Abstract
Novel thiazolo[5,4-b]quinoline derivatives were prepared with or without a (2-(azacycloalkyl)ethyl)amino substituent at the 2-position. The effect of the substituent at 2-position on cytotoxic activity, DNA-intercalation and cytotoxic properties were evaluated. Substituents at 2-position bearing an aliphatic amine favored cytotoxicity, while removal of these substituents resulted in low or negligible cytotoxic properties. Additionally, the in silico predicted binding mode of the novel compounds into DNA correlated with the experimental intercalation data. These results suggest a strong influence of the substituent at 2-position on the DNA intercalation properties.
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References
Baldwin JJ, Engelhardt EL, Hirschmann R, Ponticello GS, Atkinson JG, Wasson BK, Sweet CS, Scriabine A (1980) Heterocyclic analogues of the antihypertensive beta-adrenergic blocking agent (S)-2-[3-(ter-butylamino)-2-hydroxypropoxy]-3-cyanopyridine. J Med Chem 23:65–70
Bondarev DA, Skawinski WJ, Venanzi CA (2000) Nature of intercalator amiloride-nucelobase stacking. an empirical potential and ab initio electron correlation study. J Phys Chem B 104:815–822
Chen Y-L, Chen I-L, Lu C-M, Tzeng C-C, Tsao L-T, Wang J-P (2004) Synthesis and anti-inflammatory evaluation of 4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives. Bioorg Med Chem 12:387–392
Chen Y-L, Chen I-L, Wang T-C, Han C-H, Tzeng C-C (2005) Synthesis and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinoline and 4-anilinofuro[3,2-c]quinoline derivatives. Eur J Med Chem 40:928–934
Demecunynck H, Charmantray F, Martelli A (2001) Interest of acridine derivatives in the anticancer chemotherapy. Curr Pharm Des 7:1703–1724
Denny WA (1995) The role of intercalation and DNA binding in the activity of acridines and related tricyclic DNA-intercalating agents. In: Foye WO (ed) Cancer chemotherapeutic agents. ACS, Washington, pp 218–239
Denny WA (2002) Acridine derivatives as chemotherapeutic agents. Curr Med Chem 9:1655–1665
González-Sánchez I, Solano JD, Loza-Mejía MA, Olvera-Vázquez S, Rodríguez-Sotres R, Morán J, Lira-Rocha A, Cerbon M (2011) Antineoplastic activity of the thiazolo[5,4-b]quinoline derivative D3CLP in K-562 cells is mediated through effector caspases activation. Eur J Med Chem 46:2102–2108
Gunawardana GP, Kohmoto S, Gunasekera SP, McConnell OJ, Koehn FE (1988) Dercitin, a new biologically active acridine alkaloid from a deep water marine sponge, Dercitus sp. J Am Chem Soc 110:4856–4860
He Y, Ma X, Ji HF, Zha XB, Jiang H, Lu M (2012) Selective oxidation of sulfides to sulfoxides/sulfones by 30 % hydrogen peroxide. Phosphorus Sulfur Silicon Relat Elem 187:822–830
Herrera A, Martínez-Alvarez R, Ramiro P, Molero D, Almy J (2006) New easy approach to the synthesis of 2,5-disubstituted and 2,4,5-trisubstituted 1,3-oxazoles. The reaction of 1-(methylthio)acetone with nitriles . Org Chem 71:3026–3032
Hoelder S, Clarke PA, Workman P (2012) Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol 6:155–176
Kerdesky FA, Seif LS (1995) A novel and efficient synthesis of 5-(hydroxymethyl) thiazole: an important synthon for preparing biologically active compounds. Synth Commun 25:2639–2645
Lindsey RH, Pendleton M, Ashley RE, Mercer SL, Deweese JE, Osheroff N (2014) Catalytic core of human topoisomerase IIα: insights into enzyme-DNA interactions and drug mechanism. Biochemistry 53:6595–6602
Loza-Mejía MA, Maldonado-Hernández K, Rodríguez-Hernández F, Rodríguez-Sotres R, González-Sánchez I, Solano JD, Lira-Rocha A (2008) Synthesis, cytotoxic evaluation, and DNA binding of novel thiazolo[5,4-b]quinoline derivatives. Bioorg Med Chem 16:1142–1149
