{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:32:57Z","timestamp":1790173977632,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T00:00:00Z","timestamp":1460937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust"},{"name":"Medical Research Council"},{"name":"Mahidol-Liverpool PhD Scholarships"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2016,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross\u2010resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4\u2010trioxolane activity based protein\u2010profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90\u2009%) both qualitatively and semi\u2010quantitatively, suggesting a common mechanism of action that raises concerns about potential cross\u2010resistance liabilities.<\/jats:p>","DOI":"10.1002\/anie.201512062","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T12:57:12Z","timestamp":1460984232000},"page":"6401-6405","source":"Crossref","is-referenced-by-count":85,"title":["A Click Chemistry\u2010Based Proteomic Approach Reveals that 1,2,4\u2010Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile"],"prefix":"10.1002","volume":"55","author":[{"given":"Hanafy M.","family":"Ismail","sequence":"first","affiliation":[{"name":"Research Centre for Drugs and Diagnostics Liverpool School of Tropical Medicine  Pembroke Place Liverpool L3 5QA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Liverpool  Liverpool L69 7ZD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Panchana","sequence":"additional","affiliation":[{"name":"Research Centre for Drugs and Diagnostics Liverpool School of Tropical Medicine  Pembroke Place Liverpool L3 5QA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitthivut","family":"Charoensutthivarakul","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Liverpool  Liverpool L69 7ZD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo A.","family":"Biagini","sequence":"additional","affiliation":[{"name":"Research Centre for Drugs and Diagnostics Liverpool School of Tropical Medicine  Pembroke Place Liverpool L3 5QA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Research Centre for Drugs and Diagnostics Liverpool School of Tropical Medicine  Pembroke Place Liverpool L3 5QA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Liverpool  Liverpool L69 7ZD 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work was first presented at the Royal Society of Chemistry Biological & Medicinal Chemistry Sector Meeting on new perspectives in DMPK held at The Chemistry Centre Burlington House in London February 2014 seehttp:\/\/blogs.rsc.org\/books\/2014\/03\/06\/best-poster-rsc-bmcs-meetin\/."}],"container-title":["Angewandte Chemie International 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