sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20240116sibmed-1399Research ArticleОБЗОРЫREVIEWSНовые производные хиназолинона как объект при поиске веществ, проявляющих мультитаргетный эффектNew derivatives of quinazolinone as an object in the search for substances that exhibit a multi-target effecthttps://orcid.org/0000-0002-5210-5248СтариковаА. А.StarikovaA. A.

Старикова Алла Андреевна 

414000, г. Астрахань, ул. Бакинская, 121

Alla A. Starikova 

alhimik.83@mail.ruhttps://orcid.org/0000-0002-9994-4751ЦибизоваА. А.TsibizovaA. A.

Цибизова Александра Александровна, к.фарм.н. 

414000, г. Астрахань, ул. Бакинская, 121

Alexandra A. Tsibizova, candidate of pharmaceutical science 

414000, Astrakhan, Bakinskaya st., 121

sasha3633@yandex.ruhttps://orcid.org/0000-0002-8788-1511ЗолотареваН. В.ZolotarevaN. V.

Золотарева Наталья Валерьевна, к.т.н. 

414056, г. Астрахань, ул. Татищева, 20а 

Natalia V. Zolotareva, candidate of technical sciences 

414056, Astrakhan, Tatishcheva st., 20a

zoloto.chem@mail.ruhttps://orcid.org/0000-0002-9848-7149МережкинаД. В.MerezhkinaD. V.

Мережкина Дарья Владимировна 

400131, г. Волгоград, пл. Павших борцов, 1

Darya V. Merezhkina 

400066, Volgograd, Pavshikh Bortsov sq., 1

merezhkinad@mail.ruhttps://orcid.org/0000-0002-4721-0959ОзеровА. А.OzerovA. A.

Озеров Александр Александрович, д.х.н., проф. 

400131, г. Волгоград, пл. Павших борцов, 1

Alexandr A. Ozerov, doctor of chemical sciences, professor 

400066, Volgograd, Pavshikh Bortsov sq., 1

prof_ozerov@yahoo.comhttps://orcid.org/0000-0001-5336-4455СамотруеваМ. А.SamotruevaM. A.

Самотруева Марина Александровна, д.м.н., проф. 

414000, г. Астрахань, ул. Бакинская, 121

Marina A. Samotrueva, doctor of medical sciences, professor 

414000, Astrakhan, Bakinskaya st., 121

ms1506@mail.ruАстраханский государственный медицинский университет Минздрава РоссииРоссияAstrakhan State Medical University of Minzdrav of RussiaRussian FederationАстраханский государственный университет им. В.Н. ТатищеваРоссияTatishchev Astrakhan State UniversityRussian FederationВолгоградский государственный медицинский университет Минздрава РоссииРоссияVolgograd State Medical University of Minzdrav of RussiaRussian Federation202407032024441155171Copyright © Старикова А.А., Цибизова А.А., Золотарева Н.В., Мережкина Д.В., Озеров А.А., Самотруева М.А., 20242024Старикова А.А., Цибизова А.А., Золотарева Н.В., Мережкина Д.В., Озеров А.А., Самотруева М.А.Starikova A.A., Tsibizova A.A., Zolotareva N.V., Merezhkina D.V., Ozerov A.A., Samotrueva M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/1399

В силу стремительного роста числа болеющих диабетом в условиях осложненной эпидемиологической картины вопрос возможности воздействия фармакологических веществ на несколько мишеней приобретает большую значимость. Наиболее частыми инфекционными заболеваниями у больных сахарным диабетом являются инфекции дыхательных и мочевыводящих путей, кожи и мягких тканей, диабетические язвы стопы, отиты и пародонтальные инфекции. Противомикробные средства могут оказывать как прямое, так и непрямое гипогликемическое действие. Хиназолиноны, относящиеся к группе гетероциклических производных, проявляют широкий спектр фармакологической активности. Использование программы PASS с целью компьютерного прогнозирования фармакологической активности новых соединений показало высокую вероятность проявления гипогликемического эффекта производных хиназолинона. Полученные результаты мотивировали авторов на поиск взаимосвязи антимикробного и сахароснижающего эффектов в рамках общего направления изучения мультитаргетности лигандов лекарственных веществ. Анализ литературных данных, а также результатов собственных исследований фармакологической активности новых производных хиназолинона дает возможность разделить все лиганды на функциональные группы, обусловливающие дополнительное связывание с молекулой-мишенью. Хиназолиноновый фрагмент, характеризуясь уникальностью строения, может быть обоснованно отнесен к мультитаргетным лигандам. Триазольный цикл и сульфониламидная группа также могут целенаправленно связываться с молекулой-мишенью. Карбамидный остаток, фрагмент сульфонилмочевины и ацетамидная группа в зависимости от строения вещества могут функционировать и как специфический лиганд, и как функциональная группа, участвующая в стабилизации промежуточного переходного состояния. Результаты, полученные авторами и другими исследователями, позволяют сформулировать предположение о взаимосвязи механизмов антимикробной и гипергликемической активности.

