Predictive analysis and prediction of the main molecular targets for the N-acetyl-6-aminohexanoate derivative

Антон П. Даниленко; Алексей А. Хентов; Алексей В. Кузнецов; Вероника С. Шмигерова; Юлия В. Степенко; Алла П. Тарасова; Владимир И. Якушев; Елизавета В. Боева; Альбина В. Миллер; Ирина А. Татаренкова; Татьяна В. Пузанова; Яна В. Лобода; Андрей П. Тращенко; Олег С. Гудырев; Анна Л. Мотайло; Владимир Н. Кузичкин; Валентина Н. Милашечко; Людмила М. Даниленко

doi:10.18413/rrpharmacology.11.560

Авторы

Антон П. Даниленко Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0001-2419-8109
Алексей А. Хентов Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0006-4315-0828
Алексей В. Кузнецов Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-1889-1297
Вероника С. Шмигерова Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-2941-0241
Юлия В. Степенко Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0002-7414-7326
Алла П. Тарасова Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0002-7296-0022
Владимир И. Якушев Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-3922-2359
Елизавета В. Боева Белгородский государственный национальный исследовательский университет
Альбина В. Миллер Belgorod State National Research University https://orcid.org/0000-0003-0162-9196
Ирина А. Татаренкова Курский государственный медицинский университет https://orcid.org/0000-0002-6477-1934
Татьяна В. Пузанова Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0003-7926-8447
Яна В. Лобода Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0004-0237-5233
Андрей П. Тращенко Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0004-5523-5779
Олег С. Гудырев Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-0097-000X
Анна Л. Мотайло Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0007-5118-5964
Владимир Н. Кузичкин Белгородский государственный национальный исследовательский университет
Валентина Н. Милашечко Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0003-9002-3985
Людмила М. Даниленко Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-6101-8712

DOI:

https://doi.org/10.18413/rrpharmacology.11.560

Аннотация

Introduction: N-acetyl-6-aminohexanoate (acexamic acid) and its derivatives are actively studied as promising compounds for the creation of new drugs, but their pharmacokinetic parameters and detailed mechanisms underlying a wide range of biochemical activities are still unclear.

Materials and Methods: PASS Online, Molinspiration Property Calculation Service and OSIRIS Property Explorer were used for predictive analysis. To determine the molecular biomarkers of the N-acetyl-6-aminohexanoate derivative – 2-ethyl-6-methyl-3-hydroxypyridinium N-acetylhexanoic acid, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were predicted. Molecular docking was performed using GalaxyWEB Sagittarius service followed by evaluation of the results using RCSB Protein Data Bank and UniProt Consortium databases.

Results: The study of the pharmacokinetic properties of 2-ethyl-6-methyl-3-hydroxypyridine N-acetyl-6-aminohexanoate revealed its potential suitability as a promising drug with high bioavailability. The highest degree of affinity is predicted with the eNOS center – binding energy from -7.2 to -8.3 kcal/mol; the VEGF center – binding energies from -6.1 to -7.7 kcal /mol, and the RANKL centre – binding energies from - 6.0 - 6,9 kcal mol.

Conclusion: The results of predictor analysis and molecular docking suggest that the N-acetyl-6-aminohexanoate-2-ethyl-6-methyl-3-hydroxypyridinium derivative is a safe and promising compound. Potential biotargets include eNOS, VEGF, and RANKL.

Графическая аннотация

Ключевые слова:

molecular docking, drug discovery, 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate, eNOS, VEGF, RANKL

Библиографические ссылки

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Вклад авторов

Антон П. Даниленко, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: 1190540@bsuedu.ru; ORCID ID: https://orcid.org/0009-0001-2419-8109. The author participated in the study design, conducted the experimental work, and analyzed the data.

Алексей А. Хентов, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; е-mail: alexeyhentov@gmail.com; ORCID ID: https://orcid.org/0009-0006-4315-0828. The author analyzed the results and participated in the experimental work.

Алексей В. Кузнецов, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: kav8080@bk.ru; ORCID ID:https://orcid.org/0000-0003-1889-1297. The author analyzed the results and participated in the experimental work.

Вероника С. Шмигерова, Белгородский государственный национальный исследовательский университет

Assistant Professor, Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: nika.beliaeva@yandex.ru; ORCID ID: https://orcid.org/0000-0003-2941-0241. The author took part in writing the article and processing the results obtained.

