Synthesis, chemical characterization of novel 1,3-dimethyl acridones as cytotoxic agents, and their DNA-binding studies
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2010
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Abstract
A series of new 1,3-dimethyl acridone derivatives were synthesized with different alkyl side chain (propyl and butyl) substitution at N 10-position and highly basic amine groups at terminal end of alkyl side chain. All the synthesized molecules were screened for their cytotoxic activity against human breast adenocarcinoma (MCF-7) and human promyelocytic leukemia (HL-60) cell lines. DNA binding constants (K<inf>i</inf>) of selected compounds were determined with calf-thymus DNA. Results showed that the molecules 7, 8, 10, 11, 12, 13, 14, and 15 exhibited good cytotoxic activity with IC<inf>50</inf> value <10 ?M. Compound 14 having (?- hydroxyethyl) piperazine butyl side chain exhibited potent cytotoxic activity against MCF-7 cell line and DNA-intercalating properties. Examination of the relationship between lipophilicity and acridone derivatives showed poor correlation. © Birkhäuser Boston 2009.
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Keywords
1,3 dimethyl 10h acridinone, 10 (3 chloropropyl) 1,3 dimethyl 10h acridinone, 10 (3' n morpholinopropyl) 1,3 dimethyl 10h acridinone, 10 (3' n piperidinopropyl) 1,3 dimethyl 10h acridinone, 10 (3' n pyrrolidinopropyl) 1,3 dimethyl 10h acridinone, 10 (4' chlorobutyl) 1,3 dimethyl 10h acridinone, 10 (4' n [(beta hydroxyethyl)piperazine]butyl] 1,3 dimethyl 10h acridinone, 10 (4' n morpholinobutyl) 1,3 dimethyl 10h acridinone, 10 (4' n piperidinobutyl) 1,3 dimethyl 10h acridinone, 10 (4' n pyrrolidinobutyl) 1,3 dimethyl 10h acridinone, 10 [3' (n diethylamino)propyl] 1,3 dimethyl 10h acridinone, 10 [3' n (methylpiperazino)]propyl 1,3 dimethyl 10h acridinone, 10 [3' n [(beta hydroxyethyl)piperazine]propyl] 1,3 dimethyl 10h acridinone, 10 [4' (n diethylamine)butyl] 1,3 dimethyl 10h acridinone, 10 [4' n (methylpiperazino)butyl] 1,3 dimethyl 10h acridinone, acridone derivative, cyclophosphamide, cytotoxic agent, DNA, doxorubicin, unclassified drug, alkylation, antineoplastic activity, article, binding affinity, catalysis, cell strain HL 60, cell strain MCF 7, controlled study, cyclization, cytotoxicity, drug DNA binding, drug synthesis, human, human cell, hydrophobicity, IC 50, lipophilicity, substitution reaction
Citation
Medicinal Chemistry Research, 2010, 19, 7, pp. 674-689