Effect on AMPA receptors and lipophilicity of substituted pyridoindoles as potential neuroprotectors
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The effect of the chemical nature of substituents (–H, –CH3–, –OCH3, –F and –Cl) introduced into the tricyclic fragment of hydrogenated pyrido[4,3-b]indoles on the compounds ability to positively modulate the activity of ionotropic glutamate AMPA receptors have been studied. The unsubstituted derivative, compounds with a methyl group and a fluorine atom were found to have the highest bioactivity in this test. The partition coefficients of the synthesized derivatives in the system 1-octanol/buffer pH 7.4 in the temperature range of 293.15–313.15 K have been measured. It has been found that as the lipophilicity of the compounds studied increases, the maximum biological activity is achieved at a higher concentration of the administered substance. The thermodynamic transfer functions of the studied substances from aqueous medium to organic phase have been calculated.
KeywordsDerivatives of Dimebon Bioactivity 1-Octanol/buffer pH 7.4 system Partition coefficient Transfer thermodynamics
This work was supported by the grant of RFBR no. 18-43-370016.
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The authors report that there are no conflicts of interest in this article.
- Albert A (2012) Selective toxicity: the physico-chemical basis of therapy. Springer, New YorkGoogle Scholar
- Doody RS, Gavrilova SI, Sano M et al (2008) Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet 372:207–215. https://doi.org/10.1016/S0140-6736(08)61074-0 CrossRefGoogle Scholar
- Ghose AK, Viswanadhan VN, Wendoloski JJ (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1:55–68. https://doi.org/10.1021/cc9800071 CrossRefGoogle Scholar
- Hansch C (1971) Quantitative structure–activity relationship in drug design. In: Ariens EJ (ed) Drug design. Academic Press, New York, pp 271–342Google Scholar
- Hung DT, Protter AA, Jain RP et al (2015) Tetracyclic compounds, Patent US8999978 B2Google Scholar
- Kerns E, Li D (2008) Drug like properties: concepts, structure design and methods. Academic Press, New YorkGoogle Scholar
- Molleman A (2003) Patch clamping: an introductory guide to patch clamp electrophysiology. Wiley, ChichesterGoogle Scholar
- Thomas G (2000) Medicinal chemistry an introduction. Wiley, West SussexGoogle Scholar