Anti-HIV Diterpenes from Coleus forskohlii¶

Various extracts of the aerial parts of Coleus forskohlii (Labiatae) were prepared and evaluated at their non cytotoxic concentration against HIV-1 NL4-3. Chloroform, ethyl acetate and n-butanol extracts showed 45.6, 66.5 and 37.7% inhibition of HIV, respectively in CEM-GFP cells infected with HIV-1NL4-3 at 5 μg/mL. Four diterpenes, 1-deoxyforskolin, 1,9-dideoxyforskolin, forskolin and isoforskolin were isolated from the chloroform extract and tested against the virus. Six semi-synthetic derivatives of forskolin have been prepared to study SAR. 1-Deoxyforskolin and forskolin were found to be active against HIVNL4-3. This is first report of anti HIV activity of this plant and its isolated constituents.

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Anti-HIV Activity of Alkaloids from Dasymaschalon echinatum

Natural Product Communications ◽

10.1177/1934578x1801300110 ◽

2018 ◽

Vol 13 (1) ◽

pp. 1934578X1801300 ◽

Cited By ~ 1

Author(s):

Samreang Bunteang ◽

Waraporn Chanakul ◽

Sakchai Hongthong ◽

Chutima Kuhakarn ◽

Watcharra Chintakovid ◽

...

Keyword(s):

Reverse Transcriptase ◽

Inhibitory Activity ◽

First Report ◽

Aerial Parts ◽

Amide Derivatives ◽

Bioassay Guided Fractionation ◽

First Time ◽

Anti Hiv ◽

Hiv 1

Bioassay-guided fractionation of the aerial parts of Dasymaschalon echinatum led to the isolation of five known aristolactams; aristolactam AII (1), aristolactam BII (2), piperolactam A (3), piperolactam C (4), and goniopedaline (5), together with two aphorphine alkaloids; duguevalline (6) and noraristolodione (7) and two amide derivatives; asperphenamate (8), and N -benzoyl-L-phenylalaninol (9). Alkaloids 2 and 7 were isolated for the first time from the Dasymaschalon genus. The anti-HIV 1 reverse transcriptase (RT) activity of all isolated compounds was determined. Except for aristolactam BII (2), this is the first report of the anti-HIV 1-RT activity of compounds 1 and 3-9. Compounds 1, 3, 5, 6 and 8 showed weak anti-HIV 1-RT inhibitory activity with IC50 ranging from 112.74 to 225.55μM.

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Fullerene Derivatives of Nucleoside HIV Reverse Transcriptase Inhibitors—In Silico Activity Prediction

International Journal of Molecular Sciences ◽

10.3390/ijms19103231 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3231 ◽

Cited By ~ 2

Author(s):

Aleksandra Dąbrowska ◽

Tomasz Pieńko ◽

Przemysław Taciak ◽

Katarzyna Wiktorska ◽

Zdzisław Chilmonczyk ◽

...

Keyword(s):

Reverse Transcriptase ◽

Hiv Reverse Transcriptase ◽

Reverse Transcriptase Inhibitors ◽

Activity Prediction ◽

Hiv Therapy ◽

C20 Fullerene ◽

Derivatives Of ◽

Anti Hiv ◽

Similar Affinity ◽

Hiv 1

Here we present new derivatives of nucleoside reverse transcriptase inhibitors with a C20 fullerene. The computational chemistry methods used in this study evaluate affinity of designed compounds towards the HIV-1 reverse transcriptase (RT) binding site and select the most active ones. The best of the designed compounds have superior or similar affinity to RT active site in comparison to most active test compounds, including drugs used in anti-HIV therapy.

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Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors

Acta Naturae ◽

10.32607/20758251-2013-5-1-63-72 ◽

2013 ◽

Vol 5 (1) ◽

pp. 63-72 ◽

Cited By ~ 18

Author(s):

S. P. Korolev ◽

O. V. Kondrashina ◽

D. S. Druzhilovsky ◽

A. M. Starosotnikov ◽

M. D. Dutov ◽

...

