Dissecting apoptosis the omics way

A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells

Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed

Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles

The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug

Platinum anticancer drug shortages

The platinum-based chemotherapy drugs cisplatin, carboplatin, and oxaliplatin remain, despite their long-term use, as integral components in the treatment of more than 25 different human cancers. As such, shortages in their supply can have serious health and societal impacts on both the outcome and welfare of patients and on the healthcare systems as a whole. As all three drugs are no longer under patent protection, they are supplied in Australia, the U.S. and the U.K. by between four and 17 different pharmaceutical companies, which reduces the risk of drug shortages. Determining the number and impact of platinum drug shortages in various regions of the world is difficult because legislation to monitor shortages has only been passed recently. All three drugs have suffered from shortages since 2017 with the most common shortage being due to discontinuation of the drug by the company. Other causes include production disruptions, changes in customer demand, problems in supply such as transport and storages, and other reasons. The median duration of drug shortage is 22 days (shortest and longest supply shortages are 3 and 79 days, respectively). Shortages appear to be rare in developed western countries and western European countries, but more common in eastern European countries where platinum drugs are never available or are available only half of the time. This project highlights the lack of information available on platinum drug shortages and the end to further examine platinum drug shortages in regions that are more likely to be impacted, such as Africa, south-east Asia, central and southern America, and the Middle East

Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design

The main task of the medicinal chemist is to design molecules that interact specifically with derailed or degenerating processes in a diseased organism, translating the available knowledge of pathobiochemical and physiological data into chemically useful information and structures. Current knowledge of the biological and chemical processes underlying diseases is vast and rapidly expanding. In particular the unraveling of the genome in combination with, for instance, the rapid development of structural biology has led to an explosion in available information and identification of new targets for chemotherapy. The task of translating this wealth of data into active and selective new drugs is an enormous, but realistic, challenge. It requires knowledge from many different fields, including molecular biology, chemistry, pharmacology, physiology, and medicine and as such requires a truly interdisciplinary approach. Ultimately, the goal is to design molecules that satisfy all the requirements for a candidate drug to function therapeutically. Therapeutic activity can then be achieved by an understanding of and control over structure and reactivity of the candidate drug through molecular manipulation

Anticancer Drug Development

British Journal of Cancer (2002) 86, 1665–1666. DOI: 10.1038/sj/bjc/6600309 www.bjcancer.co

Intercalative DNA binding of the marine anticancer drug variolin B

Variolin B is a rare marine alkaloid that showed promising anti-cancer activity soon after its isolation. It acts as a cyclin-dependent kinase inhibitor, although the precise mechanism through which it exerts the cytotoxic effects is still unknown. The crystal structure of a variolin B bound to a DNA forming a pseudo-Holliday junction shows that this compound can also contribute, through intercalative binding, to either the formation or stabilization of multi-stranded DNA forms.Peer ReviewedPostprint (published version

Curcumin-loaded zeolite as anticancer drug carrier: Effect of curcumin adsorption on zeolite structure

In this work we used a combination of different techniques to investigate the adsorption properties of curcumin by zeolite type A for potential use as an anticancer drug carrier. Curcumin is a natural water-insoluble drug that has attracted great attention in recent years due to its potential anticancer effect in suppressing many types of cancers, while showing a synergistic antitumor effect with other anticancer agents. However, curcumin is poorly soluble in aqueous solutions leading to the application of high drug dosage in oral formulations. Zeolites, inorganic crystalline aluminosilicates with porous structure on the nano- and micro-scale and high internal surface area, can be useful as pharmaceutical carrier systems to encapsulate drugs with intrinsic low aqueous solubility and improve their dissolution. Here, we explore the use of zeolite type A for encapsulation of curcumin, and we investigate its surface properties and morphology, before and after loading of the anticancer agent, using scanning electron microscopy (SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and UV-vis spectroscopy. Results are used to assess the loading efficiency of zeolite type A towards curcumin and its structural stability after loading