title: Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties.
abstract: A multicomponent reaction of indane-1,3-dione, an aldehyde and an amine-containing aromatic compound leading to the formation of indenopyridine-based heterocyclic medicinal scaffolds has been investigated. It was found that the yields significantly improve when oxygen gas is bubbled through the reaction mixture, facilitating the oxidation of the intermediate dihydropyridine-containing compounds to their aromatic counterparts. Investigation of the reaction scope revealed that formaldehyde, as well as various aliphatic, aromatic and heteroaromatic aldehydes, works well as the aldehyde component. In addition, substituted anilines and diverse aminoheterocycles can be utilized in this process as the amine-containing component. Preliminary biological evaluation of the synthesized library identified a pyrimidine-based polycycle, which rivals the anticancer drug etoposide in its toxicity and apoptosis inducing properties toward a human T-cell leukemia cell line.
authors.affiliation: Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801, USA.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Manpadi
authors.forename: Pavel Y
authors.initials: PY
authors.lastname: Uglinskii
authors.forename: Shiva K
authors.initials: SK
authors.lastname: Rastogi
authors.forename: Karen M
authors.initials: KM
authors.lastname: Cotter
authors.forename: Yin-Shan C
authors.initials: YS
authors.lastname: Wong
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Anderson
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Ortega
authors.forename: Severine
authors.initials: S
authors.lastname: Van Slambrouck
authors.forename: Wim F A
authors.initials: WF
authors.lastname: Steelant
authors.forename: Snezna
authors.initials: S
authors.lastname: Rogelj
authors.forename: Paul
authors.initials: P
authors.lastname: Tongwa
authors.forename: Mikhail Yu
authors.initials: MY
authors.lastname: Antipin
authors.forename: Igor V
authors.initials: IV
authors.lastname: Magedov
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines