The experimental study of the antihypoxic and antioxidant activity of 5,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidine derivatives

Authors

  • V. A. Volkovoy National University of Pharmacy, Ukraine
  • O. V. Sevrukov National University of Pharmacy, Ukraine
  • S. V. Kolisnyk National University of Pharmacy, Ukraine
  • N. V. Derkach National University of Pharmacy, Ukraine
  • S. I. Kryzhna Kharkiv Medical Academy of Postgraduate Education, Ukraine
  • M. O. Ostapets National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/nphj.17.2173

Keywords:

derivatives of 5, 7-dihydro-1H-pyrrolo-[2, 3-d]pyrimidine, hypoxia, antihypoxic action, lipid peroxidation, hepatitis, antioxidant activity

Abstract

Aim. To study the antihypoxic and antioxidant activity of 5,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidine derivatives on the models of the experimental pathology.
Materials and methods. The study of the antihypoxic activity of 5,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidine derivatives was conducted on the model of acute hemic hypoxia, the antioxidant action was studied on the model of toxic tetrachlorometane hepatitis.
Results and discussion. It was found that the activity of compounds KMS-161, KMS-164, KMS-166, KMS-168, KMS-174, KMS-176, KMS-191 was lower compared to mexidol, and the antihypoxic activity of compounds KMS-162, KMS-163, KMS-172, KMS-178, KMS-179, KMS-211, KMS-214, KMS-217 was close and slightly higher than the activity of mexidol in its median effective dose of 100 mg/kg. The marked antihypoxic activity was found in all groups studied. In the “structure – activity” analysis it was found that the antihypoxic activity among derivatives of 5,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidine was caused by their nature, the structure of the radical and the position of the substituent. The presence of the pyrrole ring in the molecule of 5,7-dihydro-1Н-pyrrolo-[2,3-d]pyrimidine led to the increased antihypoxic activity. A comparative analysis of the effectiveness of the objects studied showed that substances with the code of KMS-162, KMS-176, KMS-191, KMS-211, KMS-214, KMS-217 affected most positively on the state of AOS and LPO in conditions of acute hepatitis.
Conclusions. In a series of 5,7-dihydro-1Н-pyrrolo-[2,3-d]pyrimidine derivatives the most active was compound KMS-211, which showed the high antihypoxic activity (131 %) in relation to the control group and exceeded the reference drug mexidol by 45 %. Synthetic derivatives of 5,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidine exhibited the antioxidant activity (compound KMS-211 was the most active). The compounds studied may be the basis for the purposeful synthesis of antihypoxants and antioxidants.

Author Biographies

V. A. Volkovoy, National University of Pharmacy

Doctor of Medicine (Dr. habil.), professor of the Department of Pathological Physiology

O. V. Sevrukov, National University of Pharmacy

postgraduate student of the Department of Pathological Physiology

S. V. Kolisnyk, National University of Pharmacy

Doctor of Pharmacy (Dr. habil.), professor of the Analytical Chemistry Department

N. V. Derkach, National University of Pharmacy

Candidate of Biology (PhD), associate professor of the Department of Human Physiology and Anatomy

S. I. Kryzhna, Kharkiv Medical Academy of Postgraduate Education

Doctor of Medicine (Dr. habil.), professor of the Department of Clinical Pathophysiology, Topographic Anatomy and Operative Surgery

M. O. Ostapets, National University of Pharmacy

Candidate of Medicine (PhD), teaching assistant of the Department of Pathological Physiology

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Published

2017-09-12

Issue

No. 3(91) (2017)

Section

Experimental and Clinical Pharmacology

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