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Intercalation,Cytotoxicity,and Molecular Modeling of Acenaphtho[1,2-b]pyrrole Chromophores as a New Family of Antitumor Agents

Intercalation,Cytotoxicity,and Molecular Modeling of Acenaphtho[1,2-b]pyrrole Chromophores as a New Family of Antitumor Agents
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摘要 To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA were rex;ealed through absorption titration, SYBR Green-DNA melt curve, circular dichroism(CD), and docking studies. It was identified that some of the compounds could intercalate into DNA along their long axis parallel to the base-pair long axis, making right-handed B form DNA transform to A-like conformation. Their binding potency varied with the different steric hindrance. Their cytotoxicity(IC50) against MCF-7 cells was found to range between 1.3 to 40.9 umol/L by MTT assay. Interestingly, the IC50 values did not show any obvious correlation to their binding constants with DNA. The chromophore with a carboxyl group exhibited the most potency of intercalating DNA and could be the promising precursor for the future intercalator for DNA, while the bromide demonstrated the highest cytotoxic activity in this series of compounds. To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA were rex;ealed through absorption titration, SYBR Green-DNA melt curve, circular dichroism(CD), and docking studies. It was identified that some of the compounds could intercalate into DNA along their long axis parallel to the base-pair long axis, making right-handed B form DNA transform to A-like conformation. Their binding potency varied with the different steric hindrance. Their cytotoxicity(IC50) against MCF-7 cells was found to range between 1.3 to 40.9 umol/L by MTT assay. Interestingly, the IC50 values did not show any obvious correlation to their binding constants with DNA. The chromophore with a carboxyl group exhibited the most potency of intercalating DNA and could be the promising precursor for the future intercalator for DNA, while the bromide demonstrated the highest cytotoxic activity in this series of compounds.
出处 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2008年第4期449-453,共5页 高等学校化学研究(英文版)
基金 the National Natural Science Foundation of China(No.30772622)
关键词 INTERCALATION CYTOTOXICITY 8-Oxo-SH-acenaphtho[1 2-b]pyrrole-9-carboxylic acid esters Intercalation Cytotoxicity 8-Oxo-SH-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters
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