Due to the rapid growth in the number of patients with diabetes in a complicated epidemiological picture, the question of the possibility of exposure of a substance to several targets becomes more important. It is noted that the most common infectious diseases in patients with diabetes mellitus are infections of the respiratory and urinary tract, skin and soft tissues, diabetic foot ulcers, otitis media and periodontal infections. Antimicrobial agents can have both direct and indirect hypoglycemic effects. Quinazolinones belonging to the group of heterocyclic derivatives exhibit a wide range of pharmacological activity. The use of the PASS program for the purpose of computer prediction of pharmacological activity showed a high probability of the hypoglycemic effect of new derivatives. The obtained results motivated the authors to search for the relationship between antimicrobial action and hypoglycemic effect within the general direction of studying the multi-targeting of drug ligands. Analysis of the literature data, as well as own studies of new quinazolinone derivative pharmacological activity make it possible to divide all ligands into functional groups that cause additional binding to the target molecule. The quinazolinone fragment, characterized by the uniqueness of its structure, can be reasonably attributed to multi-target ligands. The triazole cycle and the sulfonamide group can also purposefully bind to the target molecule. A carbamide residue, a fragment of sulfonylurea and an acetamide group, depending on the structure of the substance they are part of, can function both as a specific ligand and as a functional group involved in the stabilization of the intermediate transition state. The results obtained by the authors, as well as other researchers, allow us to formulate an assumption about the relationship between the mechanisms of antimicrobial and hyperglycemic activity.

противомикробная активностьгипогликемическое действиехиназолиноныкомпьютерное моделированиемультитаргетные лигандыantimicrobial activityhypoglycemic effectquinazolinonescomputer modelingmultitargeted ligandsИсследование выполнено в рамках государственного задания Министерства здравоохранения РФ в части проведения НИР по теме «Поиск и разработка перспективных соединений с антибактериальной активностью среди производных пиримидина для создания лекарственных препаратов» 48.2-2021.ReferencesMonte C.D., Bizzarri B., Gidaro M.C., Carradori S., Mollica A., Luisi G., Granese A., Alcaro S., Costa G., Basilico N., … Sisto F. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J. Enzyme Inhib. Med. Chem. 2015;30(6):1027–1033. doi: 10.3109/14756366.2014.1001755Monte C.D., Bizzarri B., Gidaro M.C., Carradori S., Mollica A., Luisi G., Granese A., Alcaro S., Costa G., Basilico N., … Sisto F. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J. Enzyme Inhib. Med. Chem. 2015;30(6):1027–1033. doi: 10.3109/14756366.2014.1001755Васильев П.М., Косолапов В.А., Спасов А.А., Яналиева Л.Р. Полифункциональные мультитаргетные лекарственные средства как основа фармакологии 21 века. Вестн. Волгогр. гос. ун-та. Сер. 11. Естеств. науки. 2018;8(1):36–39. doi: 10.15688/jvolsu11.2018.1.6Vasilev P.M., Kosolapov V.A., Spasov A.A., Yanalieva L.R. Multifunctional multitarget drugs as the basis of pharmacology of the 21st century. Vestnik Volgogradskogo gosudarstvennogo universiteta. Seriya 11. Estestvennye nauki = Science Journal of Volgograd State University. Natural Sciences. 2018;8(1):36–39. [In Russian]. doi: 10.15688/jvolsu11.2018.1.6Gray D.A., Wenzel M. Multi-purpose approaches to the fight against multi-resistant superbugs. ACS Infect. Dis. 2020;6(6):1346–1365. doi: 10.1021/acsinfecdis.0c00001Gray D.A., Wenzel M. Multi-purpose approaches to the fight against multi-resistant superbugs. ACS Infect. Dis. 2020;6(6):1346–1365. doi: 10.1021/acsinfecdis.0c00001Suresha G.P., Suhas R., Kapfo W., Gowda D.C. Urea/thiourea derivatives of quinazolinone-lysine conjugates: Synthesis and structure-activity relationships of a new series of antimicrobials. Eur. J. Med. Chem. 2011;46(6):2530–2540. doi: 10.1016/j.ejmech.2011.03.041Suresha G.P., Suhas R., Kapfo W., Gowda D.C. Urea/thiourea derivatives of quinazolinone-lysine conjugates: Synthesis and structure-activity relationships of a new series of antimicrobials. Eur. J. Med. Chem. 2011;46(6):2530–2540. doi: 10.1016/j.ejmech.2011.03.041Shannon C.E., Daniele G., Galindo C., Abdul-Ghani M.A., DeFronzo R.A., Norton L. Pioglitazone inhibits mitochondrial pyruvate metabolism and glucose production in hepatocytes. FEBS J. 2017;284(3):451–465. doi: 10.1111/febs.13992Shannon C.E., Daniele G., Galindo C., Abdul-Ghani M.A., DeFronzo R.A., Norton L. Pioglitazone inhibits mitochondrial pyruvate metabolism and glucose production in hepatocytes. FEBS J. 2017;284(3):451–465. doi: 10.1111/febs.13992Hegazy W.A.H., Rajab A.A.H., Abu Lila A.S., Abbas H.A. Anti-diabetics and antimicrobials: Harmony of mutual interplay. World J. Diabetes. 2021;12(11):1832–1855. doi: 10.4239/wjd.v12.i11.1832Hegazy W.A.H., Rajab A.A.H., Abu Lila A.S., Abbas H.A. Anti-diabetics and antimicrobials: Harmony of mutual interplay. World J. Diabetes. 2021;12(11):1832–1855. doi: 10.4239/wjd.v12.i11.1832Auti P.S., George G., Paul A.T. Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids. RSC Adv. 2020;10(68):41353–41392. doi: 10.1039/d0ra06642gAuti P.S., George G., Paul A.T. Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids. RSC Adv. 2020;10(68):41353–41392. doi: 10.1039/d0ra06642gGhaly H., Kriete C., Sahin S., Pfloger A., Holzgrabe U., Zunkler B.J., Rustenbeck I. The insulinotropic effect of fluoroquinolones. Biochem. Pharmacol. 