TY - JOUR

T1 - Spin-Labeled Diclofenac: Synthesis and Interaction with Lipid Membranes

AU - Baranov, Denis S

AU - Kashnik, Anna S

AU - Atnyukova, Anastasiya N

AU - Dzuba, Sergei A

N1 - This work was supported by the Russian Science Foundation, project # 21-13-00025.

PY - 2023/8/10

Y1 - 2023/8/10

N2 - Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic properties. The interaction of non-steroidal anti-inflammatory drugs with cell membranes can affect their physicochemical properties, which, in turn, can cause a number of side effects in the use of these drugs. Electron paramagnetic resonance (EPR) spectroscopy could be used to study the interaction of diclofenac with a membrane, if its spin-labeled analogs existed. This paper describes the synthesis of spin-labeled diclofenac (diclofenac-SL), which consists of a simple sequence of transformations such as iodination, esterification, Sonogashira cross-coupling, oxidation and saponification. EPR spectra showed that diclofenac-SL binds to a lipid membrane composed of palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). 2H electron spin echo spectroscopy (ESEEM) was used to determine the position of the diclofenac-SL relative to the membrane surface. It was established that its average depth of immersion corresponds to the 5th position of the carbon atom in the lipid chain.

AB - Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic properties. The interaction of non-steroidal anti-inflammatory drugs with cell membranes can affect their physicochemical properties, which, in turn, can cause a number of side effects in the use of these drugs. Electron paramagnetic resonance (EPR) spectroscopy could be used to study the interaction of diclofenac with a membrane, if its spin-labeled analogs existed. This paper describes the synthesis of spin-labeled diclofenac (diclofenac-SL), which consists of a simple sequence of transformations such as iodination, esterification, Sonogashira cross-coupling, oxidation and saponification. EPR spectra showed that diclofenac-SL binds to a lipid membrane composed of palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). 2H electron spin echo spectroscopy (ESEEM) was used to determine the position of the diclofenac-SL relative to the membrane surface. It was established that its average depth of immersion corresponds to the 5th position of the carbon atom in the lipid chain.

KW - Diclofenac

KW - Spin Labels

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Membranes

KW - Glycerylphosphorylcholine

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85168742685&origin=inward&txGid=3cd0f58291b4ae164a46f2d64631d0e4

U2 - 10.3390/molecules28165991

DO - 10.3390/molecules28165991

M3 - Article

C2 - 37630243

VL - 28

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 16

M1 - 5991

ER -