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• Markovic, B
• Dobricic, V
• Vladimirov, S
• Cudina, O
• Savic, V
• Karljikovic-Rajic, K
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• Markovic, B
• Dobricic, V
• Vladimirov, S
• Cudina, O
• Savic, V
• Karljikovic-Rajic, K
• [+] on PubMed
• Markovic, B
• Dobricic, V
• Vladimirov, S
• Cudina, O
• Savic, V
• Karljikovic-Rajic, K

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Molecules 2011, 16(3), 2658-2671; doi:10.3390/molecules16032658

Article

Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters—An In Vitro Model for Prodrug Activation

Bojan D. Markovic ^1,* , Vladimir D. Dobricic ¹ , Sote M. Vladimirov ¹ , Olivera A. Cudina ¹ , Vladimir M. Savic ²  and Katarina D. Karljikovic-Rajic ³

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia ² Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia ³ Department of Analytical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia

* Author to whom correspondence should be addressed.

Received: 18 January 2011; in revised form: 16 March 2011 / Accepted: 21 March 2011 / Published: 23 March 2011

(This article belongs to the Special Issue Prodrugs)

Download PDF Full-Text [370 KB, Updated Version, uploaded 24 March 2011 15:56 CET]

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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 NaHCO₃. 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 °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

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