Epoxylathyrane Derivatives as MDR-Selective Compounds for Disabling Multidrug Resistance in Cancer

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Ferreira Ricardo J. PhD 1980 ) > Epoxylathyrane Deri...

Details
MARC

Reis, Mariana AlvesUniv Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal. (author)

Epoxylathyrane Derivatives as MDR-Selective Compounds for Disabling Multidrug Resistance in Cancer

Article/chapterEnglish2020

Publisher, publication year, extent ...

2020-05-08
Frontiers Media SA,2020
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-415253
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-415253URI
https://doi.org/10.3389/fphar.2020.00599DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Background: Multidrug resistance (MDR) has been regarded as one of the major hurdles for the successful outcome of cancer chemotherapy. The collateral sensitivity (CS) effect is one the most auspicious anti-MDR strategies. Epoxylathyrane derivatives 1-16 were obtained by derivatization of the macrocyclic diterpene epoxyboetirane A (17), a lathyrane-type macrocyclic diterpene isolated from Euphorbia boetica. Some of these compounds were found to strongly modulate P-glycoprotein (P-gp/ABCB1) efflux.Purpose: The main goal was to develop lathyrane-type macrocyclic diterpenes with improved MDR-modifying activity, by targeting more than one anti-MDR mechanism.Study design/methods: In this study, the potential CS effect of compounds 1-16 was evaluated against gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29) human cancer cells and their drug-resistant counterparts, respectively selected against mitoxantrone (EPG85-257RNOV; EPP85-181RNOV; HT-RNOV) or daunorubicin (EPG85-257RDB; EPP85-181RDB; HT-RDB). The most promising compounds (8, 15, and 16) were investigated as apoptosis inducers, using the assays annexin V/PI and active caspase-3.Results: The compounds were more effective against the resistant gastric cell lines, being the CS effect more significant in EPG85-257RDB cells. Taking together the IC50 values and the CS effect, compounds 8, 15, and 16 exhibited the best results. Epoxyboetirane P (8), with the strongest MDR-selective antiproliferative activity against gastric carcinoma EPG85-257RDB cells (IC50 of 0.72 mu M), being 10-fold more active against this resistant subline than in sensitive gastric carcinoma cells. The CS effect elicited by compounds 15 and 16 appeared to be by inducing apoptosis via caspase-3 activation. Structure-activity relationships of the compounds were additionally obtained through regression models to clarify the structural determinants associated to the CS effect.Conclusions: This study reinforces the importance of lathyrane-type diterpenes as lead molecules for the research of MDR-modifying agents.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
multidrug resistance
collateral sensitivity
apoptosis
Euphorbia
macrocyclic diterpenes
lathyrane
regression models

Added entries (persons, corporate bodies, meetings, titles ...)

Matos, Ana M.Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal (author)
Duarte, NoéliaUniv Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal (author)
Ahmed, Omar BauomyUniv Hosp Charite, Inst Pathol, Berlin, Germany (author)
Ferreira, Ricardo J.,PhD,1980-Uppsala universitet,Molekylär biofysik,Science for Life Laboratory, SciLifeLab,Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal(Swepub:uu)ricfe589 (author)
Lage, HermannUniv Hosp Charite, Inst Pathol, Berlin, Germany (author)
Ferreira, Maria-José U.Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal (author)
Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal.Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal (creator_code:org_t)

Related titles

In:Frontiers in Pharmacology: Frontiers Media SA111663-9812

Internet link

Find in a library

Frontiers in Pharmacology (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Reis, Mariana Al ...; Matos, Ana M.; Duarte, Noélia; Ahmed, Omar Bauo ...; Ferreira, Ricard ...; Lage, Hermann; show more...; Ferreira, Maria- ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

Articles in the publication: Frontiers in Pha ...

By the university: Uppsala University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se