Sökning: WFRF:(Ferreira Ricardo J. PhD 1980 )
> (2021) >
Theoretical studies...
Theoretical studies on 1,4-dihydropyridine derivatives as P-glycoprotein allosteric inhibitors : insights on symmetry and stereochemistry
-
- Mollazadeh, Shirin (författare)
- Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Razavi Khorasan, Iran.;Mashhad Univ Med Sci, Biotechnol Res Ctr, Pharmaceut Technol Inst, Mashhad, Razavi Khorasan, Iran.
-
- Hadizadeh, Farzin (författare)
- Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Razavi Khorasan, Iran.;Mashhad Univ Med Sci, Biotechnol Res Ctr, Pharmaceut Technol Inst, Mashhad, Razavi Khorasan, Iran.
-
- Ferreira, Ricardo J., PhD, 1980- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi,Univ Lisbon, Fac Pharm, Res Inst Med iMedULisboa, Lisbon, Portugal.
-
Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Razavi Khorasan, Iran;Mashhad Univ Med Sci, Biotechnol Res Ctr, Pharmaceut Technol Inst, Mashhad, Razavi Khorasan, Iran. Science for Life Laboratory, SciLifeLab (creator_code:org_t)
- 2020-06-23
- 2021
- Engelska.
-
Ingår i: Journal of Biomolecular Structure and Dynamics. - : Taylor & Francis. - 0739-1102 .- 1538-0254. ; 39:13, s. 4752-4763
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- P-glycoprotein (P-gp) is a key efflux pump involved in cellular multidrug resistance (MDR), lowering the concentration of many anticancer drugs in tumor cells by pumping them into the extracellular milieu. While previous studies identified 1,4-dihydropyridines (DHP) as putative P-gp allosteric inhibitors, none reported the effect of stereochemistry on the ability of DHPs to bind P-gp. In the present study both symmetric (1) and asymmetric (2 R,S) DHPs were designed as P-gp inhibitors and, after biological evaluation, molecular docking and molecular dynamics simulation (MD) studies were performed to gain insights on how both scaffolds interact with P-gp. The results were thoroughly analyzed i) to evaluate the role of the different substituents and ii) to assess how stereochemistry may affect binding of DHPs to P-gp. Our results suggest that both the substitution pattern and stereochemistry may have a significant impact not only in drug binding but also on membrane permeation/accumulation, thus compromising in which site the DHPs may exert their effect as P-gp efflux inhibitors. Therefore, it is our conclusion that the stereochemistry cannot be neglected during the development of novel 1,4-dihydropyridine derivatives.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- 1
- 4-dihydropyridines
- efflux inhibitors
- docking
- molecular dynamics simulations
- P-glycoprotein
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas