title: Structure-activity relationships of 2'-modified-4'-selenoarabinofuranosyl-pyrimidines as anticancer agents.
abstract: Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Jin-Hee
authors: JH
authors: Kim
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Jinha
authors: J
authors: Yu
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Varughese
authors: V
authors: Alexander
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Jung Hee
authors: JH
authors: Choi
authors: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jayoung
authors: J
authors: Song
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Hyuk Woo
authors: HW
authors: Lee
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Hea Ok
authors: HO
authors: Kim
authors: Department of Chemistry, The University of Suwon, Kyunggi-do 445-743, Republic of Korea.
authors: Jungwon
authors: J
authors: Choi
authors: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sang Kook
authors: SK
authors: Lee
authors: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea; College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: lakjeong@snu.ac.kr.
authors: Lak Shin
authors: LS
authors: Jeong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D012643:Selenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D012643:Selenium
keywords: 4′-Selenonucleosides; Antimetabolite; Mitsunobu reaction; Stereoselective fluorination; Structure–activity relationship