Preparation of new 1,3-dibenzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities

Markus Petritsch; Werner Seebacher; Noor-Ul-Amin Mohsin; Johanna Dolensky; Patrick Hochegger; Marcel Kaiser; Pascal Mäser; Ferdinand Belaj; Robert Saf; Nadine Kretschmer; Muaaz Alajlani; Adelheid Brantner; Rudolf Bauer; Wolfgang Schühly; Robert Weis

doi:10.1016/j.ejmech.2020.112969

Preparation of new 1,3-dibenzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities

Eur J Med Chem. 2021 Jan 15:210:112969. doi: 10.1016/j.ejmech.2020.112969. Epub 2020 Oct 29.

Authors

Affiliations

¹ Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstrasse 1, 8010 Graz, Austria.
² Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstrasse 1, 8010 Graz, Austria. Electronic address: we.seebacher@uni-graz.at.
³ Faculty of Pharmaceutical Sciences, Government College University, Allama Iqbal Road, 38000, Faisalabad, Pakistan.
⁴ Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland; University of Basel, Petersplatz 1, 4003, Basel, Switzerland.
⁵ Institute of Chemistry, University of Graz, Universitätsplatz 1, 8010, Graz, Austria.
⁶ Institute for Chemistry and Technology of Organic Materials (ICTM), Graz University of Technology, Stremayrgasse 9, 8010, Graz, Austria.
⁷ Institute of Pharmaceutical Sciences, Pharmacognosy, University of Graz, Universitätsplatz 4, 8010, Graz, Austria.
⁸ Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, Hoher Weg 8, 06120, Halle, Germany.
⁹ Institute of Zoology, Pharmacognosy, University of Graz, Universitätsplatz 2/1, 8010, Graz, Austria.

PMID: 33148495
DOI: 10.1016/j.ejmech.2020.112969

Abstract

New 1,3 dibenzyl -tetrahydropyridinylidene ammonium salts have been prepared from unsubstituted or N-benzylated tetrahydropyridinylidene ammonium salts. The antiplasmodial and antitrypanosomal activities as well as their cytotoxic effects were determined using microplate assays. In addition, their activities against two gram positive and two gram negative bacteria strains and a yeast strain were examined. Furthermore, anticancer effects against two cell lines were investigated. Physicochemical parameters were calculated and structure-activity-relationships discussed. One compound showed antiplasmodial activity against a multiresistant strain of Plasmodium falciparum in subnanomolar concentration. Antitrypanosomal activities were detected in low nanomolar concentrations. A single compound was active against grampositive and gramnegative bacteria, as well as yeast. One compound inhibited the growth of a HCT cell line in low concentration.

Keywords: 1,3 dibenzyl tetrahydropyridinylidene ammonium salts; Antibacterial; Anticancer; Antiplasmodial; Antitrypanosomal.

MeSH terms

Animals
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Antimalarials / chemical synthesis
Antimalarials / chemistry
Antimalarials / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Candida albicans / drug effects
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Epidermis / drug effects
Escherichia coli / drug effects
Female
Humans
Mice
Microbial Sensitivity Tests
Molecular Structure
Parasitic Sensitivity Tests
Plasmodium falciparum / drug effects
Pseudomonas aeruginosa / drug effects
Quaternary Ammonium Compounds / chemical synthesis
Quaternary Ammonium Compounds / chemistry
Quaternary Ammonium Compounds / pharmacology*
Rats
Salts / chemical synthesis
Salts / chemistry
Salts / pharmacology
Staphylococcus aureus / drug effects
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antifungal Agents
Antimalarials
Antineoplastic Agents
Quaternary Ammonium Compounds
Salts