---
title: "3-Hydroxypropanamidines: From Antiplasmodial Leads to a Novel Antibacterial Scaffold"
id: "biorxiv-15-3-hydroxypropanamidines-from-antiplasmodial-leads-to-a-novel-antibacterial"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-15-3-hydroxypropanamidines-from-antiplasmodial-leads-to-a-novel-antibacterial"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.20.752996v1?rss=1"
published_at: "2026-09-21T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 3-Hydroxypropanamidines: From Antiplasmodial Leads to a Novel Antibacterial Scaffold
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-15-3-hydroxypropanamidines-from-antiplasmodial-leads-to-a-novel-antibacterial
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.20.752996v1?rss=1)
- **Published At:** 2026-09-21T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Researchers evaluated three **3-hydroxypropanamidine** derivatives (4: **BLK278**, 5: **BLK280**, 6: **TKK088**) originally developed as antiplasmodial agents for antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria. - Compound 6 (TKK088) showed the strongest activity against **Staphylococcus aureus**, including multidrug-resistant MRSA and VISA strains. - Compound 5 (BLK280) demonstrated the broadest antibacterial spectrum, with activity against Gram-negative pathogens including **Escherichia coli**, **Acinetobacter baumannii**, **Klebsiella pneumoniae**, **Klebsiella aerogenes**, and **Shigella sonnei**. - Cytotoxicity was assessed in HUVEC and HAOSMC cells; compounds 4 (BLK278) and previously reported 7 (TKK129) had the most favorable overall cytotoxicity profiles among those tested. - Selectivity indices for activity against S. aureus were under 2.5 for all compounds, with clear, cell-type-dependent differences observed for every compound tested, including **mefloquine**, highlighting the need to improve antibacterial selectivity. - In vitro pharmacokinetic profiling showed high plasma protein binding and good human microsomal and plasma stability for all three 3-hydroxypropanamidines. - Gel-based proteomic analysis of treated bacteria revealed a pronounced impact on the bacterial cell envelope; acute proteomic responses were pleiotropic and align with prior reports implicating **F0F1-ATPase** as a potential molecular target of mefloquine in Streptococcus pneumoniae. - The study is reported as a preprint and has not undergone peer review. Details beyond the abstract, such as exact MIC values, numerical cytotoxicity data, experimental conditions, and full methodological parameters, were not reported in the source abstract.
## Clinical Analysis & Structured Key Points
3-Hydroxypropanamidines: from antiplasmodial leads to a novel antibacterial scaffold | bioRxiv Skip to main content New Results 3-Hydroxypropanamidines: from antiplasmodial leads to a novel antibacterial scaffold Lara-Sophie Kaufmann , André Schultz , Noemi Wladarz , View ORCID Profile Tanja Gangnus , Beate Lungerich , Tanja C. Knaab , André Haase , View ORCID Profile Lea Joswig , Finn Dressler , Pascal Dietze , Ralf Benndorf , Björn B. Burckhardt , View ORCID Profile Thomas Kurz , View ORCID Profile Julia Elisabeth Bandow doi: https://doi.org/10.64898/2026.09.20.752996 Lara-Sophie Kaufmann 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site André Schultz 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Noemi Wladarz 2 Heinrich-Heine Universität Düsseldorf, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tanja Gangnus 3 University of Muenster, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tanja Gangnus Beate Lungerich 2 Heinrich-Heine Universität Düsseldorf, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tanja C. Knaab 2 Heinrich-Heine Universität Düsseldorf, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site André Haase 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lea Joswig 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lea Joswig Finn Dressler 3 University of Muenster, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pascal Dietze 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ralf Benndorf 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Björn B. Burckhardt 3 University of Muenster, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thomas Kurz 2 Heinrich-Heine Universität Düsseldorf, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thomas Kurz Julia Elisabeth Bandow 1 Ruhr University Bochum, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Julia Elisabeth Bandow For correspondence: julia.bandow{at}rub.de Abstract Info/History Metrics Supplementary material Preview PDF Abstract Arylamino alcohols constitute an established class of antimalarial agents. While this class is best known for its potent antiplasmodial activity, selected members, most notably mefloquine, have also been reported to exhibit antibacterial activity. Structurally related 3-hydroxypropanamidines were developed as highly potent antimalarial agents. Here, we explored the antibacterial activity of three 3-hydroxypropanamidines ( 4 ( BLK278 ), 5 ( BLK280 ), and 6 ( TKK088 )) against clinically relevant Gram-positive and Gram-negative bacteria and investigated their cytotoxicity, in vitro pharmacokinetic properties, and proteome-based bacterial response to treatment. We observed good antibacterial activity against Staphylococcus aureus , with 6 ( TKK088 ) displaying the highest activity against multidrug-resistant MRSA and VISA strains. 5 ( BLK280 ) demonstrated the greatest spectrum of activity acting also against clinically relevant Gram-negative strains of Escherichia coli , Acinetobacter baumannii , Klebsiella pneumoniae , Klebsiella aerogenes , and Shigella sonnei . In cytotoxicity assays with HUVEC and HAOSMC cells, 4 ( BLK278 ) and the previously reported 7 ( TKK129 ) showed the most favourable overall profiles among the investigated 3-hydroxypropanamidines. The selectivity indices for S. aureus were below 2.5 with clear cell-type-dependent differences for all compounds including mefloquine, suggesting that improving antibacterial selectivity is an important objective for further optimization. In vitro pharmacokinetics showed high plasma protein binding and good human microsomal and plasma stability for all three 3-hydroxypropanamidines. Gel-based proteomic responses revealed a strong impact on the bacterial cell envelope. The observed acute proteomic responses reflect pleiotropic effects and are consistent with earlier reports implicating F 0 F 1 -ATPase as a potential molecular target of mefloquine in Streptococcus pneumoniae . Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64 , RTG 2341 German Federal State of North Rhine-Westphalia and the European Union, European Regional Development Fund , EFRE-0200598 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Back to top Previous Next Posted September 21, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Burckhardt , Thomas Kurz , Julia Elisabeth Bandow bioRxiv 2026.09.20.752996; doi: https://doi.org/10.64898/2026.09.20.752996 Share This Article: Copy Citation Tools 3-Hydroxypropanamidines: from antiplasmodial leads to a novel antibacterial scaffold Lara-Sophie Kaufmann , André Schultz , Noemi Wladarz , Tanja Gangnus , Beate Lungerich , Tanja C. Knaab , André Haase , Lea Joswig , Finn Dressler , Pascal Dietze , Ralf Benndorf , Björn B. Burckhardt , Thomas Kurz , Julia Elisabeth Bandow bioRxiv 2026.09.20.752996; doi: https://doi.org/10.64898/2026.09.20.752996 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8017) Biochemistry (18744) Bioengineering (14893) Bioinformatics (44458) Biophysics (22612) Cancer Biology (19728) Cell Biology (26906) Clinical Trials (138) Developmental Biology (13971) Ecology (21008) Epidemiology (2067) Evolutionary Biology (25457) Genetics (16172) Genomics (23519) Immunology (18717) Microbiology (42520) Molecular Biology (18064) Neuroscience (93524) Paleontology (700) Pathology (2982) Pharmacology and Toxicology (5100) Physiology (8118) Plant Biology (16000) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10237) Zoology (2391)
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