Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields

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• 作者：Branko J. Drakulić ; Tatjana P. Stanojković ; &#x17d ; eljko S. &#x17d ; i&#x17e ; ak ; Milan M. Dabović
• 关键词：4-aryl-4-oxo-2-butenoic acids ; Antiproliferative activity ; Human tumors ; Molecular interaction fields
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：46
• 期：8
• 页码：3265-3273
• 全文大小：982 K

文摘

Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted.