99520-09-9Relevant academic research and scientific papers
Preparation method of 3, 5-dichlorobenzaldehyde and carboxamide triazole intermediate
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, (2021/02/10)
The invention relates to a preparation method of 3, 5-dichlorobenzene methanol and a carboxylamine triazole intermediate. The preparation method of the 3, 5-dichlorobenzene methanol comprises the following steps: mixing the 3, 5-dichlorobenzene methanol with potassium borohydride and zinc chloride in a solvent, heating to reflux, and carrying out reduction reaction; after the reduction reaction isfinished, concentrating to prepare a crude product; and adding a hydrochloric acid aqueous solution and toluene into the crude product for extraction or adding toluene for extraction, collecting a toluene phase, washing the toluene phase with an alkaline aqueous solution and water to be neutral, then concentrating the toluene phase to be dry, and recrystallizing the obtained solid with n-hexane.According to the synthetic method of 3, 5-dichlorobenzene methanol, the raw materials are easy to obtain, the reaction conditions are mild and easy to control, the product is easy to purify, and the yield of the product is high.
Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex i
Allen, Timothy E. H.,Chung, Injae,Fischer, Peter,Hardy, Rachel,Harvey, Robert F.,Hirst, Judy,Kellam, Barrie,Macfarlane, Marion,Mistry, Sarah,Pryde, Kenneth R.,Serreli, Riccardo,Stephenson, Zo? A.,Stoneley, Mark,Willis, Anne E.
, (2020/06/10)
Disruption of mitochondrial function selectively targets tumour cells that are dependent on oxidative phosphorylation. However, due to their high energy demands, cardiac cells are disproportionately targeted by mitochondrial toxins resulting in a loss of cardiac function. An analysis of the effects of mubritinib on cardiac cells showed that this drug did not inhibit HER2 as reported, but directly inhibits mitochondrial respiratory complex I, reducing cardiac-cell beat rate, with prolonged exposure resulting in cell death. We used a library of chemical variants of mubritinib and showed that modifying the 1H-1,2,3-triazole altered complex I inhibition, identifying the heterocyclic 1,3-nitrogen motif as the toxicophore. The same toxicophore is present in a second anti-cancer therapeutic carboxyamidotriazole (CAI) and we demonstrate that CAI also functions through complex I inhibition, mediated by the toxicophore. Complex I inhibition is directly linked to anti-cancer cell activity, with toxicophore modification ablating the desired effects of these compounds on cancer cell proliferation and apoptosis.
