药物化学

Oxidative stress, a result of the overproduction and buildup of free radicals, is the main cause of a number of degenerative diseases, including atherosclerosis, cancer, ageing, cardiovascular, and inflammatory disorders. Polyphenols, which are naturally occurring antioxidants, have a wide range of biological effects, including antibacterial, anticancer, antiviral, antifungal, anticholesterol lowering, and ulcer healing.

Chemical biology and drug development are both hot on the subject of target deconvolution of phenotypic tests. Finding targets for chemicals that generate intriguing phenotypic readouts is the ultimate objective. To help with this process, numerous experimental and computational techniques have been developed. According to a commonly used computational method, potential targets for new active molecules are inferred based on how chemically similar those molecules are to substances that have activity against established targets. Using chemical cancer cell line screens as a model system for phenotypic tests, we offer a molecular scaffold-based alternative for similarity-based target deconvolution in this article. Analog series-based (ASB) scaffold, a new form of scaffold, was employed for substructure-based similarity assessment. Target assignment centred on ASB was compared to conventional scaffolds and compound-based similarity analyses.

Due to their ability to modify signalling pathways by binding to phospho-writers, erasers, and readers like proteins with SH2 and PTB domains, phosphotyrosine-containing compounds are the focus of considerable research. In order to research protein phosphorylation and dephosphorylation, phosphotyrosine derivatives are helpful chemical tools. As a result, they are appealing starting points for the creation of binding ligands, chemical probes to study biology, and inhibitor and degrader drug design. Physiologically stable phosphonate-based phosphotyrosine analogues are useful in a wide range of applications to overcome the enzymatic lability of the phosphate group.

Anthracyclines are among the most effective anticancer drugs ever developed. Cardiotoxicity is a well-known anthracycline side effect that restricts the total amount of medication given and can result in heart failure in some patients. Anthracyclines are thought to cause cardiotoxicity after one electron reduction with ROS overproduction or two electron reduction with conversion to C-13 alcohol metabolites, according to the pathophysiology of anthracycline induced cardiotoxicity. Overproduction of Reactive Oxygen Species (ROS) is likely to be the cause of anthracycline induced acute cardiotoxicity, but not all aspects of progressive cardiomyopathy. Secondary alcohol metabolites can play an important role in promoting cardiotoxicity's progression to end stage cardiomyopathy and congestive heart failure.

This review will provide an overview of the molecular mechanisms responsible for anthracycline induced cardiotoxicity focusing on the pathogenic role of Reactive Oxygen Species (ROS) and/or anthracycline secondary alcohol metabolites; and, lastly, on the most promising strategies to minimize or prevent anthracycline induced cardiotoxicity.

Micro needle patches are the novel dosage form in transdermal drug delivery systems with improved penetration to skin. In this study we fabricated micro needle patches containing azathioprine an immunosuppressant drug by using polymer thiolated chitosan that in turn was developed by adding thiol group to chitosan. These micro needle patches were further evaluated for their mechanical, physical and chemical parameters. The optimized micro needle patch having 225 needles with 665 μm length, 90 μm width showed good penetration i.e 84% and better percent elongation. In-vitro and ex-vivo penetration studies on rat skin using Franz diffusion cell showed sustained release of (85%) azathioprine in its comparative study with azathioprine ointment. HPLC analysis also showed 91.7% release of drug from optimized formulation of micro needle patch. Finally the recent progress proved that micro needle patches of thiolated chitosan loaded with azathioprine for transdermal drug delivery have the potential to show therapeutic outcomes with improved bioavailability and sustained release of drug over a longer period.