2009;77(6):1040–1052. doi: 10.1016/j.bcp.2008.11.019Ghaly H., Kriete C., Sahin S., Pfloger A., Holzgrabe U., Zunkler B.J., Rustenbeck I. The insulinotropic effect of fluoroquinolones. Biochem. Pharmacol. 2009;77(6):1040–1052. doi: 10.1016/j.bcp.2008.11.019Ahmed O.M., Hussein A.M., Ahmed R.R. Antidiabetic and antioxidant effects of newly synthesized pyrimido[1,6-a]pyrimidine derivatives in neonatal streptozotocin-induced diabetic rats. Med. Сhem. 2012;2(1):020–028. doi: 10.4172/2161-0444.1000108Ahmed O.M., Hussein A.M., Ahmed R.R. Antidiabetic and antioxidant effects of newly synthesized pyrimido[1,6-a]pyrimidine derivatives in neonatal streptozotocin-induced diabetic rats. Med. Сhem. 2012;2(1):020–028. doi: 10.4172/2161-0444.1000108Noser A.A., Abdelmonsef A.H., El-Naggar M., Salem M.M. New amino acid Schiff bases as anticancer agents via potential mitochondrial complex Iassociated hexokinase inhibition and targeting AMPprotein kinases/mTOR signaling pathway. Molecules. 2021;26(17):5332. doi: 10.3390/molecules26175332Noser A.A., Abdelmonsef A.H., El-Naggar M., Salem M.M. New amino acid Schiff bases as anticancer agents via potential mitochondrial complex Iassociated hexokinase inhibition and targeting AMPprotein kinases/mTOR signaling pathway. Molecules. 2021;26(17):5332. doi: 10.3390/molecules26175332Kussmaul L., Hirst J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl. Acad. Sci. USA. 2006;103(20):7607–7612. doi: 10.1073_pnas.0510977103Kussmaul L., Hirst J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl. Acad. Sci. USA. 2006;103(20):7607–7612. doi: 10.1073_pnas.0510977103Masadeh M.M., Mhaidat N.M., Al-Azzam S.I., Alzoubi K.H. Investigation of the antibacterial activity of pioglitazone. Drug Des. Devel. Ther. 2011;5:421–425. doi: 10.2147/DDDT.S24126Masadeh M.M., Mhaidat N.M., Al-Azzam S.I., Alzoubi K.H. Investigation of the antibacterial activity of pioglitazone. Drug Des. Devel. Ther. 2011;5:421–425. doi: 10.2147/DDDT.S24126Pasquale T.R., Tan J.S. Nonantimicrobial effects of antibacterial agents. Clin. Infect. Dis. 2005;40(1):127–135. doi: 10.1086/426545Pasquale T.R., Tan J.S. Nonantimicrobial effects of antibacterial agents. Clin. Infect. Dis. 2005;40(1):127–135. doi: 10.1086/426545Dutta A., Trivedi P., Gehlot P.S., Gogoi D., Hazarika R., Chetia P., Kumar A., Chaliha A.K., Chaturvedi V., Sarma D. Development and synthesis of hybrids of quinazolinone and triazole as powerful anti-tuberculosis agents. ACS Appl. Bio. Mater. 2022;5(9):4413–4424. doi: 10.1021/acsabm.2c00562Dutta A., Trivedi P., Gehlot P.S., Gogoi D., Hazarika R., Chetia P., Kumar A., Chaliha A.K., Chaturvedi V., Sarma D. Development and synthesis of hybrids of quinazolinone and triazole as powerful anti-tuberculosis agents. ACS Appl. Bio. Mater. 2022;5(9):4413–4424. doi: 10.1021/acsabm.2c00562Hassanzadeh F., Sadeghi-Aliabadi H., Nikov S., Jafari E., Vasegi G. Synthesis and cytotoxic evaluation of some derivatives of triazolquinazolinone hybrids. Res. Pharm. Sci. 2019;14(2):130–137. doi: 10.4103/1735-5362.253360Hassanzadeh F., Sadeghi-Aliabadi H., Nikov S., Jafari E., Vasegi G. Synthesis and cytotoxic evaluation of some derivatives of triazolquinazolinone hybrids. Res. Pharm. Sci. 2019;14(2):130–137. doi: 10.4103/1735-5362.253360Saad H.A., Osman N.A., Mustafa A.H. Synthesis and analgesic activity of some new pyrazoles and triazoles containing a fragment of 6,8-dibromo-2-methylquinazoline. Molecules. 