Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Novel (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives: Selective inhibition of MV-4-11 biphenotypic B myelomonocytic leukemia cells’ growth is accompanied by reactive oxygen species overproduction and apoptosis.

Uproszczony widok
cris.lastimport.scopus2024-02-12T20:45:39Z
dc.abstract.enA series of optically pure (R)- and (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives was designed and synthesized as novel anthramycin analogues in a three-step, one-pot procedure, and tested for their antiproliferative activity on nine following cell lines: MV-4-11, UMUC-3, MDA-MB-231, MCF7, LoVo, HT-29, A-549, A2780 and BALB/3T3. The key structural features responsible for exhibition of cytotoxic effect were determined: the (S)-configuration of chiral center and the presence of hydrophobic 4-biphenyl substituent in the side chain. Introduction of bromine atom into the 8 position (8g) or substitution of dilactam ring with benzyl group (8m) further improved the activity and selectivity of investigated compounds. Among others, compound 8g exhibited selective cytotoxic effect against MV-4-11 (IC50 = 8.7 μM) and HT-29 (IC50 = 17.8 μM) cell lines, while 8m showed noticeable anticancer activity against MV-4-11 (IC50 = 10.8 μM) and LoVo (IC50 = 11.0 μM) cell lines. The cell cycle arrest in G1/S checkpoint and apoptosis associated with overproduction of reactive oxygen species was also observed for 8e and 8m.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBieszczad, Bartosz
dc.contributor.authorMroczkowska, Magdalena
dc.contributor.authorTrzybiński, Damian
dc.contributor.authorWoźniak, Krzysztof
dc.contributor.authorCzajkowska, Joanna
dc.contributor.authorPSURSKI, MATEUSZ
dc.contributor.authorWietrzyk, Joanna
dc.contributor.authorMieczkowski, Adam
dc.contributor.authorWilczek, Marcin
dc.contributor.authorBagiński, Maciej
dc.date.accessioned2024-01-25T13:52:37Z
dc.date.available2024-01-25T13:52:37Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number4
dc.description.volume28
dc.identifier.doi10.1016/J.BMCL.2018.01.034
dc.identifier.issn0960-894X
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/113967
dc.identifier.weblinkhttps://www.sciencedirect.com/science/article/pii/S0960894X18300441?via%3Dihub#ab010
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBioorganic and Medicinal Chemistry Letters
dc.relation.pages618-625
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enTricyclic benzodiazepines
dc.subject.enSelective inhibition
dc.subject.enBiphenotypic B myelomonocytic leukemia
dc.subject.enReactive oxygen species overproduction
dc.subject.enApoptosis
dc.subject.enAnticancer activity
dc.titleNovel (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives: Selective inhibition of MV-4-11 biphenotypic B myelomonocytic leukemia cells’ growth is accompanied by reactive oxygen species overproduction and apoptosis.
dc.typeJournalArticle
dspace.entity.typePublication