Stimulus-sensitive liposomal delivery system based on new 3,7-diazabicyclo[3.3.1]nonane derivatives

Polina N Veremeeva; Olga V Zaborova; Irina V Grishina; Dmitriy V Makeev; Vadim A Timoshenko; Vladimir A Palyulin

doi:10.1016/j.bmcl.2021.127871

Stimulus-sensitive liposomal delivery system based on new 3,7-diazabicyclo[3.3.1]nonane derivatives

Bioorg Med Chem Lett. 2021 May 1:39:127871. doi: 10.1016/j.bmcl.2021.127871. Epub 2021 Mar 2.

Authors

Polina N Veremeeva¹, Olga V Zaborova², Irina V Grishina², Dmitriy V Makeev², Vadim A Timoshenko², Vladimir A Palyulin³

Affiliations

¹ Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gory, 1-3, Russia. Electronic address: veremeeva@qsar.chem.msu.ru.
² Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gory, 1-3, Russia.
³ Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gory, 1-3, Russia; Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Severny pr., 1, Russia. Electronic address: vap@qsar.chem.msu.ru.

PMID: 33662539
DOI: 10.1016/j.bmcl.2021.127871

Abstract

3,7-Diazabicyclo[3.3.1]nonane scaffold can serve as a basis for the design of molecular switches stimulating the fast release of water soluble compounds under the influence of external factors from the liposomal containers having those switches incorporated into the lipid bilayer. It was demonstrated that liposomes having 3,7-dihexadecyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (3) incorporated into the liposomal membrane sharply increase the permeability upon pH decrease from 7.4 to 6.5, and compound 3 can serve as a pH-sensitive agent in the bilayer of liposomal nanocontainers. Similar but less pronounced effect was shown for liposomes modified with 3,7-bis(methyldodecylaminoacetyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane (5) and 3,7-didodecylsulfonyl-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-one (4). The structure (morphology) and size of modified liposomes were studied with scanned transmission electron microscopy.

Keywords: Bispidinones: 3,7-diazabicyclo[3.3.1]nonan-9-ones; Conformational reorganization; Molecular switches; Stimulus-sensitive liposomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aza Compounds / chemical synthesis
Aza Compounds / chemistry*
Lipid Bilayers / chemistry
Liposomes / chemistry
Microscopy, Electron, Transmission
Molecular Structure

Substances

Aza Compounds
Lipid Bilayers
Liposomes
3,7-diazabicyclo(3.3.1)nonane