title: Synthesis and biological evaluation of cyclopentane-linked alkyl phosphocholines as potential anticancer agents that act by inhibiting Akt phosphorylation.
abstract: Three new series of novel alkylphosphocholine (APC) derivatives containing a cyclopentane ring near the phosphocholine head group were synthesized. In the first set of analogues, the phosphocholine head group was attached to the secondary alcohol of trans-2-(hydroxymethyl)cyclopentanol, whereas in the second and third sets of analogues, the phosphocholine head group was linked to the primary alcohol of trans- and cis-2-(hydroxymethyl)cyclopentanol, respectively. Of the compounds synthesized, compound 6d most potently inhibited Akt phosphorylation with an IC(50) value of 3.6 μM, its potency was greater than the reference compounds miltefosine, perifosine, and erufosine. Compounds 6b and 6d exhibited the most potent growth-inhibitory effects on A549, MCF-7, and KATO-III human cancer cell lines. These compounds also showed more active anti-proliferative effects than the reference compounds. Importantly, the cytotoxic effects of these compounds on A549 cell line were proportional to their abilities to inhibit Akt phosphorylation, which supports that these synthesized APC compounds are novel inhibitors of the Akt cell survival pathway.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Md Maqusood
authors.initials: MM
authors.lastname: Alam
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Joh
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
authors.forename: Yeon Il
authors.initials: YI
authors.lastname: Oh
authors.forename: Jongki
authors.initials: J
authors.lastname: Hong
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D003517:Cyclopentanes; D010767:Phosphorylcholine; D051057:Proto-Oncogene Proteins c-akt