2011;16(12):10187–10201. doi: 10.3390/molecules161210187Saad H.A., Osman N.A., Mustafa A.H. Synthesis and analgesic activity of some new pyrazoles and triazoles containing a fragment of 6,8-dibromo-2-methylquinazoline. Molecules. 2011;16(12):10187–10201. doi: 10.3390/molecules161210187Kumar S., Hora S.L., Yadav A. Triazole analogues as potential pharmacological agents: a brief overview. Futur. J. Pharm. Sci. 2021;7(1):106. doi: 10.1186/s43094-021-00241-3Kumar S., Hora S.L., Yadav A. Triazole analogues as potential pharmacological agents: a brief overview. Futur. J. Pharm. Sci. 2021;7(1):106. doi: 10.1186/s43094-021-00241-3Baltaş N. Synthesis of quinazolinone derivatives containing an acyl hydrazone skeleton as potent anti-urease agents enzyme kinetic studies and anti-oxidant properties. J. Chem. Res. 2022;46(3):17475198221096568. doi: 10.1177/17475198221096568Baltaş N. Synthesis of quinazolinone derivatives containing an acyl hydrazone skeleton as potent anti-urease agents enzyme kinetic studies and anti-oxidant properties. J. Chem. Res. 2022;46(3):17475198221096568. doi: 10.1177/17475198221096568El-Hashash M.A., Rizk S.A., El-Bassiouny F.A. Reactivity of 2-ethoxyquinazolin- 4-yl hydrazine and its use in synthesis of novel quinazoline derivatives of antimicrobial activity. Glob. J. Health Sci. 2011;4(1):174–183. doi: 10.5539/gjhs.v4n1p174El-Hashash M.A., Rizk S.A., El-Bassiouny F.A. Reactivity of 2-ethoxyquinazolin- 4-yl hydrazine and its use in synthesis of novel quinazoline derivatives of antimicrobial activity. Glob. J. Health Sci. 2011;4(1):174–183. doi: 10.5539/gjhs.v4n1p174Kumar S., Hora S.L., Yadav A. Triazole analogues as potential pharmacological agents: a brief overview. Futur. J. Pharm. Sci. 2021;7(1):106. doi: 10.1186/s43094-021-00241-3Kumar S., Hora S.L., Yadav A. Triazole analogues as potential pharmacological agents: a brief overview. Futur. J. Pharm. Sci. 2021;7(1):106. doi: 10.1186/s43094-021-00241-3Старикова А.А., Габитова Н.М., Цибизова А.А., Озеров А.А., Тюренков И.Н., Башкина О.А., Самотруева М.А. Изучение антимикробной активности новых производных хиназолин-4(3Н)-она по отношению к Echerichia coli и Klebsiella pneumoniae. Астрах. мед. ж. 2022;17(1):60–71. doi: 10.48612/agmu/2022.17.1.60.71Starikova A.A., Gabitova N.M., Tsibizova A.A., Ozerov A.A., Tyurenkov I.N., Bashkina O.A., Samotrueva M.A. Study of antimicrobial activity of new quinazolin-4(3h)-one derivatives with respect to Echerichia coli and Klebsiella pneumoniae. Astrakhanskiy meditsinskiy zhurnal = Astrakhan Medical Journal. 2022;17(1):60–71. [In Russian]. doi: 10.48612/agmu/2022.17.1.60.71Rohde K.H., Sorci L. The prospective synergy of antitubercular drugs with NAD biosynthesis inhibitors. Frontiers in Microbiology. 2021;11:634640. doi: 10.3389/fmicb.2020.634640Rohde K.H., Sorci L. The prospective synergy of antitubercular drugs with NAD biosynthesis inhibitors. Frontiers in Microbiology. 2021;11:634640. doi: 10.3389/fmicb.2020.634640Боголюбова А.В., Майоров А.Ю., Мишина Е.Е., Шварц А.М., Белоусов П.В. Фарнезоидный рецептор (FXR) как потенциальная терапевтическая мишень при неалкогольной жировой болезни печени и ассоциированных заболеваниях. Сах. диабет. 2017;20(6):449–453. doi: 10.14341/DM9374Bogolyubova A.V., Mayorov A.Yu., Mishina E.E., Schwartz A.M., Belousov P.V. Farnesoid receptor (FXR) as a potential therapeutic target for non-alcoholic fatty liver disease and associated diseases. Sakharnyy diabet = Diabetes Mellitus. 2017;20(6):449–453. [In Russian]. doi: 10.14341/DM9374Hofmann A.F., Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proceedings of the National Academy of Sciences. 2006;103(12):4333–4334. doi: 10.1073/pnas.0600780103Hofmann A.F., Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proceedings of the National Academy of Sciences. 