Sökning: WFRF:(Reis Ricardo)
> (2020-2024) >
Epoxylathyrane Deri...
Epoxylathyrane Derivatives as MDR-Selective Compounds for Disabling Multidrug Resistance in Cancer
-
- Reis, Mariana Alves (författare)
- Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal.
-
- Matos, Ana M. (författare)
- Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal
-
- Duarte, Noélia (författare)
- Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal
-
visa fler...
-
- Ahmed, Omar Bauomy (författare)
- Univ Hosp Charite, Inst Pathol, Berlin, Germany
-
- Ferreira, Ricardo J., PhD, 1980- (författare)
- Uppsala universitet,Molekylär biofysik,Science for Life Laboratory, SciLifeLab,Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal
-
- Lage, Hermann (författare)
- Univ Hosp Charite, Inst Pathol, Berlin, Germany
-
- Ferreira, Maria-José U. (författare)
- Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal
-
visa färre...
-
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)
- 2020-05-08
- 2020
- Engelska.
-
Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
- Relaterad länk:
-
https://doi.org/10.3...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://www.frontier...
-
https://urn.kb.se/re...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- multidrug resistance
- collateral sensitivity
- apoptosis
- Euphorbia
- macrocyclic diterpenes
- lathyrane
- regression models
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas