title: Synthesis, characterization and Akt phosphorylation inhibitory activity of cyclopentanecarboxylate-substituted alkylphosphocholines.
abstract: Akt is activated in most human cancers and contributes to cell growth, proliferation and cellular survival pathway. Accordingly, it is an attractive target for anticancer therapy. A series of novel alkylphosphocholines, incorporating cyclopentanecarboxylate in the phospholipid head group with trans and cis orientations, were synthesized and evaluated for their Akt phosphorylation inhibitory activities and cytotoxicities against human cancer cell lines, A549, MCF-7 and KATO III. Among the synthesized compounds, 5a, 5b and 6c exhibited potent inhibitory Akt phosphorylation effects with IC50 value of 3.1, 2.0 and 3.0 μM, respectively, and their potencies were better than those of three reference compounds miltefosine, perifosine and edelfosine. All the new compounds, except 5d and 6e, displayed more potent growth inhibition against A549 cells than reference compounds. Specifically, compound 5b exhibited most remarkable cytotoxicities on A549 cells as well as MCF-7 and KATO III cells. Importantly, the cytotoxic effects of these compounds correlated with their Akt phosphorylation inhibitory activities.
authors: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Md Maqusood
authors: MM
authors: Alam
authors: Eun-Ha
authors: EH
authors: Joh
authors: Hyerim
authors: H
authors: Park
authors: Baek
authors: B
authors: Kim
authors: Dong-Hyun
authors: DH
authors: Kim
authors: Yong Sup
authors: YS
authors: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D003517:Cyclopentanes; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C026659:edelfosine; C105905:perifosine; C039128:miltefosine; D051057:Proto-Oncogene Proteins c-akt