In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO(3). The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 degrees C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.
Keywords:
prodrug / fluocinolone acetonide esters / solvolysis / descriptor / in vitro model
TY - JOUR
AU - Marković, Bojan
AU - Dobričić, Vladimir
AU - Vladimirov, Sote
AU - Čudina, Olivera
AU - Savić, Vladimir
AU - Karljiković-Rajić, Katarina
PY - 2011
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1524
AB - In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO(3). The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 degrees C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.
PB - MDPI, Basel
T2 - Molecules
T1 - Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters-An In Vitro Model for Prodrug Activation
VL - 16
IS - 3
SP - 2658
EP - 2671
DO - 10.3390/molecules16032658
ER -
@article{
author = "Marković, Bojan and Dobričić, Vladimir and Vladimirov, Sote and Čudina, Olivera and Savić, Vladimir and Karljiković-Rajić, Katarina",
year = "2011",
abstract = "In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO(3). The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 degrees C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters-An In Vitro Model for Prodrug Activation",
volume = "16",
number = "3",
pages = "2658-2671",
doi = "10.3390/molecules16032658"
}
Marković, B., Dobričić, V., Vladimirov, S., Čudina, O., Savić, V.,& Karljiković-Rajić, K.. (2011). Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters-An In Vitro Model for Prodrug Activation. in Molecules
MDPI, Basel., 16(3), 2658-2671.
https://doi.org/10.3390/molecules16032658
Marković B, Dobričić V, Vladimirov S, Čudina O, Savić V, Karljiković-Rajić K. Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters-An In Vitro Model for Prodrug Activation. in Molecules. 2011;16(3):2658-2671.
doi:10.3390/molecules16032658 .
Marković, Bojan, Dobričić, Vladimir, Vladimirov, Sote, Čudina, Olivera, Savić, Vladimir, Karljiković-Rajić, Katarina, "Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters-An In Vitro Model for Prodrug Activation" in Molecules, 16, no. 3 (2011):2658-2671,
https://doi.org/10.3390/molecules16032658 . .
