Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 25, Art. 35 (pp. 630-647)    |    2024       

»

Violuriic acids: history, pharmacology and prospects (Analytical review)

Krasnov K.A., Krasnova A.A., Feklistova K.A., Papp V.T.

Federal State Budgetary Institution «Scientific and Clinical Center of Toxicology named after academician S.N. Golikov of the Federal Medical and Biological Agency

Brief summary

The development of drugs that enhance the adaptive capabilities of the body is one of the priorities of modern pharmacology. In this regard, 5-hydroxyiminobarbituric (violuric) acid and its derivatives are of interest - a group of heterocyclic substances of synthetic origin with antihypoxant, actoprotective, antioxidant, hepatoprotective, pulmonoprotective, antimicrobial and many other types of activity. By their structure, chemical and biological properties, violuric acids have no analogues among the known antihypoxants and actoprotectors, which makes them promising objects for the development of drugs with an original mechanism of action. The aim of the study. Systematization of the literature data on violuric acids and assessment of the prospects for using this group of compounds in the development of pharmacological agents to increase the adaptive capabilities of the body. Materials and methods/ Russian and foreign scientific publications identified as a result of the search were used as materials. logP values were evaluated using the ACD Labs 2016 software package. Outcomes. 5-Hydroxyiminobarbituric acids and their 2-thioanalogs, called violuric acids (VA), are a group of heterocyclic oximes. The structural basis of the group is 5-hydroxyminopyrimidine scaffold, which possess an acidic, redox and complexing properties. The biological properties of violuric acids are diverse and significantly depend on the nature of the substituents. 1-(4-Bromophenyl)violuric acid is approved for use as an official drug for the treatment of liver diseases. Unsubstituted violuric acid, 1,3-dimethylvioluric and 2-thiovioluric (TVA) acids are active as antihypoxants, exhibit adaptogenic properties and protect the body from poisoning with nitrites and aniline, and 2-methylthiovioluric acid has a therapeutic effect in toxic pulmonary edema. Substances with interferon-inducing, hepatoprotective neuroprotective, bacteriostatic and antiviral properties have been found in a number of N-substituted derivatives of VC and TVA. At the biochemical level, the action of violurates has a multifaceted character, the activation of the body's adaptation mechanisms, antioxidant and membrane stabilizing effects are particularly noted. Conclusion. The available data indicate the high biological value of violuric acids. Due to their potential for chemical and pharmacological diversity, derivatives of this group represent a promising area for pharmaceutical development. The main directions of development are the search for drugs with antihypoxant, adaptogenic, decongestant and cytoprotective effects.


Key words

5-(hydroxyimino)pyrimidine-2,4,6(1H,3H,5H)-trione, violuric acid, derivatives, 2-thioanalogs, pharmacological activity, antihypoxants, antidotes, adaptogens, hepatoprotectors, antioxidants

Reference list

1 Smirnov A.V., Krivorychko B.I. Antigipoksanti v neotlojnoi medicine. Anesteziologiya i reanimatologiya. 1998; 2: 50-55 .


2 Starokon P.M., Hanevich M.D. Antigipoksanti v hiryrgii: perspektivi razvitiya. Gospitalnaya medicina: nayka i praktika. 2022; 5(3): 56-62.


3 Oganov R.G. Polojitelnii opit primeneniya etilmetilgidroksipiridina sykcinata v lechenii kardiologicheskih bolnih. Kardiovaskylyarnaya terapiya i profilaktika. 2017; 16(5): 91-94 .


4 Shilov A.M. Antigipoksanti i antioksidanti v kardiologicheskoi praktike. Rysskii medicinskii jyrnal. 2004; 12(2): 112-114 .


5 Shamrei V.K., Kyrasov E.S., Nechiporenko V.V. i dr. Vozmojnosti primeneniya Meksidola v kompleksnoi terapii psihicheskih rasstroistv. Jyrnal nevrologii i psihiatrii im. S.S. Korsakova. 2020; 120(5): 160-164.


6 Golovko A.I., Batocirenova E.G., Komov U.V.i dr. Obzor lekarstvennih preparatov dlya korrekcii naryshenii CNS, razvivshihsya v rezyltate deistviya neirotoksikantov. Medline.ru. 2022; 23: 385-419.


