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

Biomolecules ◽  
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.

scholarly journals New Phosphorus Analogs of Bevirimat: Synthesis, Evaluation of Anti-HIV-1 Activity and Molecular Docking Study

2019 ◽  
Vol 20 (20) ◽  
pp. 5209 ◽  
Author(s):  
Elwira Chrobak ◽  
Krzysztof Marciniec ◽  
Aleksandra Dąbrowska ◽  
Paweł Pęcak ◽  
Ewa Bębenek ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Effect ◽  
Docking Study ◽  
Strong Interactions ◽  
Molecular Docking Study ◽  
Gag Protein ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

Since the beginning of the human immunodeficiency virus (HIV) epidemic, many groups of drugs characterized by diverse mechanisms of action have been developed, which can suppress HIV viremia. 3-O-(3′,3′-Dimethylsuccinyl) betulinic acid, known as bevirimat (BVM), was the first compound in the class of HIV maturation inhibitors. In the present work, phosphate and phosphonate derivatives of 3-carboxyacylbetulinic acid were synthesized and evaluated for anti-HIV-1 activity. In vitro studies showed that 30-diethylphosphonate analog of BVM (compound 14a) has comparable effects to BVM (half maximal inhibitory concentrations (IC50) equal to 0.02 μM and 0.03 μM, respectively) and is also more selective (selectivity indices: 3450 and 967, respectively). To investigate the possible mechanism of antiviral effect of 14a, molecular docking was carried out on the C-terminal domain (CTD) of HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1, which was described as a molecular target for maturation inhibitors. Compared with interactions between BVM and the protein, an increased number of strong interactions between ligand 14a and protein, generated by the phosphonate group, was observed.

Benzothiazol Clubbed Imidazol-4-ones as Anti-fungal, Anti-tubercular and Anti-HIV-1 Agents: Their Synthesis and Molecular Docking Study

2019 ◽  
Vol 16 (4) ◽  
pp. 382-391
Author(s):  
Navin B. Patel ◽  
Asif R. Shaikh ◽  
Vatsal M. Patel ◽  
Edgar E. Lara-Ramirez ◽  
Gildardo Rivera
Keyword(s):  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Spectral Studies ◽  
Molecular Docking Study ◽  
Broth Microdilution Method ◽  
Anti Hiv ◽  
Hiv 1

Background: The present work describes antimicrobial, antimycobacterium and anti HIV-1 evaluation of newly synthesized 5-(4-Substituted-benzylidene)-3-[4-(5-methyl-benzothiazol- 2-yl)-phenyl]-2-phenyl-3,5-dihydro-imidazol-4-one (4a-o). The docking studies were performed in order to predict the potential binding affinities. Objective: The major aim of this study is to develop the new class of bezylidine candidate clubbed with benzothiazole with less toxicity and improved potency as antimicrobial, antitubercular and anti HIV-1. Methods: The titled compounds were characterized by spectral studies (IR, 1H NMR, 13C NMR and Mass). In vitro antimycobacterium activity was carried out using Lowenstein-Jensen medium method and antimicrobial activity using the broth microdilution method. The anti HIV-1 reverse transcriptase activity was determined by the colorimetric MTT method and inhibition of virusinduced cytopathogenicity in MT-4 cells. Results: Compound 4i (50 µM) showed better antifungal activity against A. clavatus. Compound 4g (50 µM) with 95% inhibition demonstrated good activity against M. tuberculosis H37Rv. Compound 4k showed CC50 (50 µM) against MT-4 (CD4+ Human T-cells containing an integrated HTLV-1 genome) cells by 50%, while 16 µM concentration value EC50 from the HIV-1 induced cytopathogenicity. Molecular docking study suggested that 4k interacted with the target with binding energy by Vina score (-10.3 Kcal/mol). Conclusion: The preliminary in vitro evaluation results revealed that some of the compounds have promising antimicrobial activities as well as antitubercular potency. Among the various substituents on benzylidene, the nitro group was the most beneficial for improving the anti-HIV-1 activity. Docking result suggested that 4k compound could be acting as a non-competitive or weak inhibitor of Reverse Transcriptase (RT).

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

1996 ◽  
Vol 7 (6) ◽  
pp. 330-337 ◽  
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.

Anti-HIV-1 Integrase Activity and Molecular Docking Study of Compounds from Caesalpinia  sappan L.

2015 ◽  
Vol 29 (5) ◽  
pp. 724-729 ◽  
Author(s):  
Supinya Tewtrakul ◽  
Prapaporn Chaniad ◽  
Somsak Pianwanit ◽  
Chatchanok Karalai ◽  
Chanita Ponglimanont ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Caesalpinia Sappan ◽  
Anti Hiv ◽  
Hiv 1

Synthesis and Molecular Docking Study of Novel Chromeno-chromenones as Anti-HIV-1 NNRT Inhibitors

Synlett ◽  
2015 ◽  
Vol 26 (14) ◽  
pp. 1969-1972 ◽  
Author(s):  
Sudhakar Bhusare ◽  
Hanmant Kasralikar ◽  
Suresh Jadhavar
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Anti Hiv ◽  
Hiv 1

Haloalkyl Phosphate Derivatives of AZT as Inhibitors of HIV: Studies in the Phosphate Region

1994 ◽  
Vol 5 (3) ◽  
pp. 162-168 ◽  
Author(s):  
C. McGuigan ◽  
S. Turner ◽  
S. R. Nicholls ◽  
T. J. O'Connor ◽  
D. Kinchington
Keyword(s):  
Biological Activity ◽  
Alkyl Chain ◽  
Antiviral Action ◽  
Alkyl Phosphate ◽  
Free Nucleotides ◽  
Order Of Magnitude ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

