Study of wound-healing activity of sodium 2-(adamantane-1-yl)-2-hydrazino-5-phenyl-4-oxobutanoate

Abstract

Objective. To study a wound-healing activity of the earlier synthesized ‘compound-leader” sodium 2- (adamantan-1-yl)-2-hydrazino-5-phenyl-4-oxobutenoate (1), as well as to establish the possibility of its practical application in the ointment dosage form.

Materials and methods. The “substance-leader” 1 was synthesized by the chemical methods described earlier. The experimental 5 % ointment composition based on an aqueous solution of sodium alginate was developed in compliance with the rules for preparing homogeneous ointments. Its effect on the healing of linear aseptic skin wounds in white rats was studied by the method of wound-tensiometry.

Results. The experimental 5 % ointment composition with compound 1 was found to significantly increase the scar tensile strength compared to control without treatment. The developed model ointment showed wound-healing activity comparable to that of the reference drug (Levomekol ointment).

Conclusions. The selected “substance-leader” 1 in the composition of a model 5 % hydrophilic ointment based on sodium alginate exhibits pronounced biological activity and is a candidate for further research as a potential pharmaceutical substance with complex wound-healing and anti-inflammatory property.

Keywords

Hydrazine derivatives of 2,4-dioxobutanoic acids / ointment / wound-healing activity

References

[1] Kozhukhar V.Yu., Kuznetsov A.S., Pulina N.A., Makhmudov R.R., Rubtsov A.E. Study of the analgesic activity of new compounds containing fragments of morpholine, piperazine and adamantane. Sovremennye problemy nauki i obrazovaniya 2015; 3, available at: http://www.science-education.ru/ru/article/view?id = 17523 (in Russian).

[2] Кожухарь В.Ю., Кузнецов А.С., Пулина Н.А., Махмудов Р.Р., Рубцов А.Е. Исследование анальгетической активности новых соединений, содержащих фрагменты морфолина, пиперазина и адамантана. Современные проблемы науки и образования 2015; 3, available at: http://www.science-education.ru/ru/article/view?id = 17523.

[3] Kuznetsov A.S., Dubrovina S.S., Pulina N.A. Antimicrobial activity of new 4-(het)aryl-4-oxobut-2-enoic acids derivatives. Pharmacy 2018; 4: 40–43 (in Russian).

[4] Кузнецов А.С., Дубровина С.С., Пулина Н.А. Противомикробная активность новых производных 4-(гет)арил-4-оксобут-2-еновых кислот. Фармация 2018; 4: 40–43.

[5] Pulina N.A., Kuznetsov A.S., Krasnova A.I., Novikova V.V. Synthesis, antimicrobial activity, and behavioral response effects of n-substituted 4-aryl-2-hydroxy-4-oxobut-2-enoic acid hydrazides and their metal complexes. Pharmaceutical chemistry journal 2019; 53 (3): 220–224 (in Russian).

[6] Пулина Н.А., Кузнецов А.С., Краснова А.И., Новикова В.В. Синтез, антимикробная активность и влияние на поведенческие реакции N-замещенных гидразидов 4-арил-2-гидрокси-4-оксобут-2-еновых кислот и их комплексных производных. Химико-фармацевтический журнал 2019; 53 (3): 30–34.

[7] Pulina N.A., Kozhukhar V.Yu., Kuznetsov A.S., Starkova A.V., Rubtsov A.E. Synthesis and search for compounds with hemostatic activity in the series of 4-(het)aryl-4-oxobut-2-enoic acid derivatives. Russian Chemical Bulletin 2017; 8: 1497–1502 (in Russian).

[8] Пулина Н. А., Кожухарь В.Ю., Кузнецов А.С. Рубцов А.Е., Старкова А.В. Синтез и поиск соединений с гемостатической активностью в ряду производных 4-(гет)арил-4-оксобут-2-еновых кислот. Известия Академии наук. Серия химическая 2017; 8: 1497–502.

[9] Pulina N.A., Kuznetsov A.S., Chaschi- na S.V. Studying of analgesic and anti-inflammatory activity of 2,4-dioxobutanoic acid. Permskiy meditsinskiy zhurnal 2020; 37 (4): 115–119 (in Russian).

[10] Пулина Н.А., Кузнецов А.С., Чащина С.В. Изучение анальгетической и противовоспалительной активности гидразинопроизводных 2,4-диоксобутановых кислот. Пермский медицинский журнал 2020; 37(4); 115–119.

[11] State Pharmacopoeia of the Russian Federation of the Ministry of Health of the Russian Federation. 14th ed. Moscow 2018; 1: 1814 (in Russian).

[12] Государственная фармакопея Российской Федерации Министерства здравоохранения Российской Федерации. XIV изд. М. 2018; 1: 1814.

[13] Guidelines for conducting preclinical studies of drugs. Part One. Pod red. A.N. Mironova. Moscow: Grif i K 2013: 944 (in Russian).

[14] Руководство по проведению доклинических исследований лекарственных средств. Часть первая. Под ред. А.Н. Миронова. М.: Гриф и К 2013; 944.

[15] Gorbunov S.M., Zakonnikova I.V., Abdrakhmanova N.G. Device for determining the tensile strength of healing wounds. Farmakologicheskaja reguljacija regeneratornyh processov v jeksperimente i klinike. Joshkar-Ola 1979; 100–104 (in Russian).

[16] Горбунов С.М., Заиконникова И.В., Абдрахманова Н.Г. Устройство для определения прочности на разрыв заживающих ран. Фармакологическая регуляция регенераторных процессов в эксперименте и клинике. Йошкар-Ола 1979; 100–104.

RIGHTS & PERMISSIONS

Kuznetsov A.S., Pulina N.A., Chashchina S.V.