| Autor: |
Singh AK; Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India., Italiya KS; Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India., Narisepalli S; Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India., Chitkara D; Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India., Mittal A; Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2021 Oct 14; Vol. 64 (19), pp. 14217-14229. Date of Electronic Publication: 2021 Sep 28. |
| DOI: |
10.1021/acs.jmedchem.1c00391 |
| Abstrakt: |
Several drug-fatty acid (FA) prodrugs have been reported to exhibit desirable physicochemical and pharmacological profile; however, comparative beneficial effects rendered by different FAs have not been explored. In the present study, four different FAs (linoleic acid, oleic acid, palmitic acid, and α-lipoic acid) were selected based on their chain length and degree of unsaturation and conjugated to Lisofylline (LSF), an antidiabetic molecule to obtain different drug-FA prodrugs and characterized for molecular weight, hydrophobicity, purity, self-assembly, and efficacy in vitro and in vivo in type 1 diabetes model. Prodrugs demonstrated a 2- to 6-fold increase in the plasma half-life of LSF. Diabetic animals treated with prodrugs, once daily for 5 weeks, maintained a steady fasting blood glucose level with a significant increase in insulin level, considerable restoration of biochemical parameters, and preserved β-cells integrity. Among the different LSF-FA prodrugs, LSF-OA and LSF-PA demonstrated the most favorable physicochemical, systemic pharmacokinetic, and pharmacodynamic profiles. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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