Novel haloalkyl phosphate derivatives of the anti-HIV nucleoside analogue AZT were prepared by phosphorochloridate chemistry. These materials were designed to act as labile membrane-soluble prodrugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced and selective antiviral action, which varied greatly with the structure of the phosphate moiety. By comparison to simple dialkyl phosphates, which are inactive against HIV-1, the introduction of halogen atoms into the alkyl (phosphate) chains led to anti-HIV activity. Although halogen substitution in just one alkyl chain was sufficient for biological activity, substitution in the second alkyl chain further enhanced activity. Conversely, stabilization of the second chain, by conversion to a phosphonate, led to a reduction in activity. In one case, the diastereo-isomers resulting from mixed stereochemistry at the phosphate centre were separated, and found to differ in activity by one order of magnitude. Lastly, the bis(mono- and di-chloroethyl) phosphates were prepared and found to display moderate anti-HIV activity.

Synthesis, in vitro Antiproliferative and Anti-HIV Activity of New Derivatives of 2-Piperazino-1,3-benzo[d]thiazoles

2010 ◽  
Vol 65 (11) ◽  
pp. 1372-1380 ◽  
Author(s):  
Yaseen A. Al-Soud ◽  
Haitham H. Al-Sa’doni ◽  
Sadeekah O. W. Saber ◽  
Reem H. M. Al-Shaneek ◽  
Najim A. Al-Masoudi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Lymphoblastic Leukemia ◽  
Human Tumor ◽  
Large Panel ◽  
Further Development ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

A series of N-{2-oxo-2-[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]}-(het)arenecarboxamides 4a - l, sulfonamide derivatives 8a - i as well as benzothiazole-containing N1-(2-oxoethyl)-N1-arylthioureas 9a - c have been synthesized. Compounds 4a - l and 9a were evaluated, in vitro, for their antiproliferative activity against a large panel of human tumor-derived cell lines. Compounds 4l and 9a were the most potent analogs in this series, showing remarkable effects on human splenic B-lymphoblastoid cells (WIL-2NS) and human acute B-lymphoblastic leukemia (CCRF-SB) cell lines (4l: CC50 = 5.1 and 7.3 μM, respectively), and compound 5 against CCRF-SB cell lines with CC50 = 2.3 μM. These compounds are leading candidates for further development. Compounds 6 - 7a - i were screened as inhibitors against HIV-1 and HIV-2, and no activity has been witnessed.

Synthesis, and Some Properties of, Amphiphilic Dinucleoside Phosphate Derivatives of 3′-azido-2′,3′-dideoxythymidine (AZT)

1994 ◽  
Vol 5 (6) ◽  
pp. 387-394 ◽  
Author(s):  
H. Schott ◽  
M. P. Häussler ◽  
P. Gowland ◽  
D. H. Horber ◽  
R. A. Schwendener
Keyword(s):  
Lipid Membranes ◽  
Human Erythrocytes ◽  
Water Soluble ◽  
Lytic Activity ◽  
New Class ◽  
Liposomal Formulations ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

N4-hexadecyl-5′-0-(4-monomethoxytrityl)-2′-deoxycytidine-3′-hydrogenphosphate was reacted with 3′-azido-2′,3′-dideoxythymidine (AZT) according to the hydrogenphosphate method to yield N4-hexadecyl-2′-deoxycytidylyl-(3′-5)-3′-azido-2′,3′-dideoxythymidine. N4-palmitoyl-5′-O-(4-monomethoxytrityl)-2′-deoxycytidine-3′-(2-chlorophenyl)-phosphate was condensed to AZT using the triester method to give N4-palmitoyl-2′-deoxycytidylyl-(3′-5′)-3,-azido-2′,3′-dideoxythymidine. Both dinucleosidephosphates have amphiphilic properties and represent a new class of AZT derivatives in which the polar AZT-5′-monophosphate is masked with lipophilic deoxycytidine residues of variable stability. The AZT derivatives are water soluble, by forming micelles, and as a result of their amphiphilic nature, they can be incorporated into the lipid membranes of liposomes. In contrast to the micellar drug preparations, the liposomal formulations were shown to exert no lytic activity on human erythrocytes. Both AZT derivatives have anti HIV-1 activity in vitro.

scholarly journals Anti-HIV-1 integrase effect of compounds fromAglaia andamanicaleaves and molecular docking study with acute toxicity test in mice

2015 ◽  
Vol 54 (4) ◽  
pp. 654-659 ◽  
Author(s):  
Jindaporn Puripattanavong ◽  
Pattreeya Tungcharoen ◽  
Prapaporn Chaniad ◽  
Somsak Pianwanit ◽  
Supinya Tewtrakul
Keyword(s):  
Molecular Docking ◽  
Acute Toxicity ◽  
Toxicity Test ◽  
Docking Study ◽  
Acute Toxicity Test ◽  
Molecular Docking Study ◽  
Anti Hiv ◽  
Hiv 1

Thiated derivatives of 2′,3′-dideoxy-3′-fluorothymidine: Synthesis, in vitro anti-HIV-1 activity and interaction with recombinant drug resistant HIV-1 reverse transcriptase forms

2011 ◽  
Vol 92 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Agnieszka Miazga ◽  
François Hamy ◽  
Séverine Louvel ◽  
Thomas Klimkait ◽  
Zofia Pietrusiewicz ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1
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