Keyword(s):

Integrase Inhibitor ◽

Integrase Inhibitors ◽

Mechanism Of Inhibition ◽

Immunodeficiency Virus ◽

Pharmacokinetic Properties ◽

Nitro Derivatives ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

Human immunodeficiency virus type 1 integrase is one of the most attractive targets for the development of anti-HIV-1 inhibitors. The capacity of a series of 2,1,3-benzoxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) selected using the PASS software to inhibit the catalytic activity of HIV-1 integrase was studied in the present work. Only the nitro-derivatives of these compounds were found to display inhibitory activity. The study of the mechanism of inhibition by nitro-benzofurazans/benzofuroxans showed that they impede the substrate DNA binding at the integrase active site. These inhibitors were also active against integrase mutants resistant to raltegravir, which is the first HIV-1 integrase inhibitor approved for clinical use. The comparison of computer-aided estimations of the pharmacodynamic and pharmacokinetic properties of the compounds studied and raltegravir led us to conclude that these compounds show promise and need to be further studied as potential HIV-1 integrase inhibitors.

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Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study

Biomolecules ◽

10.3390/biom10081148 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1148

Author(s):

Krzysztof Marciniec ◽

Elwira Chrobak ◽

Aleksandra Dąbrowska ◽

Ewa Bębenek ◽

Monika Kadela-Tomanek ◽

...

Keyword(s):

Molecular Docking ◽

Betulinic Acid ◽

Strong Interactions ◽

Molecular Docking Study ◽

Gag Protein ◽

Terminal Domain ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC50 (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest.

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Syntheses of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 2-substituted-5-fluoroaniline: "cytosine replacement" analogs of deoxycytidine for evaluation as anticancer and antihuman immunodeficiency virus (anti-HIV) agents

Canadian Journal of Chemistry ◽

10.1139/v00-105 ◽

2000 ◽

Vol 78 (8) ◽

pp. 1081-1088

Author(s):

Zhi-Xian Wang ◽

Leonard I Wiebe ◽

Erik De Clercq ◽

Jan Balzarini ◽

Edward E Knaus

Keyword(s):

Anticancer Agent ◽

Coupling Reaction ◽

Tumor Cell Lines ◽

Immunodeficiency Virus ◽

Sugar Ring ◽

Type Coupling ◽

Anti Hiv Agents ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

A group of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 5-fluoroaniline possessing a variety of aryl C-2 substituents (6a R = H, 6b R = F, 6c R = Me) were synthesized. Accordingly, a Heck-type coupling reaction of the 4-iodoaniline derivatives (13ac) with the bis(tert-butyldimethylsilyl)glycal (11) in the presence of Pd(OAc)2 and Ph3As, followed by removal of the tert-butyldimethylsilyl protection groups using n-Bu4N+F-, yielded the corresponding 4-(β-D-glycero-pentofuran-3-ulos-1-yl)aniline derivatives (14ac) having a C-3 C=O in the sugar ring. Reduction of the C-3 C=O compounds (14ac) using NaB(OAc)3H afforded the target 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of the respective 2-substituted-5-fluoroaniline (6ac). The deoxycytidine mimic, 3-fluoro-4-[1-(2-deoxy-β-D-ribofuranosyl)]aniline (6a), in which the cytosine ring of deoxycytidine is replaced by a 4-(3-fluoroaniline) ring system, was inactive as an anticancer agent against a variety of tumor cell lines, and as an antihuman immunodeficiency virus (HIV-1, HIV-2) agent. The failure of this unnatural deoxycytidine mimic (6a) to exhibit anticancer-antiviral activity may be due to its inability to undergo phosphorylation by host cell- and virus-induced kinases.Key words: fluoroanilines, deoxycytidine mimics, anticancer-antihuman immunodeficiency virus (HIV) evaluation.

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Synthesis and Evaluation of Some Symmetrical Phosphate Dimer Derivatives of 3′-Modified Nucleosides as Potential anti-HIV Agents

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029600700606 ◽

1996 ◽

Vol 7 (6) ◽

pp. 330-337 ◽

Cited By ~ 2

Author(s):

C. McGuigan ◽

H.-W. Tsang ◽

N. Mahmood ◽

A. J. Hay

Keyword(s):

Human Immunodeficiency Virus ◽

Analytical Data ◽

Modified Nucleosides ◽

Nucleoside Analogues ◽

Immunodeficiency Virus ◽

Anti Hiv Agents ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

Novel symmetrical nucIeotide-(5′,5′)-dimers of 3′-O-acetylthymidine, 3′-O-methylthymidine, 3′-O-ethylthymidine, 3′-O-n-propylthymidine and 3′-azido-3′-deoxythymidine (AZT) were synthesized as membrane soluble pro-drugs. These were prepared using phosphorodichloridate chemistry and were characterised by spectroscopic and analytical data. In-vitro evaluation of the derivatives in cells acutely infected with the human immunodeficiency virus (HIV-1) demonstrated a range of activities. These derivatives were generally found to display poor inhibition of HIV proliferation. Derivatives containing AZT moieties were found to be potent, but such compounds were less active than the parent nucleoside. The data indicated that the AZT-containing compounds act primarily via the release of the free nucleoside. However, in some cases, the dimers of certain inactive nucleoside analogues were found to be active. In these cases, release of the nucleoside alone cannot account for the activity.