7 Oliynyk S., Oh S. The pharmacology of actoprotectors: practical application for improvement of mental and physical performance. Biomolecules and Therapeutics. 2012; 20(5): 446-456.


8 Okovitii S.V., Syhanov D.S., Zaplytanov V.A. i dr. Antigipoksanti v sovremennoi klinicheskoi praktike. Klinicheskaya medicina. 2012; 90(9): 63-68.¬¬


9 Zarybina I.V., Shabanov P.D. Molekylyarnaya farmakologiya antigipoksantov. SPb : Izdatelstvo N-L; 2004.


10 Miheev V.V., Marisheva V.V., Shabanov P.D. Vliyanie amtizola na mejpolysharnyu asimmetriu golovnogo mozga mishei linii SHR pri giperkapnicheskoi gipoksii. Asimmetriya. 2011; 5(3): 23-34.


11 Lykyanova L.D. red. Metodicheskie rekomendacii po eksperimentalnomy izycheniu preparatov, predlagaemih dlya klinicheskogo izycheniya v kachestve antigipoksicheskih sredstv. M.: 1990.


12 Voronina T.A. Meksidol: spektr farmakologicheskih effektov. Jyrnal nevrologii i psihiatrii im. S.S. Korsakova. 2012; 112(12): 86-90.


13 Mashkovskii M. D. Lekarstvennie sredstva. 16-e izd. M.: Novaya volna; 2012.


14 Shilov A.M., Osiya A.O. Antigipoksanti i antioksidanti s metabolicheskim deistviem (trimetazidin) pri ishemicheskoi miokardiopatii. Rysskii medicinskii jyrnal. 2010; 10: 663-667.


15 Petr D.Sh., Zarubina I.V. Hypoxia and antihypoxants, focus on brain injury. Reviews on Clinical Pharmacology and Drug Therapy. 2019; 17(1): 7-16.


16 Marisheva V.V. Antigipoksanti aminotiolovogo ryada. Obzori po klinicheskoi farmakologii i lekarstvennoi terapii. 2007; 5(1): 17-28.


17 Repina E.F., Hysnytdinova N.U., Timasheva G.V. i dr. Morfologicheskie osobennosti gepatoprotektornogo deistviya antigipoksantov pri ostrom porajenii pecheni tetrahlormetanom v eksperimente. Toksikologicheskii vestnik. 2019; 1(154): 43-48.


18 Shystov E.B., Karkishenko V.N., Semenov H.H. i dr. Poisk zakonomernostei, opredelyaushih antigipoksicheskyu aktivnost soedinenii s nootropnim i neiroprotektornim deistviem. Biomedicina. 2015; 1: 18-23.


19 Baeyer A. Untersuchungen über die Harnsäuregruppe. Annalen der Chemie und Pharmacie. 1863; 127(2): 199-236.


20 Liebing P., Stein F., Hilfert L. et al. Synthesis and Structural Investigation of Brightly Colored Organoammonium Violurates. Zeitschrift für Anorganische und Allgemeine Chemie. 2019; 645: 36-43.


21 Biltz H., Sedlatscheck K. 5-Nitro-barbitursäuren. Chem. Ber. 1924; 57(2): 339-349.


22 Piloty O., Finckh K. Ueber die Harnsäuregruppe. Leib. Ann. 1904; 333(1): 22-71.


23 Clesarev V. I. Alkilirovanie i prototropnie prevrasheniya polifynkcionalnih oksipirimidinov. Avtoreferat diss. d.h.n. Sankt-Peterbyrg, 1992.


24 Bonacin J.A., A. Formiga L.B., de Melo V.H.S. et al. Vibrational spectra and theoretical studies of tautomerism and hydrogen bonding in the violuric acid and 6-amino-5-nitrosouracil system. Vibrational Spectroscopy. 2007; 44: 133-141.