Loza-Mejía MA, Olvera-Vázquez S, Maldonado-Hernández K, Guadarrama-Salgado K, González-Sánchez I, Rodríguez-Hernández F, Solano JD, Rodríguez-Sotres R, Lira-Rocha A (2009) Synthesis, cytotoxic activity, DNA topoisomerase-II inhibition, molecular modeling and structure–activity relationship of 9-anilinothiazolo[5,4-b]quinoline derivatives. Bioorg Med Chem 17:3266–3277
Maia JDC, Carvalho GAU, Mangueira CP, Santana SR, Cabral LAF, Rocha GB (2012) GPU linear algebra libraries and GPGPU programming for accelerating MOPAC semiempirical quantum chemistry calculations. J Chem Theory Comput 8:3072–3081
Malinina L, Soler-López M, Aymamí J, Subirana JA (2002) Intercalation of an acridine-peptide drug in an AA/TT base step in the crystal structure of [d(CGCGAATTCGCG)](2) with six duplexes and seven Mg(2+) ions in the asymmetric unit. Biochemistry 41:9341–9348
Medhi C, Mitchell JBO, Price SL, Tabor AB (1999) Electrostatic factors in DNA intercalation. Biopolymers 52:84–93
McConnaughie WA, Jenkins TC (1995) Novel acridine-triazenes as prototype combilexins: synthesis, DNA binding, and biological activity. J Med Chem 38:3488–3501
Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662
Morris GM, Goodsell DS, Huey R, Olson AJ (1996) Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4. J Comput Aided Mol Des 10:293–304
Quintero A, Pelcastre A, Dolores J, Guzmán E, Díaz E (1999) Antitumoral activity of new pyrimidine derivatives of sesquiterpene lactones. J Pharm Pharm Sci 2:108–112
Rodríguez-Loaiza P, Quintero A, Rodríguez-Sotres R, Solano JD, Lira-Rocha A (2004) Synthesis and evaluation of 9-anilinothiazolo[5,4-b]quinoline derivatives as potential antitumorals. Eur J Med Chem 39:5–10
Sato K, Hyodo M, Aoki M, Zheng X-Q, Noyori R (2001) Oxidation of sulfides to sulfoxides and sulfones with 30 % hydrogen peroxide under organic solvent- and halogen-free conditions. Tetrahedron 57:2469–2476
Stewart JJP MOPAC (2012) Stewart Computational Chemistry, Version 15.140L web: http://OpenMopac.net
Siu F-M, Pommier Y (2013) Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors: a molecular dynamics study. Nucleic Acid Res 41:10010–10019
Vriend G (1990) WHAT IF: a molecular modeling and drug design program. J Mol Graph 8:52–56
Xiao X, Antony S, Pommier Y, Cushman M (2005) On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage complex. J Med Chem 48:3231–3238
Yin G, Wang Z, Chen A, Gao M, Wu A, Pan Y (2008) A new facile approach to the synthesis of 3-methylthio-substituted furans, pyrroles, thiophenes, and related derivatives. J Org Chem 73:3377–3383
Zumbrunn A (1998) The first versatile synthesis of 1-alkyl-3-fluoro-1H-[1,2,4]triazoles. Synthesis 9:1357–1361
Acknowledgments
We thank Maricela Gutiérrez, Rosa Isela del Villar, Victor M. Arroyo, Georgina Duarte and Margarita Guzmán for determination of all spectra. A.K.L.R. thanks DGAPA-UNAM for a scholarship. We also thank DGAPA-UNAM for financing project PAPIIT IN2128910 and PAPIIT IN221113, as well as Facultad de Química for financial support (PAIP 6390-10, 6290-09), and UNAM-DGTIC-SC16-1-IR-111.
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Reyes-Rangel, F.J., López-Rodríguez, A.K., Pastrana-Cancino, L.V. et al. Synthesis, cytotoxic activity, DNA binding and molecular docking studies of novel 9-anilinothiazolo[5,4-b]quinoline derivatives. Med Chem Res 25, 2976–2988 (2016). https://doi.org/10.1007/s00044-016-1718-4
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DOI: https://doi.org/10.1007/s00044-016-1718-4