DOI: https://doi.org/10.24959/ophcj.19.960

The search for substances with the antimicrobial activity among morpholine-containing 2-R-phenyliminothiazole derivatives

H. O. Yeromina, T. V. Upyr, T. P. Osolodchenko, Z. G. Ieromina, N. R. Demchenko, L. O. Perekhoda

Abstract


The treatment of infectious diseases is one of the global problems of modern medicine. Despite the large amount of medications the problem of creation of new highly effective antimicrobials is a relevant task. This is, mainly, due to the increase of microbial resistance to the widely used antimicrobials. One of the promising ways to solve this task is the search and creation of new antimicrobial substances.

Aim. To search for the substances with the antimicrobial activity among derivatives of morpholine-containing 2-R-phenyliminothiazole, namely N-[4-methyl-2-(R-phenylimino)thiazol-3-yl]-morpholine derivatives.

Results and discussion. The results of the biological screening demonstrated that all compounds studied in the concentration of 1 % revealed the antibacterial and antifungal effect. It was determined that the compounds had the most pronounced antibacterial effect on gram-positive strains of microorganisms (with the average diameter of the inhibition zones of 23-27 mm) and a little less effect on gram-negative strains of microorganisms (with the average diameter of the inhibition zones of 15-25 mm). Compound 3c – N-[4-methyl-2-(2’,5’-dimethylphenylimino)thiazol-3-yl]morpholine hydrochloride showed the highest activity against all strains of microorganisms tested.

Experimental part. The biological screening for the antimicrobial activity was carried out in vitro by the agar diffusion method (“wells” method).

Conclusions. It has been found that N-[4-methyl-2-(R-phenylimino)thiazol-3-yl]-morpholine derivatives can be promising objects for further in-depth studies of the antimicrobial activity and for creating new effective antimicrobial drugs.


Keywords


derivatives of 2-R-phenyliminothiazole; synthesis; Hantzsch reaction; antimicrobial properties; agar diffusion method

References


Vorotey, E. S., Voronkova, L. S., Vinnikov, A. I. (2015). Chutlivist plivkoutvoryuyuchih ta neplivkoutvoryuyuchih shtamiv St. aureus do antibiotikiv ta likuvalnih preparativ. Visnik problem biologiyi ta meditsini, 2 (4), 227–282.

Tulasidas, S., Rao, P., Bhat, S., & Manipura, R. (2018). A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections. Infection and Drug Resistance, Volume 11, 2443–2448. https://doi.org/10.2147/idr.s179462

3. Ustoichivost k antibiotikam: Informatcionnyi biulleten. (2016). Vsemirnaia organizatciia zdorovia. Tcentr SMI. Zheneva. Available at: https://www.who.int/ru/news-room/fact-sheets/detail/antibiotic-resistance

Koftyreva, L. A., Egorova, S. A., Kozhukhova, E. A., Makarova, M. A., Kozlova, N. S., Matveeva, Z. N., Shestakova, T. I., Petrova, L. Iu., & Kicha, E. V. (2009). Kazanskii meditcinskii zhurnal, 90 (5), 699–704.

Foster, T. J. (2017). Antibiotic resistance in Staphylococcus aureus. Current status and future prospects. FEMS Microbiology Reviews, 41 (3), 430–449. https://doi.org/10.1093/femsre/fux007

Boichuk, T. N., Burdeynyuk, I.P., Myslytsky, V. F., Khodorowskiy, V. M., & Chornous, V. A. (2016). Bactericidal and antifungal activity of quaternary ammonium salts – a derivative of diphenhydramine. Clinical & Experimental Pathology, 15 (2). https://doi.org/10.24061/1727-4338.XV.2.56.2016.8

Gotsulya, A. S., Kamyshnyi, O. M., Polishchuk, N. M., Panasenko, O. I., & Knysh, Y. G. (2015). Research of the antimicrobial and antifungal activity of 7–((3–thio–4–R–4H–1,2,4–triazoles–3–yl)methyl)theophylline S-derivatives. Zaporozhye Medical Journal, 4 (91), 95–99. http://dx.doi.org/10.14739/2310-1210.2015.4.50302

Terenteva, E., Sasmakov, S., Azimov, Sh., Vinogradova, V., Abdurakhmanov, D., Khashimova, Z., & Saidov, A. (2017). Visnyk Kyivskoho natsionalnoho universytetu imeni Tarasa Shevchenka. Biolohiia, (2), 51–55.

Anusionwu, C. G., Aderibigbe, B. A., & Mbianda, X. Y. (2018). Hybrid molecules development : A versatile landscape for the control of antifungal drug resistance-A Review. Mini-Reviews in Medicinal Chemistry, 19. https://doi.org/10.2174/1389557519666181210162003

Kulakov, I. V., Nurkenov, O. A., Ahmetova, S. B., Seydahmetova, R. B., Zhambekov, Z. M. (2011). KhimikoFarmatsevticheskii Zhurnal, 45 (1), 17–20.

Sarymzakova, R. K., Dzhamanbaev, Zh. A., Abdurashitova, Iu. A., Suleimanova, Sh. S., Sarymzakova, B. K. (2016). Uspekhi sovremennogo estestvoznaniia, 2, 65–69

Vartanyan, S. O., Sargsyan, A. B., Avakyan, A. S., Agekyan, A. A., Stepanyan, G. M., Paronikyan, R. V. (2015). Him. zhurn. Armenii, 68 (2), 251–258.

Semwal, A., Nigam, A., Singh, D. C. P. (2011). Synthesis, Characterization and Biological Activity of Novel N–p–methylbenzoyl-N-substituted thiourea. IJDDD, 2 (4), 654–658.

