Chodyński Michał, Wietrzyk Joanna, Marcinkowska Ewa, Opolski Adam, Szelejewski Wiesław, Kutner Andrzej
Pharmaceutical Research Institute, 8 Rydygiera, 01-793, Warszawa, Poland.
Steroids. 2002 Aug;67(9):789-98. doi: 10.1016/s0039-128x(02)00038-7.
A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D(2) and D(3). The analogs were obtained by the Julia olefination of C(22)-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D(2) with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard.
合成了一系列1,25 - 二羟基麦角钙化醇（1 - 4）类似物，并对其体外抗增殖活性进行了筛选。基于先前获得的维生素D(2)和D(3)侧链修饰类似物的生物活性设计了新类似物的结构。这些类似物是通过C(22)-维生素D砜11与侧链醛15的Julia烯化反应得到的。分别测试了这些类似物对人乳腺癌细胞系T47D和MCF7以及人白血病细胞系HL - 60和小鼠白血病细胞系WEHI - 3的抗增殖活性。在目前这一系列具有单同系化和双不饱和侧链的1,25 - 二羟基维生素D(2)类似物中，类似物2（PRI - 1907）表现出最强的抗增殖活性。根据细胞系的不同，2的活性比用作标准的1,25 - 二羟胆钙化醇（骨化三醇）强3至150倍。