2006;103(12):4333–4334. doi: 10.1073/pnas.0600780103Bernstein C., Bernstein H., Payne C.M., Beard S.E., Schneider J. Activation of stress response promoters by bile salts in Escherichia coli. Curr. Microbiol. 1999;39(2):68–72. doi: 10.1007/s002849900420Bernstein C., Bernstein H., Payne C.M., Beard S.E., Schneider J. Activation of stress response promoters by bile salts in Escherichia coli. Curr. Microbiol. 1999;39(2):68–72. doi: 10.1007/s002849900420Tanassi D.G., Cheng L.V., Nikaido H. Active outflow of bile salts by E. coli. J. Bacteriol. 1997;179(8):2512–2518. doi: 10.1128/jb.179.8.2512-2518.1997Tanassi D.G., Cheng L.V., Nikaido H. Active outflow of bile salts by E. coli. J. Bacteriol. 1997;179(8):2512–2518. doi: 10.1128/jb.179.8.2512-2518.1997Gruden S., Poklar Ulrich N. Various mechanisms of antimicrobial activity of lactoferrins, lactoferricins and other peptides derived from lactoferrins. Int. J. Mol. Sci. 2021;22(20):11264.74. doi: 10.3390/ijms222011264Gruden S., Poklar Ulrich N. Various mechanisms of antimicrobial activity of lactoferrins, lactoferricins and other peptides derived from lactoferrins. Int. J. Mol. Sci. 2021;22(20):11264.74. doi: 10.3390/ijms222011264Vidal J.E., Wier M.N., Angulo-Zamudio U., McDevitt E., Jop Vidal A.G., Alibayov B., Scasny A., Wong S.M., Akerley B.J., McDaniel L.S. Prophylactic inhibition of colonization of Streptococcus pneumoniae by a secondary metabolite of bile acids with deoxycholic acid. Infect. Immun. 2021;16;89(12):e0046321. doi: 10.1128/iai.00463-21Vidal J.E., Wier M.N., Angulo-Zamudio U., McDevitt E., Jop Vidal A.G., Alibayov B., Scasny A., Wong S.M., Akerley B.J., McDaniel L.S. Prophylactic inhibition of colonization of Streptococcus pneumoniae by a secondary metabolite of bile acids with deoxycholic acid. Infect. Immun. 2021;16;89(12):e0046321. doi: 10.1128/iai.00463-21Garcia-Rubio R., de Oliveira H.K., Rivera J., Trevijano-Contador N. The cell wall of fungi: Candida, Cryptococcus and Aspergillus species. Front. Microbiol. 2020;10:2993. doi: 10.3389/fmicb.2019.02993Garcia-Rubio R., de Oliveira H.K., Rivera J., Trevijano-Contador N. The cell wall of fungi: Candida, Cryptococcus and Aspergillus species. Front. Microbiol. 2020;10:2993. doi: 10.3389/fmicb.2019.02993Temple M.J., Cuskin F., Baslé A., Hickey N., Speciale G., Williams S.J., Gilbert H.J., Lowe E.C. A Bacteroidetes locus dedicated to fungal 1,6- -glucan degradation: Unique substrate conformation drives specificity of the key endo-1,6-glucanase. J. Biol. Chem. 2017;292(25):10639–10650. doi: 10.1074/jbc.M117.787606Temple M.J., Cuskin F., Baslé A., Hickey N., Speciale G., Williams S.J., Gilbert H.J., Lowe E.C. A Bacteroidetes locus dedicated to fungal 1,6- -glucan degradation: Unique substrate conformation drives specificity of the key endo-1,6-glucanase. J. Biol. Chem. 2017;292(25):10639–10650. doi: 10.1074/jbc.M117.787606Li H., Kuzunis D., Cable M.A., de Vries R., Dilokpimol A. The glycoside hydrolase family 30 contains subfamilies of fungi with various polysaccharide properties. N. Biotechnol. 2022;67:32–41. doi: 10.1016/j.nbt.2021.12.004Li H., Kuzunis D., Cable M.A., de Vries R., Dilokpimol A. The glycoside hydrolase family 30 contains subfamilies of fungi with various polysaccharide properties. N. Biotechnol. 2022;67:32–41. doi: 10.1016/j.nbt.2021.12.004Chen J., Seviour R. Medicinal importance of fungal β-(1→3),(1→6)-glucans. Mycol. Res. 2007;111(6):635–652. doi: 10.1016/j.mycres.2007.02.011Chen J., Seviour R. Medicinal importance of fungal β-(1→3),(1→6)-glucans. Mycol. Res. 2007;111(6):635–652. doi: 10.1016/j.mycres.2007.02.011Camilli G., Tabure G., Quintin D. The complexity of fungal β-glucan in normal and in diseases: the effect on the system of mononuclear phagocytes. Front. Immunol. 