Antihypoxic properties of condensed benzimidazole derivatives with antioxidant activity
- Authors: Spasov A.A.1, Kosolapov V.A.1, Anisimova V.A.2, Zhukovskaya O.N.2
-
Affiliations:
- Volgograd State Medical University
- Research Institute for Physical and Organic Chemistry, Southern Federal University
- Issue: Vol 17, No 1 (2019)
- Pages: 31-36
- Section: Original study articles
- URL: https://journal-vniispk.ru/RCF/article/view/12963
- DOI: https://doi.org/10.17816/RCF17131-36
- ID: 12963
Cite item
Full Text
Abstract
Hypoxia plays an important role in the vital activity of the organism and practically accompanies any pathology. Hypoxia and tissue ischemia in the early stages are accompanied by the activation of lipid peroxidation. Derivatives of 9-dialkylaminoethyl imidazobenzimidazole with a 3,4-dioxyphenyl substitute showed high antioxidant activity. Therefore, they have been studied for antihypoxic activity in experimental models of hypobaric, histotoxic and hemic hypoxia, as well as in animals pre-typed for resistance to hypoxia, and it was shown that new condensed benzimidazole derivatives with antioxidant activity showed a wide range of antihypoxic activity. The most pronounced protective antihypoxic properties were demonstrated by compound RU-185.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Alexander A. Spasov
Volgograd State Medical University
Author for correspondence.
Email: aspasov@mail.ru
Academician of the Russian Academy of Sciences, PhD, Professor. Head of the Department of Pharmacology and Bioinformatics
Russian Federation, VolgogradVadim A. Kosolapov
Volgograd State Medical University
Email: vad-ak@mail.ru
PhD, Professor of the Department of Pharmacology and Bioinformatics
Russian Federation, VolgogradVera A. Anisimova
Research Institute for Physical and Organic Chemistry, Southern Federal University
Email: anis39@mail.ru
PhD, Senior Researcher, Research Institute of Physical and Organic Chemistry
Russian Federation, Rostov-on-DonOlga N. Zhukovskaya
Research Institute for Physical and Organic Chemistry, Southern Federal University
Email: zhukowskaia.ol@yandex.ru
PhD, Senior Researcher, Research Institute of Physical and Organic Chemistry
Russian Federation, Rostov-on-DonReferences
- Зарубина И.В., Шабанов П.Д. Молекулярная фармакология антигипоксантов. – СПб.: Н-Л, 2004. – 368 с. [Zarubina IV, Shabanov PD. Molekulyarnaya farmakologiya antigipoksantov. Saint Petersburg: N-L; 2004. 368 p. (In Russ.)]
- Оковитый С.В., Шуленин С.Н., Смирнов А.В. Клиническая фармакология антигипоксантов и антиоксидантов. – СПб.: ФАРМиндекс, 2005. – 72 с. [Okovityy SV, Shulenin SN, Smirnov AV. Klinicheskaya farmakologiya antigipoksantov i antioksidantov. Saint Petersburg: FARMindeks; 2005. 72 p. (In Russ.)]
- Зайчик А.Ш., Гурилов Л.П. Патофизиология. Том 2. Основы патохимии. – СПб.: ЭЛБИ, 2000. – 687с. [Zaychik AS, Gurilov LP. Patofiziologiya. Tom 2. Osnovy patokhimii. Saint Petersburg: ELBI; 2000. 687 p. (In Russ.)]
- Чеснокова Н.П. Типовые патологические процессы: Учебное пособие. – Саратов: Издательство Саратовского государственного медицинского университета, 2004. [Chesnokova NP. Tipovye patologicheskie protsessy: Uchebnoe posobie. Saratov: Izdatel’stvo Saratovskogo gosudarstvennogo meditsinskogo universiteta; 2004. (In Russ.)]
- Radi R. Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci USA. 2018;115(23):5839-5848. https://doi.org/10.1073/pnas.1804932115.
