Abstract
A number of isoindolo[l ,2-b]quinazolines and some benzo[4,5]isoquinolino[l,2-b]quinazolines as structural modification analogues of the antitumor compound batracylin were synthesized and evaluated against HL-60 cell growth and in topoisomerase II-mediated DNA cleavage assays. Of the compounds studied, 10,12-dihydro-7,8-methy lenedioxyisoindolo[ 1,2-b] quinazolin-12(10H)-one (1d), 2-amino-10,12-dihydroisoindolo[l ,2-b]quinazolin- 12(10H)-one (1p), and 2-amino-7,8-methylenedioxy-10,12-dihydroisoindolo[l ,2-b]quinazolin-12(10H)-one (1ab) exhibited good inhibitory activities against HL-60 cell lines as well as induction of topo II-mediated DNA cleavage activities.
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REFERENCES
S. Gabriel. Reduktion von Acylderivaten des o-Nitrobenzylamins. Berichte deut. chem. Gesell. 45:713–725 (1912).
A. M. Downes and F. Lions. Application of the amidomethylation reaction to the synthesis of quinazolines. J. Am. Chem. Soc. 72:3053–3056 (1950).
T. Kametani, K. Nyu, T. Yamanaka, and S. Takano. A novel synthesis of quinazoline derivatives with triethyl phosphite. J. Heterocycl. Chem. 8:1071–1073 (1971).
V. Pestellini, M. Ghelardoni, C. Bianchini, and A. Liquori. Boll. Chim. Farm. 117:54–60 (1978).
L. I. Spiessens and M. J. O. Anteunis. NMR studies on imidines. I. An 1H and 13C NMR study of 10,12-dihydroisoindolo[1,2-b] quinazoline-12-one. Bull. Soc. Chim. Belg. 90:1167–1176 (1981).
M.-J. Kabbe. Heterocyclen aus Diaminen und Diacylverbindungen. Liebigs Ann. Chem. 398–404 (1978).
J. Plowman, K. D. Paull, G. Atassi, S. D. Harrison, D. J. Dykes, H. J. Kabbe, V. L. Narayanan, and O. C. Yoder. Preclinical antitumor activity of batracylin (NSC 320846). Invest. New Drugs 6:147–153 (1988).
P. Mucci-LoRusso, L. Polin, M.-C. Bissery, F. Valeriote, J. Plowman, G. D. Luk, and T. H. Corbett. Activity of batracylin (NSC-320846) against solid tumors of mice. Invest. New Drugs 7:295–306 (1989).
M. M. Ames, D. A. Mathiesen, and J. M. Reid. Differences in N-acetylation of the experimental antitumor agent batracylin in the mouse and the rat. Invest. New Drugs. 9:219–225 (1991).
J. Rosevear and J. F. K. Wilshire. A comparison of the reactions of some ethyl N-arylcarbamates with those of the corresponding acetanilides. II. Amidomethylation with N-hydroxymethylphthalimide. Aust. J. Chem. 43:339–353 (1990).
B. D. Halligan, K. A. Edward, and L. F. Liu. Purification and characterization of a type II DNA topoisomerase from bovine calf thymus. J. Biol. Chem. 260:2475–2482 (1985).
T. Maniatis, E. F. Fritsch, and J. Sambrook. Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1982, pp. 149–185.
L. F. Liu, T. C. Rowe, L. Yang, K. M. Tewey, and G. L. Chen. Cleavage of DNA by mammalian DNA topoisomerase II. J. Biol. Chem. 258:15365–15370 (1983).
K. M. Tewey, T. C. Rowe, L. Yang, B. D. Halligan, and L. F. Liu. Adriamycin-induced DNA damage medicated by mammalian DNA topoisomerase II. Science 226:466–468 (1984).
D. A. Scudiero, R. H. Shoemaker, K. D. Paull, A. Monks, S. Tierney, T. H. Notziger, M. J. Currens, D. Seniff, and M. R. Boyd. Cancer Res. 48:4827–4833 (1988).
T.-C. Chou and P. Talalay. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regulat. 22:27–55 (1984).
J. Chou and T.-C. Chou. Dose-Effect Analysis with Microcomputers: Quantitation of ED 50, LD 50, Synergism, Antagonism, Low Dose Risk, Receptor-Ligand Binding and Enzyme Kinetics, Biosoft, Cambridge, UK, 1987.
T. C. Rowe, K. M. Tewey, and L. F. Liu. Identification of the breakage and reunion subunit of T4 DNA topoisomerase. J. Biol. Chem. 259:9177–9181 (1984).
E. F. M. Stephenson. Heterocyclic nitrogen compounds. IV. Further condensations with aldehydric acids and diamines. J. Chem. Soc. 2354–2357 (1954).
Z. Jankowski, K. Clenik, and R. Stolarski. Synthesis and dyeing examinations of 7H,9H-quinazolino[3,2-b]benz[d,e]isoquinolin-7-one. J. Soc. Dyers Colour. 91:370–372 (1975).
T. J. Vietti, F. A. Valeriote, R. Kalish, and D. Coulter. Kinetics of Cytotoxicity of VM-26 and VP-16-213 on L1210 Leukemia and Hematopoietic Stem Cells. Cancer Treat. Rep. 62:1313–1320 (1978).
C. C. Cheng. Structural aspects of antineoplastic agents—A new approach. In G. P. Ellis and G. B. West (eds.), Progress in Medicinal Chemistry, Elsevier Science, B.V. Amsterdam, 1988, Vol. 25, pp. 35–83.
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Luo, Y., Ren, YF., Chou, TC. et al. A Structured–Activity Relationship Study of Batracylin Analogues. Pharm Res 10, 918–923 (1993). https://doi.org/10.1023/A:1018929815422
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DOI: https://doi.org/10.1023/A:1018929815422