Synthesis and cytotoxic activity of novel benzopyrano[3,2-c]chromene-6,8-dione derivatives
Tóm tắt
4-Hydroxycoumarins constitute the structural nucleus of many natural products, drugs, and pesticides. Promising biological properties in new families of synthetic coumarins were recently reported. Therefore, efficient synthesis of new benzopyrano[3,2-c]chromene-6,8-dione was undertaken and the structures of 15 compounds were confirmed by their IR, Mass, 1H-NMR, and C, H, N analysis. Then, the cytotoxic activities of these compounds were assessed on four different human cancer cell lines (Raji, HeLa, LS180, and MCF-7). The results showed that these compounds had weak-to-moderate antitumoral activities and their IC50 ranged from 49 to more than 100 μM. Among the compounds 9,10-dihydro-7-(3-methoxyphenyl)-7H,11H-benzopyrano[3,2-c]chromene-6,8-dione [4k] demonstrated the highest activity. Furthermore, conformational analysis revealed that ortho substituents were clearly different from meta and para substituents.
Tài liệu tham khảo
Bedair AH, El-Hady NA, El-Latif MSA, Fakery AH, El-Agrody AM (2000) Synthesis of some new pyrano[2, 3-d]pyrimidine, 2-substituted[1,2,4]triazolo[1,5-c]pyrimidine and pyrimido[1,6-b][1,2,4]triazine derivatives. Farmaco 55:708–714
Colotta V, Cecchi L, Melani F, Filacchioni G, Martini C, Giannaccini G, Lucacchini A (1990) Tricyclic heteroaromatic systems. [1]benzopyranopyrrol-4-ones and [1]benzopyrano-1,2,3-triazol-4-ones as benzodiazepine receptor ligands. Synthesis and structure-activity relationships. J Med Chem 33:2646–2651
Colotta V, Cecchi L, Melani F, Filacchioni G, Martini C, Gelli S, Lucacchini A (1991a) Tricyclic heteroaromatic systems. Synthesis of 1, 3 and 1, 2 disubstituted [1]benzopyrano[4, 3-b]pyrrol-4-ones and structure–activity relationships as benzodiazepine receptor ligands. Il Farmaco 46:1139–1154
Colotta V, Cecchi L, Melani F, Filacchioni G, Martini C, Gelli S, Lucacchini A (1991b) Tricyclic heteroaromatic systems: [1]benzopyrano-pyrazol-4-ones as benzodiazepine receptor ligands. J Pharm Sci 80:276–279
Cravottoo G, Nano GM, Palmisano G, Tagliapietra S (2001) An asymmetric approach to coumarin anticoagulants via hetero-Diels–Alder cycloaddition. Tetrahedron Asymmetr 12:707–709
Crow FW, Doholke WK, Farley KA, Hadden CE, Hahn DA, Kaluzny BD, Mallory CS, Martin GE, Smith RF, Thamann TJ (1999) Complete spectroscopic structural characterization of novobiocin, isonovobiocin, decarbamylnovobiocin, 2-(O-carbamyl)novobiocin, and novobiocin-2,3-carbonate. J Heterocycl Chem 36:365–370
Ermili A, Roma G, Buonamici M, Cuttica A, Galante M, Orsini G, Passerini N (1979) Psychopharmacological study with K 8409, a 1H-naphtho[2, 1-b]pyran 3-dialkylamino substituted derivative. Farmaco Ed Sci 34:535–544
Farag NA, El-Tayeb W (2010) Design, synthesis and docking studies of new furobenzopyranones and pyranobenzopyranones as photoreagent towards DNA and as antimicrobial agents. Eur J Med Chem 45:317–325
Feuer G (1974) The metabolism and biological actions of coumarins. Prog Med Chem 10:85–158
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery JA, Stratmann RE, Burant JC, Dapprich S, Millam JM, Daniels AD, Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J, Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, Ortiz JV, Baboul AG, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Gonzalez C, Challacombe M, Gill PMW, Johnson B, Chen W, Wong WM, Andres JL, Gonzalez C, Head–Gordon M, Replogle ES, Pople JA (1998) Gaussian 98, Revision A.7; Gaussian, Inc.: Pittsburgh, PA
