Cardioprotective activity and screening of N-substituted of quinazolin-4(3Н)-ones


  • O. V. Dzhyhaliuk National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • H. I. Stepaniuk National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • K. P. Schabelnyk Zaporizhzhia State Medical University, Ukraine,
  • S. І. Kоvalenko Zaporizhzhia State Medical University, Ukraine,
  • O. S. Pashynska National Pirogov Memorial Medical University, Vinnytsia, Ukraine,



myocardial infarction, amiodarone, mexidol, thiotriazolin


Cardioprotection is a promising direction of therapy for myocardial infarction and the search for new substances with cardioprotective properties remains an urgent task in pharmacology. N-substituted quinazolin-4(3H)-ones, which are characterized by antihypoxic, antioxidant, angioprotective, anti-inflammatory, and others properties may have the cardioprotective activity.

The purpose of the study is to detect the presence and the degree of cardioprotective effect in a number of N-substituted quinazolin-4(3H)-ones in the model of acute experimental myocardial infarction in different modes of administration, to determine a “structure – action” dependence, to identify a leader compound promising for in-depth study of its pharmacological properties.

Materials and methods. 300 non-linear rats of both sexes, weighing 180–220 g, were used in this study. Myocardial infarction was modeled by diathermocoagulation of the coronary artery. In the 1st series of experiments, the studied substances and reference drugs amiodarone, mexidol and thiotriazoline were administered in the prophylactic, and in the 2nd series – in the therapeutic regimen. The cardioprotective effect size was estimated on the basis of the mortality rate of animals.

Results. The cardioprotective activity of both the test compounds and reference drugs was evidenced by a decrease in the mortality rate of animals with a heart attack in the critical periods of the experiment relative to the control. The PC-66 has been found to be the most effective: the mortality rate was 20 % versus 54 % of the control in the critical period of the experiment, that is, it was 2.7 times less than in the control. The test substances by the degree of cardioprotective effect in the course of therapeutic introduction into the body can be arranged in the following order: PC-66 = amiodarone ≥ mexidol ≥ thiotriazoline> PC-32 = PC-51. Cardioprotection, the signs of which were found in the PC-66 compound, are well combined with the presence of central analgesic and cerebroprotective effects, which suggests the multifactorial effects of this substance. We can state the originality of the resulting substance and its potential properties.

Conclusions. N-substituted quinazolin-4(3H)-ones exhibit cardioprotective activity. 4-(4-oxo-4H-quinazolin-3-yl) benzoic acid (compound PC-66) displays cardioprotective properties the most. The obtained data testify to the prospects of the pharmacological properties and safety of the PC-66 compound in-depth study.


Bavry, A. A., Park, K. E., Choi, C. Y., Mahmoud, A. N., Wen, X., & Elgendy, I. Y. (2017). Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study). Cardiology and Therapy, 6(1), 81–88. doi:

Elgendy, I. Y., Winchester, D. E., & Pepine, C. J. (2016). Experimental and early investigational drugs for angina pectoris. Expert Opinion on Investigational Drugs, 25(12), 1413–1421. doi: 10.1080/13543784.2016.1254617.

Feng, Y., LoGrasso, P. V., Defert, O., & Li, R. (2016) Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential. J Med Chem., 59(6), 2269–300. doi: 10.1021/acs.jmedchem.5b00683.

Fukushima, A., Milner, K., Gupta, A., & Lopaschuk, G. D. (2015) Myocardial Energy Substrate Metabolism in Heart Failure: from Pathways to Therapeutic Targets. Curr Pharm Des, 21(25), 3654–64. doi: 10.2174/1381612821666150710150445.

Gupta, A. K., Winchester, D., & Pepine, C. J. (2013). Antagonist molecules in the treatment of angina. Expert Opinion on Pharmacotherapy, 14(17), 2323–2342. doi: 10.1517/14656566.2013.834329.

Hausenloy, D. J., Garcia-Dorado, D., Bøtker, H. E., Davidson, S. M., Downey, J., Engel, F. B., et al. (2017). Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart. Cardiovascular research, 113(6), 564–585. doi: 10.1093/cvr/cvx049.

Houser, S. R., Margulies, K. B., Murphy, A. M., Spinale, F. G., Francis, G. S., Prabhu, S. D., et al. (2012). Animal models of heart failure: a scientific statement from the American Heart Association. Circulation Research, 111(1), 131–150. doi: 10.1161/RES.0b013e3182582523.

