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Insights into structural modifications that can improve their therapeutic potential will be very valuable in this vibrant area of research. Our studies involving a library of quinolones which vary in substitution pattern at N1, C3, C6 and C7 positions have shown that the presence of adenine moiety at C7 can bring a noticeable improvement in activity compared to other heterocyclic groups at this location. The most potent compound emerged from this study showed IC<jats:sub>50<\/jats:sub> values of 0.38\u2005\u03bcM and 0.75\u2005\u03bcM against chloroquine\u2010sensitive and \u2010resistant (W2) strains, respectively. Docking analysis in the Q<jats:sub>o<\/jats:sub> site of cytochrome bc1 complex revealed the contribution of a key H\u2010bonding interaction from the adenine unit in target binding. This corroborates with compound\u2010induced loss of mitochondrial functions. These findings not only open avenues for further exploration of antimalarial potential of adenine\u2010modified quinolones, but also suggests broader opportunities during lead\u2010optimization against other antimalarial targets.<\/jats:p>","DOI":"10.1002\/cmdc.202100472","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T12:44:02Z","timestamp":1635597842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adenine Modification at C7 as a Viable Strategy to Potentiate the Antimalarial Activity of Quinolones"],"prefix":"10.1002","volume":"17","author":[{"given":"Jais","family":"Kurian","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Madras  Chennai 600036 Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varsha","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Molecular 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