2. Academic Validation
  3. Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action

Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action

  • Bioorg Med Chem Lett. 2020 Jul 1;30(13):127234. doi: 10.1016/j.bmcl.2020.127234.
Natalia V Terekhova 1,  Dmitry A Tatarinov 2,  Zukhra M Shaihutdinova 3,  Tatiana N Pashirova 1,  Anna P Lyubina 1,  Alexandra D Voloshina 1,  Anastasiia S Sapunova 1,  Lucia Ya Zakharova 1,  Vladimir F Mironov 1
Affiliations

Affiliations

  • 1 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation.
  • 2 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation. Electronic address: [email protected].
  • 3 Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russian Federation.
PMID: 32386856 DOI: 10.1016/j.bmcl.2020.127234
Abstract

Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1-2 μM) and fungi Tm and CA, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M-Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent Apoptosis.

Keywords

Antimicrobial activity; Critical micelle concentration; Cyclization; Cytofluorimetry; Cytotoxicity; Grignard reagents; Phosphine oxides; Phosphonium salts.

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