2. Academic Validation
  3. Novel nonsecosteroidal VDR ligands with phenyl-pyrrolyl pentane skeleton for cancer therapy

Novel nonsecosteroidal VDR ligands with phenyl-pyrrolyl pentane skeleton for cancer therapy

  • Eur J Med Chem. 2016 Jan 1:107:48-62. doi: 10.1016/j.ejmech.2015.10.042.
Zhixin Ge 1,  Meixi Hao 1,  Meng Xu 1,  Zhigui Su 1,  Zisheng Kang 1,  Lingjing Xue 2,  Can Zhang 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Nature Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
  • 2 State Key Laboratory of Nature Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China. Electronic address: xuelingjing65@163.com.
  • 3 State Key Laboratory of Nature Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China. Electronic address: zhangcan@cpu.edu.cn.
PMID: 26562542 DOI: 10.1016/j.ejmech.2015.10.042
Abstract

A series of nonsecosteroidal vitamin D3 receptor (VDR) ligands with phenyl-pyrrolyl pentane skeleton were synthesized for Cancer therapy. In contrast to 1α,25-dihydroxyvitamin D3 (Calcitriol), these VDR ligands exhibited anti-proliferative activity without inducing hypercalcemia. These compounds were evaluated for vitamin D3-agonistic ability and anti-proliferative activity in vitro. Among them, compounds 5k and 5i exhibited equivalent vitamin D3-agonistic activity compared with Calcitriol. Meanwhile, compound 5k displayed promising inhibiting profile against MCF-7, HepG-2 and Caco-2 with IC50 values of 0.00586 μM, 0.176 μM, and 1.01 μM (Calcitriol: 5.58 μM, 80.83 μM and 4.46 μM) respectively. Compound 5i inhibited proliferation of PC-3 with IC50 value of 0.00798 μM (Calcitriol: 17.25 μM). Additionally, neither of these compounds significantly elevated serum calcium in rats.

Keywords

Anti-proliferation; Cancer therapy; Hypercalcemia; Nonsecosteroid; Phenyl-pyrrolyl pentane skeleton; VDR; Vitamin D(3)-agonistic activity.

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