2018;9:673. doi: 10.3389/fimmu.2018.00673Camilli G., Tabure G., Quintin D. The complexity of fungal β-glucan in normal and in diseases: the effect on the system of mononuclear phagocytes. Front. Immunol. 2018;9:673. doi: 10.3389/fimmu.2018.00673Jiezhong C., Kenneth R. Beta-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc. Health Risk Manag. 2008;4(6):1265–1272. doi: 10.2147/vhrm.s3803Jiezhong C., Kenneth R. Beta-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc. Health Risk Manag. 2008;4(6):1265–1272. doi: 10.2147/vhrm.s3803Cacciatore I., Cornacchia C., Pinnen F., Mollica A., di Stefano A. Prodrug approach for increasing cellular glutathione levels. Molecules. 2010;15(3):1242–1264. doi: 10.3390/molecules15031242Cacciatore I., Cornacchia C., Pinnen F., Mollica A., di Stefano A. Prodrug approach for increasing cellular glutathione levels. Molecules. 2010;15(3):1242–1264. doi: 10.3390/molecules15031242Aquilano K., Baldeli S., Cirillo M.R. Glutathione: a new role in the redox signaling of an old antioxidant. Front. Pharmacol. 2014;5:196. doi: 10.3389/fphar.2014.00196Aquilano K., Baldeli S., Cirillo M.R. Glutathione: a new role in the redox signaling of an old antioxidant. Front. Pharmacol. 2014;5:196. doi: 10.3389/fphar.2014.00196Chen N.H., Joko K.Y., Weirier F.J., McEwan A.G. Formaldehyde stress responses in bacterial pathogens. Front. Microbiol. 2016;7:257. doi: 10.3389/fmicb.2016.00257Chen N.H., Joko K.Y., Weirier F.J., McEwan A.G. Formaldehyde stress responses in bacterial pathogens. Front. Microbiol. 2016;7:257. doi: 10.3389/fmicb.2016.00257Umair S., Knight J.S., Bland R.J., Simpson H.V. Molecular and biochemical characterisation of arginine kinases in Haemonchus contortus and Teladorsagia circumcincta. Exp. Parasitol. 2013;134(3):362–367. doi: 10.1016/j.exppara.2013.03.011Umair S., Knight J.S., Bland R.J., Simpson H.V. Molecular and biochemical characterisation of arginine kinases in Haemonchus contortus and Teladorsagia circumcincta. Exp. Parasitol. 2013;134(3):362–367. doi: 10.1016/j.exppara.2013.03.011Palmer A., Regress B.N., van Houten D.M., Snyder M.J., Fraga D. Characterization of the putative oomycete taurocyamine kinase: significance for the evolution of the phosphagen kinase family. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 2013;166(3-4):173–181. doi: 10.1016/j.cbpb.2013.08.003Palmer A., Regress B.N., van Houten D.M., Snyder M.J., Fraga D. Characterization of the putative oomycete taurocyamine kinase: significance for the evolution of the phosphagen kinase family. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 2013;166(3-4):173–181. doi: 10.1016/j.cbpb.2013.08.003Yano D., Uda K., Nara M., Suzuki T. Diversity of phosphagen kinases in annelids: the first report on the sequences of a putative opheline kinase. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 2022;257:110662. doi: 10.1016/j.cbpb.2021.110662Yano D., Uda K., Nara M., Suzuki T. Diversity of phosphagen kinases in annelids: the first report on the sequences of a putative opheline kinase. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 2022;257:110662. doi: 10.1016/j.cbpb.2021.110662Terrossian E. der, Desvages G., Pradel L.A., Kassab R., Nguyen van T. Comparative structural studies of the active center of ATP: guanidine phosphotransferase: essential cysteine tryptic peptide of lombricine kinase from Lumbricus terrestris muscle. Eur. J. Biochem. 