25 Lipinski C.A., Lombardo F., Dominy B.W. et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 2001; 46(1-3): 3-26.


26 Teilor M.E., Robinson R.Dj. Ispolzovanie 1,3-dimetilviolyrovoi kisloti pri spektrofotometricheskom titrovanii shelochnih i shelochnozemelnih solei. Analiticheskaya himiya. 1962; 34(4): 533-536.


27 Muraca R.F. Photometric determination of sodium in blood serum with violuric acid. Chemist Analyst. 1955; 44: 38-42.


28 Bojarski J.T., Mokrosz J.L., Barton A.J. et al. Recent Progress in Barbituric Acid Chemistry. Advances in Heterocyclic Chemistry (Ed. by Katritzky A.R.). 1985; 38: 229-297.


29 Lorenz V., Liebing P., Engelhardt F. et al. Review: the multicolored coordination chemistry of violurate anions. Journal of Coordination Chemistry. 2019; 72 (1): 1-34.


30 Byrbello A.T. Proizvodnie barbityrovoi kisloti - novii klass soedinenii dlya profilaktiki i lecheniya otravlenii nitrosoedineniyami. Avtoreferat diss. d.m.n. Sankt-Peterbyrg, 1991.


31 Douros J., Kerst A. Use of violuric acid as a fungicide or bactericide. Patent US 3728461A.


32 Na H.C., Howard-Nordan K.S., Bush R.D. Toilet bowl cleaners containing urease inhibitors. Patent US WO 96/40856.


33 Ashkinazi R.I. N-Zameshennie proizvodnie 5-oksiiminobarbityrovoi kisloti: patent RF № 2188196.


34 Shygalei I.V., Celinskii I.V., Krasnov K.A. i dr. Ingibiryushee deistvie proizvodnih violyrovoi kisloti v reakcii okisleniya oksigemoglobina nitrit-ionom. Jyrnal obshei himii. 1993; 63(7): 1646-1650.


35 Krasnov K.A., Melihova M.V., Barinov V.A. Antidot okisi ygleroda: patent RF № 2581467.


36 Vakynenkova O.A., Krasnov K.A., Rojko M.A. i dr. Eksperimentalnoe obosnovanie poiska novih sredstv antidotnoi zashiti pri otravleniyah ygarnim gazom. V sbornike: Sbornik materialov IV Vserossiiskoi naychno-prakticheskoi konferencii «Aktyalnie problemi diagnostiki i lechenie professionalno obyslovlennih zabolevanii». Sochi; 2016: 47-48.


37 Gosydarstvennii reestr lekarstvennih sredstv. M.: Minzdrav Rossii, Fond farmacevticheskoi informacii; Registracionnoe ydostoverenie LP-004447 ot 01.09 2017. https://grls.pharm-portal.ru/grls/72353fc1-f30f-4ce6-87b0-085a5e8c4994#summary


38 Tec V.V., Tec G.V., Krasnov K.A. Lekarstvennoe sredstvo s gepatoprotektornoi aktivnostu: pat. 2595868 Ros. Federaciya: MPK A61K 31/513, A61P 1/16 (2006.01); № 2015111184/15


39 Kostrova T.A., Batocirenova E.G., Zolotoverhaya E.A. i dr. Vliyanie violyrovoi kisloti na antioksidantnyu sistemy v otdalennii period posle otravleniya tiopentalom natriya. Medline.ru. 2021; 22: 551-561.


40 Kolbasova T.A., Chalisova N.I., Egozova E.S. i dr. Ocenka effektivnosti cinkovogo kompleksa 1-bytilviolyrovoi kisloti dlya farmakologicheskoi korrekcii posledstvii citotoksicheskogo deistviya sydorojnih yadov. Toksikologicheskii vestnik. 2023; 31(1): 18-23.


41 Byrbello F.T., Denisenko P.P., Slesarev V.I. i dr. Natrievaya sol 2-metiltioviolyrovoi kisloti, proyavlyaushaya protivootechnyu aktivnost. Avt. svidetelstvo SSSR N 4774701; 1989.

Журнал основан 16 ноября 2000г.
Выдано Министерством РФ по делам печати, телерадиовещания и средств массовых коммуникаций

(c) Перепечатка материалов сайта Medline.Ru возможна только с письменного разрешения редакции