Synthesis and biological evaluation of 6H-1-benzopyrano[4,3-b]quinolin-6-one derivatives as inhibitors of colon cancer cell growth
A convenient synthesis of 6H-1-benzopyrano[4,3-b]quinolin-6-one derivatives was reported using 4-chloro-2-oxo-2H-chromene-3-carbaldehyde with different aromatic amines using silica sulfuric acid. The compounds were tested for their anticancer activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231) cancer cells. These com-pounds showed more selectivity and potent cytotoxic activity against colon cancer cells. 3c was tested against five other colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), which had similar cytotoxicity and selectivity. 3c did not induce PXR-regulated ABCB1 or ABCG2 transporters. In fact, 3c induced cytotoxicity in HEK293 cells over expressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. It was cytotoxic approximately 3- and 5-fold to resistant colon carcinoma S1-MI-80 cells. 3c also produced concentration-dependent changes in HCT-116 colon cancer cells, in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation.
Ajdini N, Leci O, Tabakovic I, Tabakovic K. Chemistry of coumarin, phase-transfer catalysis in the C-alkylation of 4-arylaminocoumarins. Bull Soc Chim.1984; 49: 495-500.
Bairagi S, Bhosale A, Deodhar MN. Design, Synthesis and Evaluation of Schiffs Bases of 4-Chloro-3-coumarin aldehyde as Antimicrobial Agents. E-J Chem. 2009; 6: 759-62.
Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res.1987; 47: 936-42.
Geissman TA. The chemistry of flavonoid compounds. Oxford, Pergamon Press, 1962.
Harborne JB. The Flavonoids. The advances in research since 1980. London, Chapman and Hall, 1988a.
Harborne JB. The flavonoids, The advances in research since 1986. London, Chapman and Hall, 1988b.
Hegab MI, Abdel-Fattah A-SM, Yousef NM, Nour HF, Mostafa AM, Ellithey M. Synthesis, X-ray structure, and pharmacological activity of some 6,6-disubstituted chromeno[4,3-b]- and chromeno-[3,4-c]-quinolines. Arch Der Pharm. 2007; 340: 396-403.
Henkels KM, Turchi J. Cisplatin-induced apoptosis pro-ceeds by caspase-3-dependent and -independent path-ways in cisplatin-resistant and -sensitive human ovarian cancer cell lines. Cancer Res. 1999; 59: 3077-83.
Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 1994; 84: 1415-20.
Miri R, Motamedi R, Rezaei MR, Firuzi O, Javidnia A, Shafiee A. Design, synthesis and evaluation of cytotoxicity of novel chromeno[4,3-b]quinoline derivatives. Arch Der Pharm. 2011; 344: 111-18.
Robey RW, Medina-Perez WY, Nishiyama K, Lahusen T, Miyake K, Litman T, Senderowicz AM, Ross DD, Bates SE. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res. 2001; 7: 145-52.
Mulakayala N, Rambabu D, Rao RM, Chaitanya M, Kumar CS, Kalle AM, Krishna GR, Reddy CM, Rao MVB, Pal M. Ultrasound mediated catalyst free synthesis of 6H-1-benzopyrano [4, 3-b] quinolin-6-ones leading to novel quinoline derivatives: Their evaluation as potential anti-cancer agents Bioorg Med Chem. 2012; 20: 759-68.
Pondugula SR, Dong H, Chen T. Phosphorylation and protein-protein interactions in PXR-mediated CYP3A repression. Expert Opin Drug Metab Toxicol. 2009; 5: 861-73.
Pondugula SR, Mani S. Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response. Cancer Lett. 2013; 328: 1-9.
Perin N, Uzelac L, Piantanida I, Karminski-Zamola G, Kralj M, Hranjec M. Novel biologically active nitro and amino substituted benzimidazo[1,2-a]quinolines. Bioorg Med Chem. 2011; 19: 6329-39.
Rappa G, Shyam K, Lorico A, Fodstad O, Sartorelli AC. Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16). Oncol Res. 2000; 12: 113-19.
Tabakovic I, Grujic Z, Bejtovic Z. Electrochemical synthesis of heterocyclic compounds. XII. Anodic oxidation of catechol in the presence of nucleophiles. J Heterocycl Chem. 1983; 20: 635-38.
Tabakovic K, Tabakovic I, Ajdini N, Leci O. A novel transformation of 4-arylamino coumarins to 6 H-1-benzopyrano[4,3-b]quinolin-6-ones under vilsmeier-haack conditions. Synthesis 1987; 3: 308-11.
Thaisrivongs MN, Janakiraman KT, Chong PK, Tomich LA, Dolack SR,Turner JW, Strohbach JC, Lynn MM, Horng RR, Hinshaw KD. Structure-based design of novel HIV protease inhibitors: Sulfonamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent non-peptidic inhibitors. J Med Chem. 1996; 39: 2400-10.
Vu AT, Campbell AN, Harris HA. Unwalla RJ, Manas ES, Mewshaw RE. Structure-based design of novel HIV protease inhibitors: Sulfonamide-containing 4-hydroxy-coumarins and 4-hydroxy-2-pyrones as potent non-peptidic inhibitors. Bioorg Med Chem Lett. 2007; 17: 4053-56.
Wu CP, Woodcock H, Hladky SB, Barrand MA. cGMP (guanosine 3',5'-cyclic monophosphate) transport across human erythrocyte membranes. Biochem Pharmacol. 2005; 69: 1257-62.
Yang ED, Zhao YN, Zhang K, Mack P. Daphnetin, one of coumarin derivatives, is a protein kinase inhibitor. Biochem Biophys Res Commun. 1999; 260: 682-85.
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