Moyé, L. (2016). Statistical Methods for Cardiovascular Researchers Circulation Research, 118(3), 439–453. doi: 10.1161/CIRCRESAHA.115.306305.

Toziuk, O., Kryvoviaz, O., Kryvoviaz, S., Ivko, T., & Balicka O. (2017). Effect of 5-R-Thio-Tetrazolo (1, 5-C)Quinazoline Derivatives on the Physical Performance in Different Types of Physical Exercise. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm, 11(3). S532–S535. doi:

O’Gara, P. T., Kushner, F. G., Ascheim, D. D., Casey, D. E. Jr., Chung, M. K., de Lemos, J. A., et al. (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulatio, 2013, 127(4), e362–e425. doi: 10.1161/CIR.0b013e3182742cf6.

Neri, M., Riezzo, I., Pascale, N., Pomara, C., & Turillazzi, E. (2017). Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists. Mediators of Inflammation, 2017, 7018393. doi: 10.1155/2017/7018393.

Oh, K. S., Oh, B. K., Park, C. H., Seo, H. W., Kang, N. S., Lee, J. H., et al. (2013) Cardiovascular effects of a novel selective Rho kinase inhibitor, 2-(1H-indazole-5-yl)amino-4-methoxy-6-piperazino triazine (DW1865). Eur J Pharmacol., 702(1–3), 218–26. doi: 10.1016/j.ejphar.2013.01.027.

Polegato, B. F., Minicucci, M. F., Azevedo, P. S., Gonçalves, A. F., Lima, A. F., Martinez, P. & F., Zornoff, L. A. M. (2016). Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats. Arquivos Brasileiros de Cardiologia, 106(2), 105–112. doi: 10.5935/abc.20160015.

Qintar, M., Spertus, J. A., Gosch, K. L., Beltrame, J., Kureshi, F., Shafiq, A., & Arnold, S. V. (2016). Effect of angina under-recognition on treatment in outpatients with stable ischaemic heart disease. European Heart Journal. Quality of Care & Clinical Outcomes, 2(3), 208–214. doi: 10.1093/ehjqcco/qcw016.

Shahin, R., Shaheen, O., El-Dahiyat, F., Habash, M., & Saffour, S. (2017). Research advances in kinase enzymes and inhibitors for cardiovascular disease treatment. Future Science OA, 3(4), FSO204. doi: 10.4155/fsoa-2017-0010.

Shamsuzzaman, M. A., Ali, A., Mashrai, A., Khanam, H., Sherwani, M., & Owais, M. (2014) Design, synthesis and biological evaluation of steroidal tetrazoles as antiproliferative and antioxidant agents. Eur. Chem. Bull., 3(11), 1075–1080.

Shugalei, I., Ilyushin, M., Sokolova, V., Dubjago, N., Bachurina, I., & Garabadzhiu, A. (2013) Complex copper compounds with pentaaminotetrazole are the new challenge in treatment and prevention of free-radical conditions. Chem. J. Moldovа, 8(1), 6–13.

Stepanyuk, G. I., Tozyuk, О. Y., Chornoivan, N. G., Kovalenko, S. I., & Voskoboynik, O. Y. (2012) Vplyv pokhidnykh tetrazolo(1,5-s)khinazolinu na fizychnu vytryvalist shchuriv pry riznykh temperaturnykh rezhymakh [Effect of tetrazol[1,5-c]quinasoline derivatives on the rats physical endurance at different temperatures]. Ukrainskyi zhurnal klinichnoi ta laboratornoi medytsyny, 7(4), 81–85. [in Ukrainian].

Stirrup, J., Velasco, A., Hage, F. G., & Reyes, E. (2017). Comparison of ESC and ACC/AHA guidelines for myocardial revascularization. Journal of Nuclear Cardiology, 24(3), 1046–1053. doi: 10.1007/s12350-017-0811-5.

How to Cite

Dzhyhaliuk OV, Stepaniuk HI, Schabelnyk KP, Kоvalenko SІ, Pashynska OS. Cardioprotective activity and screening of N-substituted of quinazolin-4(3Н)-ones. Zaporozhye Medical Journal [Internet]. 2019Feb.8 [cited 2024Jul.20];(1). Available from:



Original research