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A mutation in the kinase BRAF is observed in more than 66% of metastatic melanoma cases. Therefore, there is an urgent need to develop new BRAF\u2010mutant melanoma inhibitors. High\u2010dose chloroquine has been reported to have antitumour effects, but it often induces dose\u2010limiting toxicity. In this study, a series of chloroquine derivatives were synthesized, and lj\u20102\u201066\u00a0had the best activity and was selected for further investigation. Furthermore, the anti\u2010BRAF\u2010mutant melanoma effect and mechanism of this compound were explored. CCK\u20108 and colony formation assays indicated that lj\u20102\u201066\u00a0significantly inhibited the proliferation of BRAF\u2010mutant melanoma cells. Flow cytometry revealed that lj\u20102\u201066 induced G2\/M arrest in melanoma cells and promoted apoptosis. Furthermore, lj\u20102\u201066 increased the level of ROS in melanoma cells and induced DNA damage. Interestingly, lj\u20102\u201066 also played a similar role in BRAF inhibitor\u2010resistant melanoma cells. In summary, we found a novel chloroquine derivative, lj\u20102\u201066, that increased the level of ROS in melanoma cells and induced DNA damage, thus leading to G2\/M arrest and apoptosis. These findings indicated that lj\u20102\u201066\u00a0may become a potential therapeutic drug for melanoma harbouring BRAF\u00a0mutations.<\/jats:p>","DOI":"10.1111\/jcmm.17260","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T04:41:11Z","timestamp":1648183271000},"page":"2579-2593","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel chloroquine derivative suppresses melanoma cell growth by DNA damage through increasing ROS levels"],"prefix":"10.1111","volume":"26","author":[{"given":"Jiaoduan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology Xiangya Hospital, Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital  Changsha China"},{"name":"National Clinical Research Center for 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