{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:28:53Z","timestamp":1760059733505,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Graz"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The benzamide MMV030666 from MMV\u2019s Malaria Box Project, the starting point of herein presented study, was initially tested against various Plasmodium falciparum strains as well as Gram-positive and Gram-negative bacteria. It exhibits multi-stage antiplasmodial potencies and lacks resistance development. Methods: The favorable structural features from previous series were kept while the influence of the N-Boc-piperazinyl substituent per se, as well as its ring position and its replacement by various heteroaromatic rings, was evaluated. Thus, this paper describes the preparation of the MMV030666-derived 4\u2032-(piperazin-1-yl)benzanilides for the first time, exhibiting broad-spectrum activity not only against plasmodia but also various bacterial strains. Results: A series of insightful structure\u2013activity relationships were determined. Furthermore, pharmacokinetic and physicochemical parameters of the new compounds were determined experimentally or in silico. Drug-likeliness according to Lipinski\u2019s rules was calculated as well. Conclusions: A diarylthioether derivative of the lead compound was promisingly active against P. falciparum and exhibited broad-spectrum antibacterial activity against Gram-positive as well as Gram-negative bacteria. It is considered for testing against multi-resistant bacterial strains and in vivo studies.<\/jats:p>","DOI":"10.3390\/ph18071004","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T10:45:11Z","timestamp":1751539511000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Infective Properties, Cytotoxicity, and In Silico ADME Parameters of Novel 4\u2032-(Piperazin-1-yl)benzanilides"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-7852","authenticated-orcid":false,"given":"Theresa","family":"Hermann","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstra\u00dfe 1, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Harzl","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstra\u00dfe 1, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Wallner","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstra\u00dfe 1, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Prettner","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstra\u00dfe 1, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-0732","authenticated-orcid":false,"given":"Eva-Maria","family":"Pferschy-Wenzig","sequence":"additional","affiliation":[{"name":"Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstra\u00dfe 8, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Cal","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Kreuzstra\u00dfe 2, CH-4123 Allschwil, Switzerland"},{"name":"Faculty of Science, University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-1941","authenticated-orcid":false,"given":"Pascal","family":"M\u00e4ser","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Kreuzstra\u00dfe 2, CH-4123 Allschwil, Switzerland"},{"name":"Faculty of Science, University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-6673","authenticated-orcid":false,"given":"Robert","family":"Weis","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstra\u00dfe 1, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024). 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