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Anti-HIV-1 Activities of Aerial Parts of Ocimum basilicum and its Parasite Cuscuta campestris

Journal of Antivirals & Antiretrovirals ◽

10.4172/jaa.1000064 ◽

2013 ◽

Vol 05 (03) ◽

Cited By ~ 3

Author(s):

Mandana Behbahani ◽

Hassan Mohabatkar ◽

Mohammad Soltani

Keyword(s):

Ocimum Basilicum ◽

Aerial Parts ◽

Cuscuta Campestris ◽

Anti Hiv ◽

Hiv 1

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New chalcones and thiopyrimidine analogues derived from mefenamic acid: microwave-assisted synthesis, anti-HIV activity and cytotoxicity as antileukemic agents

Zeitschrift für Naturforschung B ◽

10.1515/znb-2016-0223 ◽

2017 ◽

Vol 72 (4) ◽

pp. 249-256 ◽

Cited By ~ 2

Author(s):

Hanan A. Al-Hazam ◽

Zeki A. Al-Shamkani ◽

Najim A. Al-Masoudi ◽

Bahjat A. Saeed ◽

Christophe Pannecouque

Keyword(s):

Mefenamic Acid ◽

Leukemia Cells ◽

Basic Medium ◽

Microwave Assisted Synthesis ◽

Schmidt Reaction ◽

Microwave Assisted ◽

Amide Derivatives ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

AbstractThe development of new HIV non-nucleoside reverse transcriptase inhibitors offers the possibility of generating structures of increased potency. To this end, coupling of mefenamic acid (4) with 4-amino-acetophenone (6) in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine (DMAP) reagents afforded 4-(acetyphenyl)-2-((2,3-dimethylphenyl)amino)benzamide (7). Analogously, treatment of mefenamyl chloride (5) prepared from 4 with 6 under microwave irradiation (MWI) afforded 7. A new series of substituted chalconyl-incorporated amide derivatives of mefenamic acid 8–13 were synthesized from condensation of 7 with various substituted benzaldehydes via the Claisen–Schmidt reaction. Treatment of 8 and 11 with thiourea in a basic medium afforded the thiopyrimidine analogues 14 and 15, respectively. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 9 and 11 showed cytotoxicity values of 2.17 and 2.06 μm, respectively, against mock-infected MT-4 cells (C type adult T leukemia cells), which considered to be promising antileukemic agents.

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Synthesis and anti-HIV Activity of New Benzimidazole, Benzothiazole and Carbohyrazide Derivatives of the anti-Inflammatory Drug Indomethacin

Zeitschrift für Naturforschung B ◽

10.1515/znb-2011-0914 ◽

2011 ◽

Vol 66 (9) ◽

pp. 953-960 ◽

Cited By ~ 2

Author(s):

Najim A. Al-Masoudi ◽

Nadhir N. A. Jafar ◽

Layla J. Abbas ◽

Sadiq J. Baqir ◽

Christophe Pannecouque

Keyword(s):

Phenyl Isothiocyanate ◽

Reverse Transcriptase Inhibitors ◽

Inflammatory Drug ◽

Oxadiazole Derivatives ◽

Anti Inflammatory ◽

New Compounds ◽

Further Development ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

There is an urgent need for the design and development of new and safer drugs for the treatment of HIV infection, active against the currently resistant viral strains. New derivatives of the non-steroidal anti-inflammatory drug indomethacin bearing benzimidazoles, benzothiazole, purine and pyridine residues 8 - 13 were synthesized with the aim of developing new non-nucleoside reverse transcriptase inhibitors (NNRTIs).Alternatively, new imine analogs 16 - 20 were synthesized from condensation of indomethacinyl hydrazide 15, prepared from the ester 14, with various ketone precursors. Treatment of 15 with phenyl isothiocyanate or triethyl orthoformate afforded the phenylcarbonothioyl and the oxadiazole derivatives 21 and 22, respectively. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 9 and 10 were the most active in inhibiting HIV-2 and HIV-1, respectively, with EC50 ≥ 17.60 μgmL−1 and > 1.15 μgmL−1 (therapeutic indexes (SI) of ≥ 3 and < 1, respectively), and are leading candidates for further development.

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