lg190155 and Hypercalcemia

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.

Topics: Animals; Antineoplastic Agents; Caco-2 Cells; Calcitriol; Calcium; Cell Proliferation; Hep G2 Cells; Humans; Hypercalcemia; Inhibitory Concentration 50; Ligands; MCF-7 Cells; Mice, Inbred ICR; Molecular Docking Simulation; Pentanes; Rats; Receptors, Calcitriol; Structure-Activity Relationship