A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment.

Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. In vitro cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, In vivo study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day p < 0.001 with superior activity for lactoferrin-decorated formulation.

Regio- and Enantioselective Asymmetric Transfer Hydrogenation of One Carbonyl Group in a Diketone through Steric Hindrance.

On the basis of steric hindrance, one carbonyl group in a diketone can be reduced in a regioselective manner, with high enantioselectivity. The methodology can be extended to ketones with varied length of hydrocarbon chain spacing, and the products can be converted by oxidation to hydroxy esters or lactones without loss of enantiopurity.

Heterocycle-containing Noyori-Ikariya catalysts for asymmetric transfer hydrogenation of ketones.

The synthesis of a range of N-(heterocyclesulfonyl)-functionalised Noyori-Ikariya catalysts is described. The complexes were prepared through a short sequence from C2-symmetric 1,2-diphenylethylene-1,2-diamine (DPEN) and were characterised by a range of methods including X-ray crystallography. The complexes were active catalysts for the asymmetric transfer hydrogenation (ATH) of a range of acetophenone derivatives, giving products of high ee in most cases, with notably good results for ortho-substituted acetophenones.