Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents

• Main Authors: Souvik Banerjee, Jin Wang, Susan Pfeffer, Dejian Ma, Lawrence M. Pfeffer, Shivaputra A. Patil, Wei Li, Duane D. Miller
• Format: Article
• Language: English
• Published: MDPI AG 2015-09-01
• Series: Molecules
• Subjects: glioma; melanoma; chromene; chromenopyridine; anti-proliferative activity
• Online Access: http://www.mdpi.com/1420-3049/20/9/17152

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.