1971;22(4):585–592. doi: 10.1111/j.1432-1033.1971.tb01581.xTerrossian E. der, Desvages G., Pradel L.A., Kassab R., Nguyen van T. Comparative structural studies of the active center of ATP: guanidine phosphotransferase: essential cysteine tryptic peptide of lombricine kinase from Lumbricus terrestris muscle. Eur. J. Biochem. 1971;22(4):585–592. doi: 10.1111/j.1432-1033.1971.tb01581.xOgbonna E.K., Anderson H.R., Schmitz K.R. Identification of arginine phosphorylation in Mycobacterium smegmatis. Microbiol. Spectr. 2022;10(5):e0204222. doi: 10.1128/spectrum.02042-22Ogbonna E.K., Anderson H.R., Schmitz K.R. Identification of arginine phosphorylation in Mycobacterium smegmatis. Microbiol. Spectr. 2022;10(5):e0204222. doi: 10.1128/spectrum.02042-22Canonaco F. The relevance of transhydrogenases and heterologous phosphagen kinases for microbial cofactor metabolism: Doctoral dissertation, ETH Zurich. 2003.Canonaco F. The relevance of transhydrogenases and heterologous phosphagen kinases for microbial cofactor metabolism: Doctoral dissertation, ETH Zurich. 2003.Lopez-Marquez R.L., Theory L., Palmgren M.G., Pomorski T.G. P4-ATPases: lipid flippases in cell membranes. Pflugers. Arch. 2014;466(7):1227–1240. doi: 10.1007/s00424-013-1363-4Lopez-Marquez R.L., Theory L., Palmgren M.G., Pomorski T.G. P4-ATPases: lipid flippases in cell membranes. Pflugers. Arch. 2014;466(7):1227–1240. doi: 10.1007/s00424-013-1363-4Hoffman G.G. Octamer formation and stability in mitochondrial creatine kinase of protostomic invertebrates: Doctoral dissertation, Florida State University. 2005.Hoffman G.G. Octamer formation and stability in mitochondrial creatine kinase of protostomic invertebrates: Doctoral dissertation, Florida State University. 2005.Wu G. The important role of taurine, creatine, carnosine, anserin and 4-hydroxyproline in human nutrition and health. Amino Acids. 2020;52(3):329–360. doi: 10.1007/s00726-020-02823-6Wu G. The important role of taurine, creatine, carnosine, anserin and 4-hydroxyproline in human nutrition and health. Amino Acids. 2020;52(3):329–360. doi: 10.1007/s00726-020-02823-6Ruiz N. Lipid flippases for bacterial peptidoglycan biosynthesis. Lipid Insights.2015;8(s1):21–31. doi: 10.4137/Lpi.s31783Ruiz N. Lipid flippases for bacterial peptidoglycan biosynthesis. Lipid Insights.2015;8(s1):21–31. doi: 10.4137/Lpi.s31783Daleke D.L. Regulation of phospholipid asymmetry of the trans-bilayer plasma membrane. J. Lipid Res. 2003;44(2):233–242. doi: 10.1194/jlr.R200019-JLR200Daleke D.L. Regulation of phospholipid asymmetry of the trans-bilayer plasma membrane. J. Lipid Res. 2003;44(2):233–242. doi: 10.1194/jlr.R200019-JLR200Ansari I.U., Longacre M.J., Paulusma C.C., Stoker S.W., Kendrick M.A., MacDonald M.J. Characteristics of phospholipid translocases (flippases) of P4 ATPase in human and rat pancreatic beta cells: their gene suppression inhibits insulin secretion. J. Biol. Chem. 2015;290(38):23110–23123. doi: 10.1074/jbc.M115.655027Ansari I.U., Longacre M.J., Paulusma C.C., Stoker S.W., Kendrick M.A., MacDonald M.J. Characteristics of phospholipid translocases (flippases) of P4 ATPase in human and rat pancreatic beta cells: their gene suppression inhibits insulin secretion. J. Biol. Chem. 2015;290(38):23110–23123. doi: 10.1074/jbc.M115.655027Бондаренко О.Н., Галстян Г.Р., Анциферов М.Б., Кузнецова Т.В., Кобылянский А.Г. Биологическая роль оксида азота при сахарном диабете. Сахарный диабет. 2002;2:56–63.Bondarenko O.N., Galstyan G.R., Antsiferov M.B., Kuznetsova T.V., Kobylyansky A.G. The biological role of nitric oxide in diabetes mellitus. Sakharnyy diabet = Diabetes Mellitus. 2002;2:56–63. [In Russian].

The authors declare that there are no conflicts of interest present.