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None tested compounds presented human erythrocyte cytotoxicity. The new compounds presented antipromastigote activity, where <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content><jats:sub>01<\/jats:sub> and <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content><jats:sub>02<\/jats:sub> derivatives presented significant antileishmanial activity, with better performance than the reference drugs (tri and pentavalent antimonials), with respective <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> values of 9.60\u00a0\u00b1\u00a03.19 and 10.95\u00a0\u00b1\u00a03.96\u00a0\u03bc<jats:sc>m<\/jats:sc>. Additionally, these two derivatives were effective against antimony\u2010resistant <jats:italic>Leishmania<\/jats:italic> (<jats:italic>Leishmania<\/jats:italic>) <jats:italic>amazonensis<\/jats:italic> strains. In addition, binding and fragmentation <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> assays were performed. It was observed that the antileishmanial activity of <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content><jats:sub>01<\/jats:sub> is not associated with <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation of the promastigote forms. However, it interacted with <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> with a binding constant of 10<jats:sup>4<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc><jats:sup>\u22121<\/jats:sup>. In partial least\u2010squares studies, it was observed that the most active compounds (<jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content><jats:sub>01<\/jats:sub> and <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content><jats:sub>02<\/jats:sub>) showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. Furthermore, the docking molecular studies showed interactions between thiophene\u2013acridine derivatives and the active site of pyruvate kinase enzyme with the major contribution of asparagine 152 residue for the interaction with thiophene moiety. Thus, the results suggested that the new thiophene\u2013acridine derivatives are promising molecules as potential drug candidates.<\/jats:p>","DOI":"10.1111\/cbdd.13176","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T20:47:02Z","timestamp":1518036422000},"page":"1141-1155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["New thiophene\u2013acridine compounds: Synthesis, antileishmanial activity, DNA binding, chemometric, and molecular docking studies"],"prefix":"10.1111","volume":"91","author":[{"given":"Vanessa","family":"de Lima Serafim","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses Departamento de Biologia Molecular Universidade Federal da Para\u00edba  Jo\u00e3o Pessoa PB Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Produtos Naturais e Sint\u00e9ticos Bioativos Universidade Federal da Para\u00edba  Jo\u00e3o Pessoa 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