Tailored to the specific tumour microenvironment, which involves acidity and the overproduction of hydrogen peroxide, advanced nanotechnology has been introduced to generate the hydroxyl radical ( OH) primarily for tumour chemodynamic therapy (CDT) through the Fenton and Fenton-like reactions Numerous studies have investigated the enhancement of CDT efficiency, primarily the increase in the amount of  OH generated Notably, various strategies based on the Fenton reaction have been employed to enhance  OH generation, including nanomaterials selection, modulation of the reaction environment, and external energy fields stimulation, which are discussed systematically in this Minireview Furthermore, the potential challenges and the methods used to facilitate CDT effectiveness are also presented to support this cutting-edge research area

Chemodynamic Therapy: Tumour Microenvironment‑Mediated Fenton and Fenton‑like Reactions

Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria. ACTs comprise semisynthetic artemisinin derivatives paired with distinct chemical classes of longer acting drugs. These artemisinins are exceptionally potent against the pathogenic asexual blood stages of Plasmodium parasites and also act on the transmissible sexual stages. These combinations increase the rates of clinical and parasitological cures and decrease the selection pressure for the emergence of antimalarial resistance. This Review article discusses our current knowledge about the mode of action of ACTs, their pharmacological properties and the proposed mechanisms of drug resistance.

/pdf/artemisinin-based-combination-therapies-a-vital-tool-in-51niytr610.pdf

Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria

https://jeffreydachmd.com/wp-content/uploads/2014/10/Artemisinins_Sanjeev_Krishna_Trends_Pharmacological_Science_2008.pdf

Artemisinins: their growing importance in medicine

The present invention relates to a crystal structure of a plasma membrane proton pump type ATPase. The invention further describes method for identification of modulators of ATPases as well as uses of such modulators. Based on the provided three dimensional structure of the ATPase, various method, such as computer implemented methods may be used for identification of modulators, such putative modulators may be further analysed using in vitro and in vivo experiments to confirm there functionality. Several modulator interaction regions are described as target of regulation by ATPase modulators.

Crystal structure of a plasma membrane proton pump

Most cells have the inherent capacity to shift their reliance on glycolysis relative to oxidative metabolism, and studies in model systems have shown that targeting such shifts may be useful in treating or preventing a variety of diseases ranging from cancer to ischemic injury. However, we currently have a limited number of mechanistically distinct classes of drugs that alter the relative activities of these two pathways. We screen for such compounds by scoring the ability of >3,500 small molecules to selectively impair growth and viability of human fibroblasts in media containing either galactose or glucose as the sole sugar source. We identify several clinically used drugs never linked to energy metabolism, including the antiemetic meclizine, which attenuates mitochondrial respiration through a mechanism distinct from that of canonical inhibitors. We further show that meclizine pretreatment confers cardioprotection and neuroprotection against ischemia-reperfusion injury in murine models. Nutrient-sensitized screening may provide a useful framework for understanding gene function and drug action within the context of energy metabolism.

/pdf/nutrient-sensitized-screening-for-drugs-that-shift-energy-4l2u4bnv87.pdf

Judith H. Waknine

Papers

Current perspectives on the mechanism of action of artemisinins

Treatment of malaria in a mouse model by intranasal drug administration.