined by HPLC. Of the extracts tested, strong inhibitory effects were observed in the acetone extracts of the pericarp and leaves of Camellia japonica, the water extract of the leaves of Sageretia theezans and the methanol extract of the aerial part of Sophora flavescens. Camelliatannin H from the pericarp of C. japonica, showed a potent inhibitory activity on HIV-1 PR with IC(50) of 0.9 microM.
Subject(s)
Camellia/chemistry , HIV Protease Inhibitors/pharmacology , HIV Protease/metabolism , HIV-1/enzymology , Hydrolyzable Tannins , Plants, Medicinal/chemistry , Tannins/pharmacology , Chromatography, High Pressure Liquid , HIV Infections/drug therapy , HIV Infections/virology , HIV Protease Inhibitors/isolation & purification , HIV-1/drug effects , Korea , Molecular Structure , Phytotherapy , Plant Extracts/chemistry , Plant Structures/chemistry , Tannins/isolation & purificationABSTRACT
Water and methanol extracts of 30 Chinese and Mongolian medicinal plants were tested for their human immunodeficiency virus type-1 (HIV-1) inhibitory activity. Of the 60 extracts, 23 showed anti-HIV activity. Bioassay-guided fractionation of one of the most active extracts, the methanol extract of the root tuber of Stephania cepharantha, led to the isolation of two alkaloids, aromoline and FK-3000 as potent inhibitory substances. They completely inhibited the cytopathic effects of HIV-1 on MT-4 cells at 31.3 and 7.8 microg/mL, respectively.
Subject(s)
Alkaloids/pharmacology , Drugs, Chinese Herbal , HIV-1/drug effects , Isoquinolines/pharmacology , Alkaloids/chemistry , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Cell Line , China , Humans , Inhibitory Concentration 50 , Isoquinolines/chemistry , Mongolia , Plant Extracts/pharmacology , Plant Structures/chemistry , Plants, Medicinal/classification , Tumor Cells, CulturedABSTRACT
In an effort to develop new drugs preventing the growth of human immunodeficiency virus (HIV), we developed an in vitro assay method of ribonuclease H (RNase H) activity associated with reverse transcriptase (RT) from HIV-1. Some naphthoquinones, such as 1,4-naphthoquinone (1), vitamin K(3) (2), juglone (3) and plumbagin (6), moderately inhibited RNase H activity, and others, including naphthazarin (5) and shikonins (8-9, 18-23), showed weak inhibition. Diterpenoid quinones, tanshinones (24-28), had also moderate inhibition against RNase H activity. Of these quinones, compound 1 showed the most potent inhibition on RNase H activity with a 50% inhibitory concentration (IC(50)) of 9.5 microM, together with moderate inhibition against RNA-dependent and DNA-dependent DNA polymerase (RDDP and DDDP) activities with IC(50) values of 69 and 36 microM, respectively. Compounds 3 and 5 showed significant inhibition against RDDP (IC(50) = 8 and 10 microM, respectively) and DDDP (IC(50) = 5 and 7 microM, respectively) activities. The structure-activity relationship of the naphthoquinones suggested that non-hydroxylated naphthoquinones (1 and 2) showed significant inhibition of RNase H activity, whereas 5-hydroxylated naphthoquinones (3 and 5) showed potent inhibition against RDDP and DDDP activities.
