calcitriol and pentane

Modulating the vitamin D receptor (VDR) is an effective way to treat for cancer. We previously reported a potent non-secosteroidal VDR modulator (sw-22) with modest anti-tumor activity, which could be due to its undesirable physicochemical and pharmacokinetic properties. In this study, we investigated the structure-activity and structure-property relationships around the 2'-hydroxyl group of sw-22 to improve the physicochemical properties, pharmacokinetic properties and anti-tumor activity. Compounds 19a and 27b, the potent non-secosteroidal VDR modulators, were identified as the most effective molecules in inhibiting the proliferation of three cancer cell lines, particularly breast cancer cells, with a low IC

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasms, Experimental; Pentanes; Receptors, Calcitriol; Selective Estrogen Receptor Modulators; Structure-Activity Relationship

Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components and results in impaired liver function. Vitamin D plays a critical role in the development of liver fibrosis as it inhibits transforming growth factor β1 (TGFβ1)-induced excessive deposition of ECM in activated hepatic stellate cells (HSCs). Here, a series of novel nonsecosteroidal vitamin D receptor (VDR) agonists with phenyl-pyrrolyl pentane skeleton was designed and synthesized. Among them, seven compounds including 15a exhibited more efficient inhibitory activity in collagen deposition and fibrotic gene expression. Histological examination results displayed that compound 15a treatment prevented the development of hepatic fibrosis that induced by carbon tetrachloride (CCl

Topics: Animals; Cell Line; Chemistry Techniques, Synthetic; Drug Design; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Models, Molecular; Pentanes; Protein Conformation; Pyrroles; Receptors, Calcitriol

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