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Start Over Author "Kaye PT" Journal bioorganic medicinal chemistry
5 results on '"Kaye PT"'

1. Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives.

Author

Adeyemi CM, Faridoon, Isaacs M, Mnkandhla D, Hoppe HC, Krause RW, and Kaye PT

Subjects
Aldose-Ketose Isomerases antagonists & inhibitors, Amides chemical synthesis, Amides toxicity, Antimalarials chemical synthesis, Antimalarials toxicity, Fosfomycin analogs & derivatives, Fosfomycin pharmacology, HeLa Cells, Humans, Organophosphonates chemical synthesis, Organophosphonates toxicity, Plasmodium falciparum drug effects, Structure-Activity Relationship, Amides pharmacology, Antimalarials pharmacology, Organophosphonates pharmacology
Abstract

A series of novel and readily accessible N-benzylated (N-arylcarbamoyl)alkylphosphonate esters and related compounds have been prepared as potential antimalarial agents. Bioassays reveal that some of these compounds exhibit promising activity against Plasmodium falciparum, and exhibit no significant growth inhibition of HeLa cells., (Copyright © 2016. Published by Elsevier Ltd.)

Published
2016
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2. Synthesis and evaluation of 3-hydroxy-3-phenylpropanoate ester–AZT conjugates as potential dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors.

Author

Manyeruke MH, Olomola TO, Majumder S, Abrahams S, Isaacs M, Mautsa N, Mosebi S, Mnkandhla D, Hewer R, Hoppe HC, Klein R, and Kaye PT

Subjects
Anti-HIV Agents, HIV Infections drug therapy, HIV Infections virology, HIV Integrase metabolism, HIV Integrase Inhibitors chemical synthesis, HIV Reverse Transcriptase antagonists & inhibitors, HIV Reverse Transcriptase metabolism, HIV-1 enzymology, HeLa Cells, Humans, Molecular Docking Simulation, Reverse Transcriptase Inhibitors chemical synthesis, Structure-Activity Relationship, Zidovudine chemical synthesis, HIV Integrase Inhibitors chemistry, HIV Integrase Inhibitors pharmacology, HIV-1 drug effects, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors pharmacology, Zidovudine chemistry, Zidovudine pharmacology
Abstract

Novel 3-hydroxy-3-phenylpropanoate ester-azidothymidine (AZT) conjugates have been prepared using Baylis-Hillman methodology, and their potential as dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors has been explored using enzyme inhibition and computer modelling techniques; their activity and HeLa cell toxicity have been compared with those of their cinnamate ester analogues.

Published
2015
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3. Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors.

Author

Bodill T, Conibear AC, Mutorwa MK, Goble JL, Blatch GL, Lobb KA, Klein R, and Kaye PT

Subjects
Aldose-Ketose Isomerases metabolism, Amides chemistry, Amides pharmacology, Binding Sites, Carbamates chemistry, Carbamates pharmacology, Enzyme Activation drug effects, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Protein Binding drug effects, Aldose-Ketose Isomerases antagonists & inhibitors, Aldose-Ketose Isomerases chemistry, Amides chemical synthesis, Carbamates chemical synthesis, Drug Design
Abstract

DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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4. Synthesis and evaluation of coumarin derivatives as potential dual-action HIV-1 protease and reverse transcriptase inhibitors.

Author

Olomola TO, Klein R, Mautsa N, Sayed Y, and Kaye PT

Subjects
Coumarins chemical synthesis, HIV Infections drug therapy, HIV Infections virology, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, HIV Reverse Transcriptase metabolism, HIV-1 drug effects, Humans, Models, Molecular, Reverse Transcriptase Inhibitors chemical synthesis, Zidovudine chemical synthesis, Zidovudine chemistry, Zidovudine pharmacology, Coumarins chemistry, Coumarins pharmacology, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors pharmacology, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 enzymology, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors pharmacology
Abstract

Baylis-Hillman-derived 3-(benzylaminomethyl)coumarins have been treated, sequentially, with chloroacetyl chloride and propargylamine to afford alkynylated coumarins as substrates for Click Chemistry reactions with azidothymidine (AZT) in the presence of a Cu(I) catalyst. The dual-action HIV-1 protease (PR) and reverse transcriptase (RT) inhibition potential of the resulting N-benzylated cycloaddition products, and a series of non-benzylated analogues, has been explored using saturation transfer difference (STD) NMR, computer modelling and enzyme inhibition techniques., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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5. Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors.

Author

Bodill T, Conibear AC, Blatch GL, Lobb KA, and Kaye PT

Subjects
Aldose-Ketose Isomerases metabolism, Antimalarials chemistry, Computer Simulation, Drug Design, Fosfomycin chemistry, Fosfomycin pharmacology, Furans chemistry, Furans pharmacology, Molecular Structure, Multienzyme Complexes metabolism, Organophosphonates chemistry, Organophosphonates pharmacology, Oxidoreductases metabolism, Protein Binding, Aldose-Ketose Isomerases antagonists & inhibitors, Antimalarials chemical synthesis, Antimalarials pharmacology, Fosfomycin analogs & derivatives, Furans chemical synthesis, Multienzyme Complexes antagonists & inhibitors, Organophosphonates chemical synthesis, Oxidoreductases antagonists & inhibitors
Abstract

The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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