Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties.
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.
Manpadi
Madhuri
M
Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801, USA.
Uglinskii
Pavel Y
PY
Rastogi
Shiva K
SK
Cotter
Karen M
KM
Wong
Yin-Shan C
YS
Anderson
Lisa A
LA
Ortega
Amber J
AJ
Van Slambrouck
Severine
S
Steelant
Wim F A
WF
Rogelj
Snezna
S
Tongwa
Paul
P
Antipin
Mikhail Yu
MY
Magedov
Igor V
IV
Kornienko
Alexander
A
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*
D000970:Antineoplastic Agents; D011725:Pyridines