Antiproliferative activity and QSAR studies of a series of new 4-aminomethylidene derivatives of some pyrazol-5-ones

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• 作者：Violeta Markovi&#x107 ; ^a ; Slavica Eri&#x107 ; ^b ; Tatjana Stanojkovi&#x107 ; ^c ; Nevenka Gligorijevi&#x107 ; ^c ; Sandra Aranđ ; elovi&#x107 ; ^c ; Nina Todorovi&#x107 ; ^d ; Snež ; ana Trifunovi&#x107 ; ^e ; Nedeljko Manojlovi&#x107 ; ^f ; Ratomir Jeli&#x107 ; ^f ; Milan D. Joksovi&#x107 ; ^a ; ^{mjoksovic@kg.ac.rs"" rel=""nofollow}
• 关键词：Pyrazolones ; Antiproliferative activity ; Breast cancer ; Angiogenesis ; QSAR studies
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 August 2011
• 年：2011
• 卷：21
• 期：15
• 页码：4416-4421
• 全文大小：690 K

文摘

Twenty five 4-aminomethylidene derivatives obtained from 3-phenyl-2-pyrazolin-5-one and 1,3-diphenyl-2-pyrazolin-5-one were synthesized and tested for their antiproliferative activity against human breast cancer MDA-MB-361 and MDA-MB-453 cell lines. The compounds derived from 1,3-diphenyl-2-pyrazolin-5-one exhibited the most remarkable activity in the treatment of both cell lines. In vitro antiproliferative activities were accompanied by an important apoptotic fraction of both cell lines; also, compounds inhibited key endothelial cell functions implicated in invasion and angiogenesis. QSAR methods were performed in order to analyze the influence of structural features of the compounds investigated on the antiproliferative potential on MDA-MB-361 and MDA-MB-453 cancer cells. One-parameter heuristic analysis was performed and different whole molecule and fragmental descriptors were considered for rationalization of mechanism of interaction of these compounds with active place of hypothetical target included in tumorigenesis.