Evaluation of molecular target of ademol by chemoinformatic method

Authors

  • S.I. Semenenko National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • A.I. Semenenko National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • R.G. Redkin V.N. Karazin Kharkiv National University, Kharkiv, Ukraine
  • I.F. Semenenko National Pirogov Memorial Medical University, Vinnytsia, Ukraine

DOI:

https://doi.org/10.22141/2224-0586.17.7.2021.244593

Keywords:

ademol, chemoinformatics, intracranial pressure, traumatic brain injury, blood-brain barrier

Abstract

Background. Glutamate excitotoxicity and intracranial hypertension are potential targets for possible developments of pathogenetic therapy of brain lesions, in particular those associated with high intracranial pressure. The purpose of the work: using chemoinformatic methods to justify the intravenous use of ademol, to detect the ability of ademol to block β-adrenergic receptors, as well as to assess the possibility of its passage through the blood-brain barrier in terms of drug-likeness and bioavailability criteria. Materials and methods. All calculations of molecular descriptors were made using the software package SIB Swiss Institute of Bioinformatics, computing platform and Molinspiration Cheminformatics v2016.09, available online. Results. The molecular weight of ademol does not exceed 500, the average lipophilicity value calculated using software package is in the acceptable range for the above compounds. For ademol, the value of LogP is 2,736, which is higher than that of rimantadine (2,456), but lower than that of propranolol (2,967). The total polar surface area is calculated based on the methodology developed by Ertl et al. in the form of contributions of the sum of the planes of O- and N-atoms etc., as a part of the functional groups of polar fragments. To predict ademol pe-netration through the blood-brain barrier, descriptors calculated in silico were used — average lipophilicity, which appeared to be close to previously described lipophilicity coefficient in a mixture of octanol and phosphate buffer, and the total polar surface area of mo-lecules. Affinity correlation (LogKi, nM) with polarity for known β-blockers and ademol is described as a second-degree parabolic polynomial function. Conclusions. A model of affinity correlation with lipophilicity for a number of β-blockers was created and the affinity of ademol is predicted, which is close to that of high-affi-nity non-selective β-blockers.

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References

Семененко С.І., Ходаківський О.А., Семененко О.М., Яковлева О.О., Семененко Н.О. Оцінка нейропротекторних властивостей Адемолу в умовах експериментальної черепно-мозкової травми. Вісник Вінницького національного університету ім. М.І. Пирогова. 2019. № 2. Т. 23. С. 109-212.

Mishra N.K., Kumar M., Raghava G.P. Support vector machine based prediction of glutathione S-transferase proteins. Protein Pept. Lett. 2007. Vol. 14(6). P. 575-580. Cited 13 times.

Nisoli E., Tonello C., Landi M., Carruba M.O. Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes. Mol. Pharmacol. 1996. Vol. 49(1). Р. 7-14.

Zhuravel' I.A., Kovalenko S.N., Ivashchenko A.V., Balakin K.V., Chernykh V.P., Skorenko A.V., Ivanenkov Ya.A. Zhurnal organichnoi ta farmatsevtichnoi khimii. Journal of organic and pharmaceutical chemistry. 2005. Vol. 3(1). P. 6-11.

Kaiser J.H., Flammer J., Scumfig D., Hendrickson P. Long term follow up of glaucoma patients treated with beta blockers. Surv. Ophthalmol. 1994. Vol. 38 (Suppl). S 156-S160.

Ertl P., Rohde B., Selzer P. Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties. J. Med. Chem. 2000. Vol. 43(20). P. 3714-3717.

Veber D.F., Johnson S.R., Cheng H.-Y., Smith B.R., Ward K.W., Kopple K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002. Vol. 45(12). P. 2615-2623.

Wei Wang, Hitoshi Sasaki, Du-Shieng Chien Z. and Vincent H.L. Lee. Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration. Current Eye Research. 1991. Vol. 10(6). Р. 571-579.

A simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J. Chem. Inf. Model. 2014. Vol. 54(12). Р. 3284-3301.

A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem. Med. Chem. 2016. М11(11). Р. 1117-1121.

Published

2021-11-25

How to Cite

Semenenko, S., Semenenko, A., Redkin, R., & Semenenko, I. (2021). Evaluation of molecular target of ademol by chemoinformatic method. EMERGENCY MEDICINE, 17(7), 37–41. https://doi.org/10.22141/2224-0586.17.7.2021.244593

Issue

Section

Original Researches