New cyclopenta[a]naphthalene derivatives. Synthesis of 2-(carbamylmethyl)-8-hydroxy-3H-cyclopental[a]naphthalene as a possible deoxyribonucleic acid binding agent.
8-Methoxy-1-oxo-2,3-dihydro-1H-cyclopenta]a]naphthalene (4) was converted to the oxalyl derivative (7) by treatment with diethyl oxalate in the presence of sodium ethoxide. Compound 7 in the form of the sodium salt was alkylated with ethyl bromoacetate in DMF to 2-(carbethoxymethyl)-8-methoxy-1-oxo-2,3-dihydro-1H-cyclopenta[a]naphthalene (8). Treatment of 8 with methanolic ammonia yielded the corresponding amide (9). Dealkylation of 8 with 48% HBr and subsequent esterification gave compound 10. Ammonolysis of 10 led to the amide 11, which after reduction and subsequent dehydration of the reduced product afforded the desired compound, 2-(carbamylmethyl)-8-hydroxy-3H-cyclopenta[a]naphthalene (2). Compound 2 was found to be mildly growth inhibitory to L1210 and CCRF--CEM leukemic cells in culture. From thermal transition temperature studies, compound 2 was found to bind to calf thymus DNA and the poly(deoxyribonucleotides), e.g., poly(dG).poly(dC), poly(dG-dC), poly(dA).poly(dT), and poly(dA-dT).
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D007942:Leukemia, Experimental; D051379:Mice; D009284:Naphthols / Q000138:chemical synthesis* / Q000494:pharmacology; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D013696:Temperature; D013950:Thymus Gland / Q000378:metabolism
D009284:Naphthols; D011089:Polydeoxyribonucleotides; C024880:2-(carbamylmethyl)-8-hydroxy-3H-cyclopenta(a)naphthalene; D004247:DNA