Discovery of Potent Benzothiazole Inhibitors of Oxidoreductase NQO2, a Target for Inflammation and Cancer.

Inhibitors of NQO2 (NRH: quinone oxidoreductase) have potential application in several areas of medicine and pharmacology, including cancer, neurodegeneration (PD and AD), stroke, and diabetes. Here, resveratrol, a known inhibitor of NQO2, was used as the lead by replacing the double bond in resveratrol with a benzothiazole scaffold. Fifty-five benzothiazoles were designed as NQO2 inhibitors and synthesized, comprising five benzothiazole series with 3,5-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 3,4-dimethoxy, and 3,4,5-trimethoxy substituents, the key synthetic step being a Jacobson cyclisation with the appropriate thiobenzamide.

Targeting Hypoxia-Inducible Factor-1α in Pancreatic Cancer: siRNA Delivery Using Hyaluronic Acid-Displaying Nanoparticles.

Conventional anticancer therapies often lack specificity, targeting both cancerous and normal cells, which reduces efficacy and leads to undesired off-target effects. An additional challenge is the presence of hypoxic regions in tumors, where the Hypoxia Inducible Factor (HIF) transcriptional system drives the expression of pro-survival and drug resistance genes, leading to radio- and chemo-resistance. This study aims to explore the efficacy of targeted nanoparticle (NP)-based small interfering RNA (siRNA) therapies in downregulating these genes to enhance treatment outcomes in pancreatic cancer, a tumor type characterized by high CD44 expression and hypoxia.

SAR of Novel 3-Arylisoquinolinones: -Substitution on the Aryl Ring Dramatically Enhances Antiproliferative Activity through Binding to Microtubules.

A set of -substituted 3-arylisoquinolinones have been identified that show substantial cytotoxicity in breast, liver, lung and colon cancer cell lines; these are up to 700-fold more active than the corresponding analogues. These compounds were initially proposed as inhibitors of -ribosyl dihydronicotinamide (NRH): quinone oxidoreductase 2 (NQO2) but were found to be inactive against the enzyme. Instead, COMPARE analysis suggested that 6-fluoro-3-(-fluorophenyl)isoquinolin-1(2)-one () could mimic colchicine and interact with microtubules, a recognized target for cancer therapy.

Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin.

Background: High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism.

Binding and Internalization in Receptor-Targeted Carriers: The Complex Role of CD44 in the Uptake of Hyaluronic Acid-Based Nanoparticles (siRNA Delivery).

CD44 is an endocytic hyaluronic acid (HA) receptor, and is overexpressed in many carcinomas. This has encouraged the use of HA to design CD44-targeting carriers. This paper is about dissecting the mechanistic role of CD44.