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Drug resistance has been addressed using a variety of strategies, such as targeted therapies, the hybrid drug idea, the development of advanced analogues of pre\u2010existing drugs, and the hybrid model of resistant strains control mechanisms. Additionally, the demand for discovering new potent drugs grows due to the prolonged life cycle of conventional therapy brought on by the emergence of resistant strains and ongoing changes in existing therapies. The 1,2,4\u2010trioxane ring system in artemisinin (ART) is the most significant endoperoxide structural scaffold and is thought to be the key pharmacophoric moiety required for the pharmacodynamic potential of endoperoxide\u2010based antimalarials. Several derivatives of artemisinin have also been found as potential treatments for multidrug\u2010resistant strain in this area. Many 1,2,4\u2010trioxanes, 1,2,4\u2010trioxolanes, and 1,2,4,5\u2010tetraoxanes derivatives have been synthesised as a result, and many of these have shown promise antimalarial activity both in vivo and in vitro against Plasmodium parasites. As a consequence, efforts to develop a functionally straight\u2010forward, less expensive, and vastly more effective synthetic pathway to trioxanes continue. This study aims to give a thorough examination of the biological properties and mode of action of endoperoxide compounds derived from 1,2,4\u2010trioxane\u2010based functional scaffolds. The present system of 1,2,4\u2010trioxane, 1,2,4\u2010trioxolane, and 1,2,4,5\u2010tetraoxane compounds and dimers with potentially antimalarial activity will be highlighted in this systematic review (January 1963\u2013December 2022).<\/jats:p>","DOI":"10.1002\/med.21979","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T12:06:37Z","timestamp":1684929997000},"page":"66-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["An overview on the antimalarial activity of 1,2,4\u2010trioxanes, 1,2,4\u2010trioxolanes and 1,2,4,5\u2010tetraoxanes"],"prefix":"10.1002","volume":"44","author":[{"given":"Monika","family":"Shukla","sequence":"first","affiliation":[{"name":"Department of Chemistry Banasthali University Newai Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Rathi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Banasthali University Newai Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Hassam","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemveda Life Sciences Pvt Ltd Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Chemistry Mohanlal Sukhadia University Udaipur Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manvika","family":"Karnatak","sequence":"additional","affiliation":[{"name":"Department of Chemistry Banasthali University Newai Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Rawat","sequence":"additional","affiliation":[{"name":"School of Chemistry, Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2142-2459","authenticated-orcid":false,"given":"Ved Prakash","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Chemistry Banasthali University Newai Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0327-4"},{"key":"e_1_2_13_3_1","unstructured":"WHO. 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