title: Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. sbanerj5@uthsc.edu.
authors.forename: Souvik
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. jwang58@uthsc.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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. spfeffer@uthsc.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Pfeffer
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. dma6@uthsc.edu.
authors.forename: Dejian
authors.initials: D
authors.lastname: Ma
authors.affiliation: 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. lpfeffer@uthsc.edu.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pfeffer
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. spatil3@uthsc.edu.
authors.forename: Shivaputra A
authors.initials: SA
authors.lastname: Patil
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. wli@uthsc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis, TN 38163, USA. dmiller@uthsc.edu.
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008545:Melanoma / Q000188:drug therapy; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D011725:Pyridines; D054852:Small Molecule Libraries
keywords: anti-proliferative activity; chromene; chromenopyridine; glioma; melanoma