Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents
Souvik Banerjee,
Jin Wang,
Susan Pfeffer,
Dejian Ma,
Lawrence M. Pfeffer,
Shivaputra A. Patil,
Wei Li,
Duane D. Miller
Affiliations
Souvik Banerjee
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
Jin Wang
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
Susan Pfeffer
Department of Pathology and Laboratory Medicine, College of Medicine and the Center for Cancer Research, University of Tennessee Health Science Center, 19 S Manassas, Memphis, TN 38163, USA
Dejian Ma
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
Lawrence M. Pfeffer
Department of Pathology and Laboratory Medicine, College of Medicine and the Center for Cancer Research, University of Tennessee Health Science Center, 19 S Manassas, Memphis, TN 38163, USA
Shivaputra A. Patil
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
Wei Li
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
Duane D. Miller
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA
A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5H-chromenopyridine analogs to evaluate the impact of an additional ring, as well as conformational flexibility on cytotoxic activity against human melanoma and glioma cell lines. All of the 5H-thiochromenopyridines have been achieved in good yields (89%–93%) using a single-step, three-component cyclization without the need for purification. The 5H-chromenopyridine analog of the potent 5H-thiochromenopyride was obtained in a good yield upon purification. All newly-prepared 5H-thiochromenopyridines showed good to moderate cytotoxicity against three melanoma and two glioma cell lines (3–15 μM). However, the 5H-chromenopyridine analogue that we prepared in our laboratory lost cytotoxic activity. The moderate cytotoxic activity of 5H-thiochromenopyridines shows the promise of developing chromenopyridines as potential anticancer agents.
