The bacterial thiopeptide thiostrepton. An update of its mode of action, pharmacological properties and applications

Eur J Pharmacol. 2021 Dec 2:174661. doi: 10.1016/j.ejphar.2021.174661. Online ahead of print.ABSTRACTThe bacterial thiopeptide thiostrepton (TS) is used as a veterinary medicine to treat bacterial infections. TS is a protein translation inhibitor, essentially active against Gram-positive bacteria and some Gram-negative bacteria. In procaryotes, TS abrogates binding of GTPase elongation factors to the 70S ribosome, by altering the structure of rRNA-L11 protein complexes. TS exerts also antimalarial effects by disrupting protein synthesis in the apicoplast genome of Plasmodium falciparum. Interestingly, the drug targets both the infectious pathogen (bacteria or parasite) and host cell, by inducing endoplasmic reticulum stress-mediated autophagy which contributes to enhance the host cell defense. In addition, TS has been characterized as a potent chemical inhibitor of the oncogenic transcription factor FoxM1, frequently overexpressed in cancers or other diseases. The capacity of TS to crosslink FoxM1, and a few other proteins such as peroxiredoxin 3 (PRX3) and the 19S proteasome, contributes to the anticancer effects of the thiopeptide. The anticancer activities of TS evidenced using diverse tumor cell lines, in vivo models and drug combinations are reviewed here, together with the implicated targets and mechanisms. The difficulty to formulate TS is a drag on the pharmaceutical development of the natural product. However, the design of hemisynthetic analogues and the use of mice...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research

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ChemMedChem. 2022 Jan 9. doi: 10.1002/cmdc.202100784. Online ahead of print.ABSTRACTIn this work is reported the synthesis of 16 new compounds obtained from kokusaginine and flindersiamine, the main alkaloids isolated from the bark of Balfourodendron riedelianum . The activity of the compounds against axenic cultures of Trypanosoma cruzi epimastigtotes and trypomastigotes, as well as intracellular amastigotes, is described, together with their cytotoxic activity against three different human cell lines. The synthetic strategy for the preparation of the new compounds was based on the reactivity at the position C-4 of the fu...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
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Source: Amino Acids - Category: Biochemistry Authors: Source Type: research
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Source: Molecular Biology Reports - Category: Molecular Biology Authors: Source Type: research
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Source: The Scientist - Category: Science Tags: News & Opinion Source Type: news
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Source: Mini Reviews in Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
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Source: RSC - CrystEngComm latest articles - Category: Chemistry Authors: Source Type: research
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Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
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Source: Annals of Clinical and Laboratory Science - Category: Laboratory Medicine Authors: Source Type: research
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