Matsumoto Yotaro, Kittaka Atsushi, Chen Tai C
Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
Can J Physiol Pharmacol. 2015 May;93(5):333-48. doi: 10.1139/cjpp-2014-0452. Epub 2015 Mar 6.
The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3 or calcitriol), is known to inhibit the proliferation and invasiveness of many types of cancer cells, including breast, colon, pancreatic, prostate, and liver cancer cells. These findings support the use of 1α,25(OH)2D3 for the treatment of these types of cancer. However, 1α,25(OH)2D3 can cause hypercalcemia, so analogs of 1α,25(OH)2D3 that are less calcemic but exhibit more potent anti-tumor activity would be good candidates as therapeutic agents. Therefore, a series of 19-norvitamin D analogs, in which the methylidene group on C19 is replaced with 2 hydrogen atoms, have been synthesized by several laboratories. In our laboratory, we have designed and synthesized a series of 2α-functional group substituted 19-norvitamin D3 analogs and examined their anti-proliferative activity. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (MART-10 and MART-11) were found to be the most promising. Here, we review the rationale and approaches for the synthesis of different 19-norvitamin D analogs, and the pre-clinical studies using these analogs in breast cancer cells, in particular, we chose MART-10 for its potential application to the prevention and treatment of breast cancer.
维生素D3的活性形式，即1α,25 - 二羟基维生素D3（1α,25(OH)2D3或骨化三醇），已知可抑制多种癌细胞的增殖和侵袭，包括乳腺癌、结肠癌、胰腺癌、前列腺癌和肝癌细胞。这些发现支持使用1α,25(OH)2D3治疗这些类型的癌症。然而，1α,25(OH)2D3会导致高钙血症，因此，钙血症较低但具有更强抗肿瘤活性的1α,25(OH)2D3类似物将是很好的治疗药物候选物。因此，几个实验室已经合成了一系列19 - 去甲维生素D类似物，其中C19上的亚甲基被2个氢原子取代。在我们实验室，我们设计并合成了一系列2α - 官能团取代的19 - 去甲维生素D3类似物，并研究了它们的抗增殖活性。其中，2α - 和2β - (3 - 羟丙基)-1α,25 - 二羟基 - 19 - 去甲维生素D3（MART - 10和MART - 11）被发现是最有前景的。在此，我们综述了不同19 - 去甲维生素D类似物的合成原理和方法，以及在乳腺癌细胞中使用这些类似物的临床前研究，特别是我们选择MART - 10用于其在乳腺癌预防和治疗中的潜在应用。