Ivanov, D.D., Dombrovskii, Ia.A. (2015). Pochki, 4 (14), 50–54.

Perekhoda, L. O., Yeromina, H. O., Drapak, I. V., Sych, I. A., Demchenko, A. M., & Komykhov, S. O. (2016). The synthesis of N–[4–methyl(41–chlorophenyl) –2–R–phenylіmіnothіazol–3–yl]-morpholine derivatives by Hantzsch reaction. Žurnal Organìčnoï Ta Farmacevtičnoï Hìmìï, 14 (3 (55)), 52–57. https://doi.org/10.24959/ophcj.16.890

Coyle, M. B. (2005). Manual of Antimicrobial Susceptibility Testing. American Society for Microbiology. American Society for Microbiology, 236.


GOST Style Citations


1.         Воротей, Є. С. Чутливість плівкоутворюючих та неплівкоутворюючих штамів St. aureus до антибіотиків та лікувальних препаратів –бактеріофагів / Є. С. Воротей, Л. С. Воронкова, А. І. Вінніков // Вісник проблем біол. та медицини. – 2015. – Вип. 2 (4). – С. 227–282.

2.         A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections / S. Tulasidas, P. Rao, Bhat, R. Manipura // Infect. Drug Resist. – 2018. – Vol. 11. – P. 2443–2448. https://doi.org/10.2147/idr.s179462 

3.         Устойчивость к антибиотикам: Информационный бюллетень. Всемирная организация здоровья. Центр СМИ. Женева. – 2016. – Available at : https://www.who.int/ru/news-room/fact-sheets/detail/antibiotic-resistance

4.         Резистентность энтеробактерий к антимикробным препаратам выбора при лечении острых кишечных инфекций / Л. А. Кафтырева, С. А. Егорова, Е. А. Кожухова и др. // Казанский мед. журн. – 2009. – № 90 (5). – С. 699–704.

5.         Foster, T. J. Antibiotic resistance in Staphylococcus aureus. Current status and future prospects / T. J. Foster // FEMS Microbiol Rev. – 2017. – Vol. 1, Iss. 41 (3). – P. 430–449. https://doi.org/10.1093/femsre/fux007 

6.         Бактерицидна та протигрибкова активність біс–четвертинних амонійних солей, що містять фрагмент димедролу / Т. М. Бойчук, І. П. Бурденюк, В. Ф. Мислицький та ін. // Clin. and Experim. Pathol. – 2016. – Vol. 15, № 2 (56). – P. 39–41. https://doi.org/10.24061/1727-4338.XV.2.56.2016.8  

7.         Research of the antimicrobial and antifungal activity of 7–((3–thio–4–R–4H–1,2,4–triazoles–3–yl)methyl)theophylline S–derivatives. / A. S. Gotsulya, O. M. Kamyshnyi, N. M. Polishchuk et al. // Запорожский мед. журн. – 2015. – №4 (91). – С. 95–99. http://dx.doi.org/10.14739/2310-1210.2015.4.50302

8.         Противомикробная активность и токсичность алкилтетрагидроизохинолинов / Е. Терентьева, С. Сасмаков, Ш. Азимов и др. // Вісник Київського нац. ун-ту імені Тараса Шевченка. Біологія. – 2017. – Вип. 2. – С. 51–55.

9.         Anusionwu, C. G. Hybrid molecules development : A versatile landscape for the control of antifungal drug resistance–A Review / C. G. Anusionwu, B. A. Aderibigbe, X. Y. Mbianda // Mini Rev. Med. Chem. – 2018. – Vol. 19. https://doi.org/10.2174/1389557519666181210162003 

10.       Синтез, антибактериальная и противогрибковая активность тиомочевинных производных алкалоида анабазина / И. В. Кулаков, О. А. Нуркенов, С. Б. Ахметова и др. // Хим.–фарм. журн. – 2011. – Т. 45, № 1. – С. 17–20.

11.       Синтез и свойства углеводных производных гетероциклических соединений / Р. К. Сарымзакова, Ж. А. Джаманбаев, Ю. А. Абдурашитова и др. // Успехи совр. естествознания. – 2016. – № 2. – С. 65–69.

12.       Синтез и изучение антибактериальных свойств новых дизамещенных производных тиомочевин / С. О. Вартанян, А. Б. Саргсян, А. С. Авакян и др. // Хим. журн. Армении. – 2015. – Т. 68, № 2. – С. 251–258.

13.       Semwal, A. Synthesis, Characterization and Biological Activity of Novel N–p–methylbenzoyl–N–substituted thiourea / A. Semwal, A. Nigam, D. C. P. Singh // Intern. J. of Drug Design and Discovery. – 2011. – Vol. 2, № 4. – P. 654–658.

14.       Иванов, Д. Д. Применение препаратов группы оксазолидинонов в терапии инфекции мочевыводящих путей / Д. Д. Иванов, Я. А. Домбровский // Почки. – 2015. – № 4 (14). – С. 50–54.

15.       Синтез похідних N–[4–метил(41–хлорофеніл)–2–R–фенілімінотіазол–3–іл]–морфоліну за реакцією Ганча / Л. О. Перехода, Г. О. Єрьоміна, І. В. Драпак та ін. // Журн. орг. та фарм. хімії. – 2016. – Т. 14, № 3 (55). – С. 52–57.  https://doi.org/10.24959/ophcj.16.890 

16.       Coyle, M. B. Manual of Antimicrobial Susceptibility Testing. American Society for Microbiology / M. B. Coyle. –Washington: American Society for Microbiology, 2005. – 236 p.





Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)