Synthesis of amphiphilic seleninic acid derivatives with considerable activity against cellular membranes and certain pathogenic microbes.
Selenium compounds play a major role in Biology, where they are often associated with pronounced antioxidant activity or toxicity. Whilst most selenium compounds are not necessarily hazardous, their often selective cytotoxicity is interesting from a biochemical and pharmaceutical perspective. We have synthesized a series of amphiphilic molecules which combine a hydrophilic seleninic acid head group - which at the same time serves as thiol-specific warhead - with a hydrophobic tail. These molecules possess a surface activity similar to the one of SDS, yet their biological activity seems to exceed by far the one of a simple surfactant (e.g. SDS) or seleninic acid (e.g. phenyl seleninic acid). Such compounds effectively haemolyse Red Blood Cells and exhibit pronounced activity against Saccharomyces cerevisiae. From a chemical perspective, the seleninic warheads are likely to attack crucial cysteine proteins of the cellular thiolstat.
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
Peng
P
Du
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
Uma M
UM
Viswanathan
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, SRSMC UMR 7565, Université de Lorraine, 1 Boulevard Arago, 57070 Metz, France.
Zhanjie
Z
Xu
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany; Department of Food Hygiene, Faculty of Veterinary Medicine, Shahid Bahonar University, Kerman, Iran.
Hadi
H
Ebrahimnejad
Division of Biophysics, Department of Biology, Saarland University, D-66123 Saarbruecken, Germany.
Benjamin
B
Hanf
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
Torsten
T
Burkholz
Division of Pharmaceutics and Biopharmacy, Philipps University, D-35037 Marburg, Germany.
Marc
M
Schneider
Division of Biophysics, Department of Biology, Saarland University, D-66123 Saarbruecken, Germany.
Ingolf
I
Bernhardt
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, SRSMC UMR 7565, Université de Lorraine, 1 Boulevard Arago, 57070 Metz, France.
Gilbert
G
Kirsch
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany. Electronic address: c.jacob@mx.uni-saarland.de.
Claus
C
Jacob
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D003545:Cysteine / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects; D005658:Fungi / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008823:Micelles; D008826:Microbial Sensitivity Tests; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D018036:Selenium Compounds / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000935:Antifungal Agents; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D008823:Micelles; D016566:Organoselenium Compounds; D018036:Selenium Compounds; D013438:Sulfhydryl Compounds; C473453:seleninic acid; C442270:selenol; D003545:Cysteine; C025698:selenium disulfide
Amphiphile; Cytotoxic activity; Micelle; Seleninic acid; Thiolstat