(2-phenylthiazol-4-yl)-(3-4-5-trimethoxyphenyl)methanone and Prostatic-Neoplasms

A novel microtubule destabilizer, substituted methoxybenzoyl-ary-thiazole (SMART)-100, was synthesized, which showed good anticancer activity in HepG2 cells. SMART-100 was able to circumvent multidrug resistance (MDR) and effectively inhibited the growth of cell lines that overexpress P-glycoprotein (P-gp). SMART-100 inhibited P-gp activity, which may be responsible for its ability to overcome MDR. Since SMART-100 is poorly soluble in water, it was formulated in polyethylene-b-poly(D,L-lactide) (PEG-PLA) micelles. The solubility of SMART-100 was increased by more than 1.1x10(5) folds. SMART-100 loaded PEG-PLA micelles could effectively inhibit HepG2 cell growth and arrest cell cycle progression at G2/M phase, followed by appearance of a sub-G1 phase, which is indicative of cell apoptosis. Increased Caspase-3 activity was also observed when HepG2 cells were treated with SMART-100. The anticancer activity of SMART-100 loaded PEG-PLA micelles was also evaluated on luciferase expressing C4-2-Luc cell lines by IVIS imaging. Our results suggest that SMART-100 has the potential to treat resistant cancers.

Topics: Apoptosis; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Hepatocellular; Caspase 3; Cell Cycle; Cell Proliferation; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Carriers; Drug Resistance, Neoplasm; Genes, Reporter; Hep G2 Cells; Humans; Inhibitory Concentration 50; Kinetics; Lactates; Liver Neoplasms; Luciferases; Male; Micelles; Polyethylene Glycols; Prostatic Neoplasms; Solubility; Technology, Pharmaceutical; Thiazoles; Tubulin Modulators