title: 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells.
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.
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Henry
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
authors.forename: Ria
authors.initials: R
authors.lastname: Kidner
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Reisenauer
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Magedov
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine, CP205/1, Boulevard du Triomphe, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine, CP205/1, Boulevard du Triomphe, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Service de Neurochirurgie, Hôpital Erasme, ULB, 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dasari
authors.affiliation: Dipartimento di Scienze Chimiche, Universita' di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Evidente
authors.affiliation: Greehey Children's Cancer Research Institute, UT Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yu
authors.affiliation: Greehey Children's Cancer Research Institute, UT Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Xiuye
authors.initials: X
authors.lastname: Ma
authors.affiliation: Greehey Children's Cancer Research Institute, UT Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pertsemlidis
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
authors.forename: Regina
authors.initials: R
authors.lastname: Cencic
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Cavazos
authors.affiliation: Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brenner
authors.affiliation: Department of Chemistry, North Caucasus University, 1a Pushkin St., Stavropol 355009, Russian Federation.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Aksenov
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
authors.forename: Snezna
authors.initials: S
authors.lastname: Rogelj
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. Electronic address: a_k76@txstate.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
authors.affiliation: Departments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA. Electronic address: lfrolova@nmt.edu.
authors.forename: Liliya V
authors.initials: LV
authors.lastname: Frolova
mesh_terms: D000070378:Amaryllidaceae / Q000737:chemistry / Q000276:immunology; D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D010936:Plant Extracts; C528221:crinine
keywords: Apoptosis resistance; Glioblastoma; Haemanthamine; Lycorine; Multidrug resistance; Translation inhibition