Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties

Madhuri Manpadi; Pavel Y. Uglinskii; Shiva K. Rastogi; Karen M. Cotter; Yin-Shan C. Wong; Lisa A. Anderson; Amber J. Ortega; Severine Van slambrouck; Wim F. A. Steelant; Snezna Rogelj; Paul Tongwa; Mikhail Yu. Antipin; Igor V. Magedov; Alexander Kornienko

doi:10.1039/B713820B

Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties†‡

Madhuri Manpadi,^a Pavel Y. Uglinskii,^b Shiva K. Rastogi,^a Karen M. Cotter,^a Yin-Shan C. Wong,^a Lisa A. Anderson,^a Amber J. Ortega,^a Severine Van slambrouck,^a Wim F. A. Steelant,^a Snezna Rogelj,^c Paul Tongwa,^d Mikhail Yu. Antipin,^de Igor V. Magedov*^b and Alexander Kornienko*^a

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* Corresponding authors

^a Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico, USA
E-mail: akornien@nmt.edu
Fax: +1 505 8355364
Tel: +1 505 8355884

^b Department of Organic Chemistry, Timiryazev Agriculture Academy, Moscow, Russia
E-mail: ibs@timacad.ru

^c Department of Biology, New Mexico Institute of Mining and Technology, Socorro, New Mexico, USA

^d Department of Natural Sciences, New Mexico Highlands University, Las Vegas, New Mexico, USA

^e Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russia

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.

Organic & Biomolecular Chemistry

Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties†‡

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Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties

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