Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators

[Image: see text] P-glycoprotein (Pgp), an ATP binding cassette (ABC) transporter, is an ATP-dependent efflux pump responsible for cancer multidrug resistance. As part of efforts to identify human Pgp (hPgp) inhibitors, we prepared a series of novel triazole-conjugated dihydropyrimidinones using a s...

Descripción completa

Detalles Bibliográficos
Autores principales: Bijani, Sabera, Shaikh, Faraz, Mirza, Sheefa, Weng In Siu, Shirley, Jain, Nayan, Rawal, Rakesh, Richards, Nigel G. J., Shah, Anamik, Radadiya, Ashish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118204/
https://www.ncbi.nlm.nih.gov/pubmed/35601326
http://dx.doi.org/10.1021/acsomega.1c05839
_version_ 1784710464491487232
author Bijani, Sabera
Shaikh, Faraz
Mirza, Sheefa
Weng In Siu, Shirley
Jain, Nayan
Rawal, Rakesh
Richards, Nigel G. J.
Shah, Anamik
Radadiya, Ashish
author_facet Bijani, Sabera
Shaikh, Faraz
Mirza, Sheefa
Weng In Siu, Shirley
Jain, Nayan
Rawal, Rakesh
Richards, Nigel G. J.
Shah, Anamik
Radadiya, Ashish
author_sort Bijani, Sabera
collection PubMed
description [Image: see text] P-glycoprotein (Pgp), an ATP binding cassette (ABC) transporter, is an ATP-dependent efflux pump responsible for cancer multidrug resistance. As part of efforts to identify human Pgp (hPgp) inhibitors, we prepared a series of novel triazole-conjugated dihydropyrimidinones using a synthetic approach that is well suited for obtaining compound libraries. Several of these dihydropyrimidinone derivatives modulate human P-glycoprotein (hPgp) activity with low micromolar EC(50) values. Molecular docking studies suggest that these compounds bind to the M-site of the transporter.
format Online
Article
Text
id pubmed-9118204
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-91182042022-05-20 Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators Bijani, Sabera Shaikh, Faraz Mirza, Sheefa Weng In Siu, Shirley Jain, Nayan Rawal, Rakesh Richards, Nigel G. J. Shah, Anamik Radadiya, Ashish ACS Omega [Image: see text] P-glycoprotein (Pgp), an ATP binding cassette (ABC) transporter, is an ATP-dependent efflux pump responsible for cancer multidrug resistance. As part of efforts to identify human Pgp (hPgp) inhibitors, we prepared a series of novel triazole-conjugated dihydropyrimidinones using a synthetic approach that is well suited for obtaining compound libraries. Several of these dihydropyrimidinone derivatives modulate human P-glycoprotein (hPgp) activity with low micromolar EC(50) values. Molecular docking studies suggest that these compounds bind to the M-site of the transporter. American Chemical Society 2022-05-02 /pmc/articles/PMC9118204/ /pubmed/35601326 http://dx.doi.org/10.1021/acsomega.1c05839 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Bijani, Sabera
Shaikh, Faraz
Mirza, Sheefa
Weng In Siu, Shirley
Jain, Nayan
Rawal, Rakesh
Richards, Nigel G. J.
Shah, Anamik
Radadiya, Ashish
Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title_full Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title_fullStr Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title_full_unstemmed Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title_short Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
title_sort novel dihydropyrimidinone derivatives as potential p-glycoprotein modulators
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118204/
https://www.ncbi.nlm.nih.gov/pubmed/35601326
http://dx.doi.org/10.1021/acsomega.1c05839
work_keys_str_mv AT bijanisabera noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT shaikhfaraz noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT mirzasheefa noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT wenginsiushirley noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT jainnayan noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT rawalrakesh noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT richardsnigelgj noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT shahanamik noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators
AT radadiyaashish noveldihydropyrimidinonederivativesaspotentialpglycoproteinmodulators

Ejemplares similares