Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid loaded onto fluorescent mesoporous silica nanoparticles for the location and therapy of nasopharyngeal carcinoma.

Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is a diterpenoid that is isolated and purified from the Chinese herbal medicine Pteris semipinnata L., and is known to exert antitumour activity in several kinds of malignant cancer cells by leading cancer cells to apoptosis. However, the antitumour effect of 5F in vivo is rarely reported due to the complexity of the physiological environment and limitations of 5F as a small anticancer drug. In the present study, we utilized FITC-doped nanoparticles for the accumulation and delivery of 5F in nasopharyngeal carcinoma CNE2 tumours transplanted in nude mice by the enhanced permeation and retention (EPR) effect. In vivo studies demonstrated that nanoparticles could efficiently deliver 5F in CNE2 transplanted tumours, and the tumour growth was effectively inhibited by the drug-loaded nanoparticles with minimal side effects. The study indicated the benefits of combining well-studied nanoparticles with traditional herbal medicine treatment and establishes a delivery platform for 5F chemotherapy.

Discovery of a Conformationally Constrained Oxazolidinone with Improved Safety and Efficacy Profiles for the Treatment of Multidrug-Resistant Tuberculosis.

Tuberculosis (TB) remains a serious public health challenge, and the research and development of new anti-TB drugs is an essential component of the global strategy to eradicate TB. In this work, we discovered a conformationally constrained oxazolidinone 19c with improved anti-TB activity and safety profile through a focused lead optimization effort. Compound 19c displayed superior in vivo efficacy in a mouse TB infection model compared to linezolid and sutezolid. The druggability of compound 19c was demonstrated in a panel of assays including microsomal stability, cytotoxicity, cytochrome P450 enzyme inhibition, and pharmacokinetics in animals. Compound 19c demonstrated an excellent safety profile in a battery of safety assays, including mitochondrial protein synthesis, hERG K+, hCav1.2, and Nav1.5 channels, monoamine oxidase, and genotoxicity. In a 4 week repeated dose toxicology study in rats, 19c appeared to have less bone marrow suppression than linezolid, which has been a major liability of the oxazolidinone class.