TY - JOUR T1 - C15-functionalized 16-Ene-1α,25-dihydroxyvitamin D<sub>3</sub> is a New Vitamin D Analog with Unique Biological Properties JF - Anticancer Research JO - Anticancer Res SP - 311 LP - 317 VL - 32 IS - 1 AU - GO KUMAGAI AU - MASASHI TAKANO AU - KANAKO SHINDO AU - DAISUKE SAWADA AU - NOZOMI SAITO AU - HIROSHI SAITO AU - SHINJI KAKUDA AU - KEN-ICHIRO TAKAGI AU - MIDORI TAKIMOTO-KAMIMURA AU - KAZUYA TAKENOUCHI AU - TAI C. CHEN AU - ATSUSHI KITTAKA Y1 - 2012/01/01 UR - http://ar.iiarjournals.org/content/32/1/311.abstract N2 - The Δ16 structure as a vitamin D analog enhanced vitamin D receptor (VDR) binding affinity and induced significant cell differentiation, whereas its relative calcemic activity was reduced compared to 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). Methodologies available to introduce a double bond at C16-C17 of the D-ring on the seco-steroidal skeleton were limited; therefore, a new synthetic strategy was developed to obtain not only the Δ16 structure, but also a new C15-functional group. Since C15-functionalization was unprecedented in vitamin D analog studies, the hybrid structure of Δ16 and the C15-OH group at the D-ring may provide important information on the structure-activity relationship with vitamin D analogs. The synthesized 16-ene-2α-methyl-1α,15α,25-trihydroxyvitamin D3 showed almost 3-times higher VDR binding affinity and an equipotent level of osteocalcin promoter transactivation activity in human osteosarcoma cells as compared to 1α,25(OH)2D3. ER -