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Replacement of one of the aryl <jats:italic>meta<\/jats:italic>\u2010methoxy groups by halogens such as chlorine, bromine and iodine led to distinctly increased antiparasitic activities. For instance, the new bromo\u2010 and iodo\u2010substituted compounds <jats:bold>3\u2009b\/c<\/jats:bold> and <jats:bold>4\u2009b\/c<\/jats:bold> showed strong activity against <jats:italic>L.\u2005major<\/jats:italic> promastigotes (IC<jats:sub>50<\/jats:sub>=4.5\u20135.8\u2005\u03bcM). Their activities against <jats:italic>L.\u2005major<\/jats:italic> amastigotes were moderate. In addition, the new compounds <jats:bold>3\u2009b<\/jats:bold>, <jats:bold>3\u2009c<\/jats:bold>, and <jats:bold>4\u2009a<\/jats:bold>\u2013<jats:bold>c<\/jats:bold> exhibited high activity against <jats:italic>T.\u2005gondii<\/jats:italic> parasites (IC<jats:sub>50<\/jats:sub>=2.0\u20133.5\u2005\u03bcM) with considerable selectivities when taking their effects on non\u2010malignant Vero cells into account. Notable antitrypanosomal activity against <jats:italic>Trypanosoma brucei<\/jats:italic> was also found for <jats:bold>4\u2009b<\/jats:bold>. Antifungal activity against <jats:italic>Madurella mycetomatis<\/jats:italic> was observed for compound <jats:bold>4\u2009c<\/jats:bold> at higher doses. Quantitative structure\u2010activity relationship (QSAR) studies were carried out, and docking calculations of test compounds bound to tubulin revealed binding differences between the 2\u2010pyrrolidone and 2\u2010piperidone derivatives. Microtubules\u2010destabilizing effects were observed for <jats:bold>4\u2009b<\/jats:bold> in <jats:italic>T.\u2005b.\u2005brucei<\/jats:italic> cells.<\/jats:p>","DOI":"10.1002\/cmdc.202300132","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:40:23Z","timestamp":1680770423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine\u2010Type Cinnamide Derivatives: Booster Effect by Halogen Substituents"],"prefix":"10.1002","volume":"18","author":[{"given":"Tariq A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition College of Applied Health Sciences Qassim University  Ar Rass 51921 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim S.","family":"Al Nasr","sequence":"additional","affiliation":[{"name":"Department of Biology College of Science and Arts Qassim University  Unaizah 51911 Saudi Arabia"},{"name":"Department of Science Laboratories College of Science and Arts Qassim University  Ar Rass 51921 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed S.","family":"Koko","sequence":"additional","affiliation":[{"name":"Department of Science Laboratories College of Science and Arts Qassim University  Ar Rass 51921 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Disease Erasmus MC University Medical Center Rotterdam  Dr. Molewaterplein 40 3015 GD Rotterdam (The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Genetics University Bayreuth  Universit\u00e4tsstrasse 30 95440 Bayreuth Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Brehm","sequence":"additional","affiliation":[{"name":"Department of Genetics University Bayreuth  Universit\u00e4tsstrasse 30 95440 Bayreuth Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridha","family":"Ben Said","sequence":"additional","affiliation":[{"name":"Laboratoire de Caract\u00e9risations Applications et Mod\u00e9lisations des Mat\u00e9riaux Facult\u00e9 des Sciences de Tunis Universit\u00e9 Tunis El Manar  Tunis Tunisia"},{"name":"Department of Chemistry College of Science and Arts at Ar Rass Qassim University  P.O. 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