Юлия В. Степенко, Белгородский государственный национальный исследовательский университет

Assistant Professor, Assistant, Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: stepenko@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0002-7414-7326. The author took part in writing the article and processing the results obtained.

Алла П. Тарасова, Белгородский государственный национальный исследовательский университет

PhD in Medicine , Associate Professor, anesthesiologist resuscitator, St. Joasaph Belgorod Regional Clinical Hospital, Belgorod, Russia; e-mail: tarasova_ap@mail.ru; ORCID ID: https://orcid.org/0000-0002-7296-0022. The author analyzed the literature and participated in interpreting the data.

Владимир И. Якушев, Белгородский государственный национальный исследовательский университет

PhD in Medicine, Associate Professor, Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: vladiyakush@yandex.ru; ORCID ID: https://orcid.org/0000-0003-3922-2359. The author participated in the review and analysis of literature sources.

Елизавета В. Боева, Белгородский государственный национальный исследовательский университет

Undergraduate student, Medical Institute, Belgorod State National Research University, Belgorod, Russia; e-mail: liza.boeva31@gmail.com; ORCID ID: https://orcid.org/0000-0002-4802-172Х. The author took part in writing the article and processing the results obtained.

Альбина В. Миллер, Belgorod State National Research University

Undergraduate student, Medical Institute, Belgorod State National Research University, Belgorod, Russia; e-mail: cherednichenko.albina@gmail.com; ORCID ID: https://orcid.org/0000-0003-0162-9196. The author took part in writing the article and processing the results obtained.

Ирина А. Татаренкова, Курский государственный медицинский университет

Assistant Professor, Associate Professor of the Department of Pharmacology, Kursk State Medical University, Kursk, Russia; e-mail: irtalex@yandex.ru; ORCID ID: https://orcid.org/0000-0002-6477-1934. The author analyzed the literature and participated in interpreting the data.

Татьяна В. Пузанова, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: tatius_ktv@mail.ru; ORCID ID: https://orcid.org/0009-0003-7926-8447. The author participated in the article writing, analyzed the results and participated in the experimental work.

Яна В. Лобода, Белгородский государственный национальный исследовательский университет

MD, postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: loboda.yana0104@yandex.ru; ORCID ID: https://orcid.org/0009-0004-0237-5233. The author analyzed the results and participated in the experimental work.

Андрей П. Тращенко, Белгородский государственный национальный исследовательский университет

Undergraduate student, Institute of Medicine, Belgorod State National Research University, Belgorod, Russia; e-mail: 1698008@bsuedu.ru; ORCID ID: https://orcid.org/0009-0004-5523-5779. The author analyzed the literature and participated in interpreting the data.

Олег С. Гудырев, Белгородский государственный национальный исследовательский университет

Assistant Professor, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: gudyrev@mail.ru; ORCID ID: https://orcid.org/0000-0003-0097-000X. The author took part in writing the article, developing a research design, and processing the results obtained.

Анна Л. Мотайло, Белгородский государственный национальный исследовательский университет

Undergraduate student, Belgorod State National Research University, Belgorod, Russia; e-mail: 1468748@bsuedu.ru; ORCID ID: https://orcid.org/0009-0007-5118-5964. The author was engaged in conducting the literature analysis.

Владимир Н. Кузичкин, Белгородский государственный национальный исследовательский университет

Neurosurgeon, City Hospital No 2 of Belgorod, Belgorod, Russia; e-mail: kuzichkin_v@bsuedu.ru; ORCID ID: https://orcid.org/0000-0002-9012. The author analyzed the literature and participated in interpreting the data.

Валентина Н. Милашечко, Белгородский государственный национальный исследовательский университет

Undergraduate student, Medical Institute, Belgorod State National Research University, Belgorod, Russia; e-mail: 1463347@bsuedu.ru; ORCID ID: https://orcid.org/0009-0003-9002-3985. The author analyzed the literature and participated in interpreting the data obtained.

Людмила М. Даниленко, Белгородский государственный национальный исследовательский университет

Assistant Professor, Full Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: Danilenko_L@bsuedu.ru; ORCID ID: https://orcid.org/0000-0001-6101-8712. The author was engaged in collection and interpretation of the data for the paper.