ANALGESIC AND ANTIDEPRESSANT ACTIVITY OF 8-SUBSTITUTED HARMINE DERIVATIVES

Authors

  • Roza B. Seidakhmetova JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan
  • Asel Amanzhan JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan
  • Elvira E. Schults N.N.Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., Novosibirsk 630090, Russia
  • Kristina V. Goldaeva JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan
  • Sergazy M. Adekenov JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan
  • Dmitriy Berillo Department of Pharmaceutical and Toxicological Chemistry, Pharmacognosy, and Botany, School of Pharmacy, Asfendiyarov Kazakh National Medical University, 94 Tole Bi St., Almaty, Kazakhstan

DOI:

https://doi.org/10.1007/6580

Keywords:

alkaloids, harmine, analgesic activity, antidepressant effect, molecular docking.

Abstract

The present study describes the synthesis of a novel type of harmine derivatives, containing substituent at the C-8 position and their physicochemical characterization by FTIR, NMR, and elemental analysis. Computer simulation of the interaction of harmine and its derivatives (Z)-8-(1-hydrazonoethyl)-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole and 8-{(Z)-1-[(Z)-1-(2-fluorophenyl)hydrazono]ethyl}-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole with biological targets dopamine D2 receptor and enzymes monoamine oxidase A and B is discussed. Harmine alkaloid derivatives were studied for antidepressant and analgesic activity. It was found that 8-{(Z)-1-[(Z)-(2-fluorophenyl)hydrazono]ethyl}-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole at a dose of 10 mg/kg exhibited antidepressant effect in the Porsolt behavioral despair test. (Z)-8-(1-Hydrazonoethyl)-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole has a pronounced analgesic activity. Modeling of biological activity using PASS software predicted HIV attachment inhibiting, antimycobacterial, antituberculosic, histamine release inhibiting, cytochrome P450 stimulating, and various antineoplastic activities for synthesized harmine derivatives with high probability.

Author Biographies

Roza B. Seidakhmetova, JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan

MD , department of pharmacology

Asel Amanzhan, JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan

PhD student, department of organic chemistry

Elvira E. Schults, N.N.Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., Novosibirsk 630090, Russia

Prof., oranic chemistry department

Kristina V. Goldaeva, JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan

MD, department pharmacology

Sergazy M. Adekenov, JSC International Scientific and Production Holding ''Phytochemistry'', 4 Gazalieva St., Karaganda 100009, Kazakhstan

Prof., head of the JSC "International Scientific and Production Holding" Phytochemistry "

Dmitriy Berillo, Department of Pharmaceutical and Toxicological Chemistry, Pharmacognosy, and Botany, School of Pharmacy, Asfendiyarov Kazakh National Medical University, 94 Tole Bi St., Almaty, Kazakhstan

PhD in chemistry, docent Department of Pharmaceutical and Toxicological chemistry, Pharmacognosy and botany School of Pharmacy

Deputy Head of the Research Institute of Fundamental and Applied Medicine after B.A. Atchabarova Address: office 404, Tole bi street, 94, Almaty KZ

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Published

2022-07-21

Issue

Vol. 58 No. 6/7 (2022)

Section

Original Papers