Georgiadis MP, Couladouros EA, Delitheos AK (1992) Synthesis and antimicrobial properties of 2H-pyran-3(6H)-one derivatives and related compounds. J Phar Sci 81:1126–1131
Halland N, Velgoard T, Jørgensen KA (2003) Direct asymmetric Michael reactions of cyclic 1,3-dicarbonyl compounds and enamines catalyzed by chiral bisoxazoline-copper(II) complexes. J Org Chem 68:5067–5074
Hermodson MA, Barker WM, Link KP (1971) Studies on the 4-hydroxycoumarins. Synthesis of the metabolites and some other derivatives of warfarin. J Med Chem 14:167–169
Jabbar SA, Twentyman PR, Watson JV (1989) The MTT assay underestimates the growth inhibitory effects of interferons. Br J Cancer 60:523–528
Jin LW, Hua DH, Shie FS, Maezawa I, Sopher B, Martin GM (2002) Novel tricyclic pyrone compounds prevent intracellular APP C99-induced cell death. J Mol Neurosci 19:57–61
Kang SS, Kim HJ, Jin C, Lee YS (2009) Synthesis of tyrosinase inhibitory (4-oxo-4H-pyran-2-yl)acrylic acid ester derivatives. Bioorg Med Chem Lett 19:188–191
Kasaplar P, Yilmazer O, Cağir A (2009) 6-Bicycloaryl substituted (S)- and (R)-5,6-dihydro-2H-pyran-2-ones: asymmetric synthesis, and anti-proliferative properties. Bioorg Med Chem 17:311–318
Kesten SR, Heffner TG, Johnson SJ, Pgsley TA, Wright JL, Wise LD (1999) Design, synthesis, and evaluation of chromen-2-ones as potent and selective human dopamine D4 antagonists. J Med Chem 42:3718–3725
Mahajan DH, Pannecouque C, De Clercq E, Chikhalia KH (2009) Synthesis and studies of new 2-(coumarin-4-yloxy)-4,6-(substituted)-S-triazine derivatives as potential anti-HIV agents. Arch Pharm (Weinheim) 342:281–290
Matos MJ, Viña D, Picciau C, Orallo F, Santana L, Uriarte E (2009) Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors. Bioorg Med Chem Lett 19:5053–5055
Mehdipour AR, Javidnia K, Hemateenejad B, Amirghofran Z, Miri R (2007) Dihydropyridine derivatives to overcome atypical multidrug resistance: design, synthesis, QSAR studies, and evaluation of their cytotoxic and pharmacological activities. Chem Biol Drug Des 70:337–346
Miri R, Javidnia K, Hemmateenejad B, Azarpira A, Amirghofran Z (2004) Synthesis, cytotoxicity, QSAR, and intercalation study of new diindenopyridine derivatives. Bioorg Med Chem 12:2529–2536
Miri R, Javidnia K, Sarkarzadeh H, Hemmateenejad B (2006) Synthesis, study of 3D structures, and pharmacological activities of lipophilic nitroimidazolyl-1,4-dihydropyridines as calcium channel antagonist. Bioorg Med Chem 14:4842–4849
Obaseki AO, Porter WR (1982) 4-Hydroxycoumarin/2-hydroxychromone tautomerism: infrared spectra of 2–13C and 3-D labeled 4-hydroxycoumarin and its anion. J Heterocycl Chem 19:385–390
Robinson A, Liu HY, Feaster J (1996) The first practical asymmetric synthesis of R and S-Warfarin. Tetrahedron Lett 37:8321–8324
Sagar R, Singh P, Kumar R, Maulik PR, Shaw AK (2005) Diastereoselective annulation of 4-hydroxypyran-2H-ones with enantiopure 2,3-dideoxy-alpha, beta-unsaturated sugar aldehydes derived from respective glycals. Carbohydrate Res 340:1287–1300
Stanchev S, Momekov G, Jensen F, Manolov I (2008) Synthesis, computational study and cytotoxic activity of new 4-hydroxycoumarin derivatives. Eur J Med Chem 43:694–706
Su CR, Yeh SF, Liu CM, Damu AG, Kuo TH, Chiang PC, Bastow KF, Lee KH, Wu TS (2009) Anti-HBV and cytotoxic activities of pyranocoumarin derivatives. Bioorg Med Chem 17:6137–6143
Tallarida RJ, Murray RP (1986) Manual of pharmacologic calculations with computer programs. Springer, New York
Trivedi KN, Madhava Rao SS, Mistry SV, Desai SM (2001) Chemistry of 4-hydroxycoumarin. J Ind Chem Soc 78:579–595