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5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

Authors :
S. Henry
Robert Kiss
Antonio Evidente
Ramesh Dasari
Snezna Rogelj
Ria Kidner
Florence Lefranc
Véronique Mathieu
Liliya V. Frolova
Mary R. Reisenauer
Xiaojie Yu
Andrew Brenner
Alexander Pertsemlidis
Alexander V. Aksenov
Xiuye Ma
Igor V. Magedov
Alexander Kornienko
Jerry Pelletier
David Cavazos
Regina Cencic
Henry, Sean
Kidner, Ria
Reisenauer, Mary R
Magedov, Igor V
Kiss, Robert
Mathieu, Véronique
Lefranc, Florence
Dasari, Ramesh
Evidente, Antonio
Yu, Xiaojie
Ma, Xiuye
Pertsemlidis, Alexander
Cencic, Regina
Pelletier, Jerry
Cavazos, David A
Brenner, Andrew J
Aksenov, Alexander V
Rogelj, Snezna
Kornienko, Alexander
Frolova, Liliya V.
Source :
European journal of medicinal chemistry, 120
Publication Year :
2016

Abstract

Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published

Details

Language :
English
Database :
OpenAIRE
Journal :
European journal of medicinal chemistry, 120
Accession number :
edsair.doi.dedup.....7b3e3ad72a05755f6291272e48937e29