PMID- 32683179
OWN - NLM
STAT- MEDLINE
DCOM- 20210318
LR  - 20210318
IS  - 1090-2120 (Electronic)
IS  - 0045-2068 (Linking)
VI  - 102
DP  - 2020 Sep
TI  - Asymmetric trisalkylamine cyclopropenium derivatives with antimicrobial activity.
PG  - 104069
LID - S0045-2068(20)31366-3 [pii]
LID - 10.1016/j.bioorg.2020.104069 [doi]
AB  - Cationic molecules are found in abundance as antimicrobial agents with a 
      well-defined mechanism of action and significant therapeutic benefits. Quaternary 
      ammonium-containing compounds are frequently employed due to their facile 
      synthesis and tunable properties. Over time, however, bacterial resistance to 
      these compounds has become a significant obstacle. We report here a series of 
      asymmetric trisalkylamine cyclopropenium cationic derivatives as chemical 
      isosteres of quaternary ammonium compounds, capable of strong antimicrobial 
      activity and overcoming microbial resistance. These small molecules were prepared 
      by one-pot reaction of tetrachlorocyclopropene (TCC) with unhindered secondary 
      amines in the presence of Hunig's base. In this work we describe the synthesis, 
      purification, and characterization of five trisamino-cyclopropenium derivatives 
      and confirm their structures by spectral analysis and mass-spectrometry. Three of 
      the compounds displayed considerable antimalarial activity (IC(50) < 0.1 microM) 
      without demonstrating significant toxic effects in vitro (TC(50) > 1 microM). This 
      class of cyclopropenium-based compounds provides an opening for the discovery of 
      potent and non-toxic antimicrobial agents.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Belay, Chen
AU  - Belay C
AD  - Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew 
      University of Jerusalem, Jerusalem 91120, Israel.
FAU - Steinman, Noam Y
AU  - Steinman NY
AD  - Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew 
      University of Jerusalem, Jerusalem 91120, Israel.
FAU - Campos, Luis M
AU  - Campos LM
AD  - Department of Chemistry, Columbia University, New York, NY 10027, USA.
FAU - Dzikowski, Ron
AU  - Dzikowski R
AD  - Department of Microbiology and Molecular Genetics, The Kuvin Centre for the Study 
      of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Golenser, Jacob
AU  - Golenser J
AD  - Department of Microbiology and Molecular Genetics, The Kuvin Centre for the Study 
      of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Domb, Abraham J
AU  - Domb AJ
AD  - Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew 
      University of Jerusalem, Jerusalem 91120, Israel. Electronic address: 
      avid@ekmd.huji.ac.il.
LA  - eng
PT  - Journal Article
DEP - 20200703
PL  - United States
TA  - Bioorg Chem
JT  - Bioorganic chemistry
JID - 1303703
RN  - 0 (Amines)
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Cations)
RN  - 0 (Cyclopropanes)
RN  - 7B8994OHJ0 (cyclopropene)
SB  - IM
MH  - Amines/chemical synthesis/chemistry/*pharmacology
MH  - Anti-Infective Agents/chemical synthesis/chemistry/*pharmacology
MH  - Cations/chemical synthesis/chemistry/pharmacology
MH  - Cell Line
MH  - Cyclopropanes/chemical synthesis/chemistry/*pharmacology
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Malaria/drug therapy/parasitology
MH  - Plasmodium falciparum/*drug effects
MH  - Staphylococcus epidermidis/drug effects
OTO - NOTNLM
OT  - Antimalarial
OT  - Cyclopropenium
OT  - Quaternary ammonium
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/07/20 06:00
MHDA- 2021/03/19 06:00
CRDT- 2020/07/20 06:00
PHST- 2020/05/04 00:00 [received]
PHST- 2020/06/28 00:00 [revised]
PHST- 2020/06/29 00:00 [accepted]
PHST- 2020/07/20 06:00 [pubmed]
PHST- 2021/03/19 06:00 [medline]
PHST- 2020/07/20 06:00 [entrez]
AID - S0045-2068(20)31366-3 [pii]
AID - 10.1016/j.bioorg.2020.104069 [doi]
PST - ppublish
SO  - Bioorg Chem. 2020 Sep;102:104069. doi: 10.1016/j.bioorg.2020.104069. Epub 2020 
      Jul 3.