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To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.
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Twenty-one lignans including three new ones (1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1D and 2D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate (13) exhibited anti-HIV-1 activity with an IC value of 5.27 μmol·L and a selective index (SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A (3) and diphyllin (8) demonstrated inhibitory activity against HIV-1 with IC values of 4.95 (SI > 6.2) and 0.38 μmol·L (SI = 5.3), respectively.
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OBJECTIVE: To design and synthesize HIV-1 Vif inhibitor RN-18 derivatives and investigate their antiviral activities. METHODS: RN-18 was used as the lead compound, and optimizations were carried out on the two side chains and the middle benzene ring. The anti-HIV-1 activities of the target compounds were analyzed by p24 assay, and the cytotoxicities of compounds with better activities were tested with MTT method. RESULTS: Twenty-eight new derivatives were prepared, and their structures were characterized by MS and 1H-NMR. The activity test showed that the antiviral activities of seven compounds were obviously improved, and the activity of compound 26 was increased to be 11 times higher than that of RN-18, with an EC50 value of 21.8 μmol·L-1. CONCLUSION: Replacing the middle benzene ring of RN-18 with heterocycles generally improves the anti-HIV-1 activity, which provides the basis for further study.
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Objective To study the lignans chemical constituents from Diaphragma Juglandis Fructus and their activity of inhibiting HIV. Methods The constituents were isolated from Diaphragma Juglandis Fructus and purified by column chromatography, and the structures were identified by spectra analysis and chemical methods.The activity of anti-HIV-1 were detected by LEDGF/p75-IN proteins complex ELISA kit. Results Sixteen compounds were isolated from Diaphragma Juglandis Fructus and the structures were identified as (-)-syringaresinol (1), (+)-pinoresinol (2), (+)-(7R,7’R,7″S,7’’’S,8S,8’S,8″S,8’’’S)-4″,4’’’-dihydroxy-3,3’,3″,3’’’,5,5’- hexamethoxy-7,9’;7’,9-diepoxy-4,8″;4’,8’’’-bisoxy-8,8’-dineolignan-7″,7’’’,9″,9’’’-tetraol (3), 2,3-dihydroxy-1-(4’-hydroxy-3’-methoxy- phenyl)-propan-1-one (4), 3-hydroxy-1-(4’-hydroxy-3’-methoxyphenyl)-propan-1-one (5), 3’,4’-dimethoxyphenylpropanediol (6), (2S)-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (7), 3-hydroxy-1-(4’-hydroxy-3’,5’-dimethoxy phenyl)-propan-1-one (8), (1R,5R,6R)-6-{4’-O-[8″-(7″-(4″-hydroxy-3″-methoxyphenyl)) glyceol]-3’,5’-dimethoxyphenyl}-3,7-dioxabicyclo [3.3.0] octan-2-one (9), curcasinlignan B (10), evofolin-B (11), (7S,8R)-dihydrodehydrodiconiferyl alcohol (12), pinnatifidanin C I (13), (+)-(7S,8S)-4,1’-dihydroxy-3,3’,5’-trimethoxy-7,8,9-trinor-8,4’-oxyneolignan-7,9-diol (14), dysosmarol (15), and 1-(4’-hydroxy-3’-methoxyphenyl)-2- [4″-(3-hydroxypropyl)-2″,6″-dimethoxyphenoxy]-propane-1,3-diol (16). Conclusion All compounds are isolated from Diaphragma Juglandis Fructus for the first time. Compound 13 has the potential activity of inhibiting HIV-1.
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Objective To investigate the diterpenes from the stem bark of Euphorbia neriifolia L. and their anti-HIV-1 activity. Methods The chemical constituents were isolated and purified by column chromatography over silica gel, ODS, MCI CHP-20P, Sephadex LH-20, and preparative HPLC. Their structures were identified by the analysis of their physicochemical properties and the spectral data of NMR and MS. The anti-HIV-1 activity of the compounds was tested by cell detection models established by HIV-1 NL4-3 infected MT-4 cells. Results Nine compounds were isolated from the stem bark of the plant, namely 12α-acetoxy- 3β,7α-dihydroxy-8α-methoxyingol (1), 3β,8α,12α-triacetoxy-7α-benzoyloxyingol (2), 3β,8α,12α-triacetoxy-7α-tigloyloxyingol (3), ent-3-oxoatis-16α,17-acetonide (4), 13β-hydroxy-3,15-dioxoatis-16-ene (5), ent-3β,(13S)-dihydroxyatis-16-en-14-one (6), atis-16- en-14-oxo-3β,13(S)-diol (7), ent-(13S),18-dihydroxyatis-16-ene-3,14-dione (8), 4,13β-dihydroxy-14-oxo-3,4-secoatis-16-en-3-oic acid methyl ester (9). Conclusion Compound 1 is a new natural product. Compounds 2-4, and 6-8 are isolated from the plant for the first time. Furthermore, compound 4 exhibited moderate anti-HIV-1 activities, with EC50 values of 8.7 μg/mL (SI = 1.92).