- Биленко М.В. Ишемические и реперфузионные повреждения органов. – М.: Медицина, 1989. – 368 с. [Bilenko MV. Ishemicheskie i reperfuzionnye povrezhdeniya organov. Moscow: Meditsina; 1989. 368 p. (In Russ.)]
- Gorlach A, Dimova EY, Petry A, et al. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved? Redox Biol. 2015;6:372-385. https://doi.org/10.1016/j.redox.2015.08.016.
- Anisimova VA, Spasov AA, Kosolapov VA, et al. Synthesis and biological activity of 9-dialkylaminoethyl-2-oxy(dioxy)-phenylimidazo[1,2-a]benzimidazoles. Pharm Chem J. 2006;40(10):521-9. https://doi.org/10.1007/s11094-006-0185-5.
- Zhukovskaya ON, Anisimova VA, Spasov AA, et al. 1-Substituted 2-Benzylaminobenzimidazoles with Phenyl Methoxyls: Synthesis, Computer Prediction, and Pharmacological Activity. Pharm Chem J. 2016;49(11):735-742. https://doi.org/10.1007/s11094-016-1362-9.
- Косолапов В.А., Спасов А.А., Анисимова В.А. Изучение антирадикальной активности новых соединений методами хемилюминесценции // Биомедицинская химия. – 2005. – Т. 51. – № 3. – С. 287–294. [Kosolapov VA, Spasov AA, Anisimova VA. Study of antiradicalactivity of new compounds by chemiluminescence. Biomed Khim. 2005;51(3):287-294. (In Russ.)]
- Патент РФ № 2391979/ 12.05.2008. Бюл. № 17. Анисимова В.А., Косолапов В.А., Минкин В.И., и др. Дигидробромид 9-(3,4-дигидроксифенил)-9-диэтиламииноэтилимидазо[1,2-а]бензимидазола и фармацевтическая композиция на его основе. [Patent RUS No 2391979/ 12.05.2008. Byul. No 17. Anisimova VA, Kosolapov VA, Minkin VI, et al. Digidrobromid 9-(3,4-digidroksifenil)-9-dietilamiinoetilimidazo[1,2-a]benzimidazola i farmatsevticheskaya kompozitsiya na ego osnove. (In Russ.)]
- Лукьянова Л.Д. Методические рекомендации к экспериментальному изучению препаратов, предназначенных для клинического изучения в качестве антигипоксических средств. – М., 1990. – 18 с. [Luk’yanova LD. Metodicheskie rekomendatsii k eksperimental’nomu izucheniyu preparatov, prednaznachennykh dlya klinicheskogo izucheniya v kachestve antigipoksicheskikh sredstv. Moscow; 1990. 18 p. (In Russ.)]
- Кораблев М.В., Лукиенко П.И. Противогипоксические средства. – Минск: Беларусь, 1976. – 127 с. [Korablev MV, Lukienko PI. Protivogipoksicheskie sredstva. Minsk: Belarus’; 1976. 127 p. (In Russ.)]
- Рощина Л.Ф., Островская Р.У. Влияние пирацетама на устойчивость организма к гипоксии // Фармакология и токсикология. – 1981. – Т. 44. – № 2. – С. 210–212. [Roshchina LF, Ostrovskaya RU. Vliyanie piratsetama na ustoychivost’ organizma k gipoksii. Farmakol Toksikol.1981;44(2):210-212. (In Russ.)]
- Крапивин С.В., Шаповалов С.В., Романова В.Е., и др. Изучение влияния периодической адаптации к гипоксии на состояние ЦНС крыс с различной резистентностью к кислородной недостаточности // Журнал высшей нервной деятельности им. И.П. Павлова. – 1992. – Т. 42. – № 1. – С. 164–168. [Krapivin SV, Shapovalov SV, Romanova VE, et al. Izuchenie vliyaniya periodicheskoy adaptatsii k gipoksii na sostoyanie TsNS krys s razlichnoy rezistentnost’yu k kislorodnoy nedostatochnosti. Zh Vyssh Nerv Deiat im IP Pavlova. 1992;42(1):164-168. (In Russ.)]