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To evaluate the anti-HIV-1 activities of 5 benzophenones non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as DY1203, DY1204, DY1119, DY1208 and DY1209 in vitro, the cytotoxicity of 5 compounds were tested on C8166, MT-4, H9 and PBMC with the MTT assay. The anti-HIV-1 activities of compounds were evaluated on laboratory-adapted strain, drug-resistant strains and primary isolated strains by p24 antigen expression ELISA. The inhibition of HIV-1 recombinant reverse transcriptase activity was assessed by ELISA assay. Among 5 compounds, DY1203 and DY1204 showed low cytotoxicities with CC50 greater than 200 μg·mL-1. DY1119, DY1208 and DY1209 showed strong anti-HIV-1 activities against HIV-1IIIB, HIV-174V, HIV-1RF/V82F/184V, HIV-1NL4-3 gp41(36G) N42S, HIV-1KM018, HIV-1TC-1 and HIV-1Wan. However, NNRTIs drug-resistant strain HIV-1A17 showed different resistance to these compounds. The 5 compounds proved active against HIV-1 recombinant reverse transcriptase. DY1208 is expected to become a new lead compound for its high therapeutic index. The results can provide new information for HIV-1 drug research and promote the development of new HIV-1 drugs.
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Background & objectives: Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. Methods: Aqueous and 50 per cent ethanolic extracts were prepared from leaves and stems of banaba and were evaluated for cytotoxicity and anti-HIV activity using in vitro reporter gene based assays. Further, three compounds were isolated from the 50 per cent ethanolic extract of banaba leaves using silica gel column chromatography and characterization done by HPLC, NMR and MS analysis. To delineate the mode of action of the active compounds, reverse transcriptase assay and protease assay were performed using commercially available kits. Results: All the extracts showed a dose dependent inhibition of HIV-1-infection in TZM-bl and CEM-GFP cell lines with a maximum from the 50 per cent ethanolic extract from leaves (IC50 = 1 to 25 μg/ml). This observation was confirmed by the virus load (p24) estimation in infected CEM-GFP cells when treated with the extracts. Gallic acid showed an inhibition in reverse transcriptase whereas ellagic acid inhibited the HIV-1 protease activity. Interpretation & conclusions: The present study shows a novel anti-HIV activity of banaba. The active components responsible for anti-HIV activity were gallic acid and ellagic acid, through inhibition of reverse transcriptase and HIV protease, respectively and hence could be regarded as promising candidates for the development of topical anti-HIV-1 agents.
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OBJECTIVE: To investigate the HIV-1 integrase inhibitory activity of endophytic fungi from medicinal plant Aquilaria sinensis (Lour.) Gilg. METHODS: HIV-1 integrase inhibitory activity of the isolated endophytic fungi was determined by HIV-1 integrase strand transfer inhibitory activity assay, and the active metabolites of the endophytic fungi with the greatest potential were studied by activity tracking. RESULTS: Among 78 strains of endophytic fungi isolated from A. sinensis, nine strains (11.54%) showed strong inhibitory activity against HIV-1 integrase. Three compounds were obtained from the fermentation of strain HN-AS-8 which was identified to be Chaetomium globosum by HIV-1 integrase strand reaction. Compound 1 inhibited HIV-1 integrase with IC50 value of 35.4 μmol · L-1, and compounds 1 and 3 were for the first time isolated from Chaetomium sp. CONCLUSION: Potential anti-HIV-1 metabolites exist in the endophytic fungi from A. sinensis, which can be new resources for new anti-AIDS drugs.