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Analgesic and Antidepressant Activity of 8-Substituted Harmine Derivatives

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Chemistry of Heterocyclic Compounds Aims and scope

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.

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Authors and Affiliations

  1. JSC International Scientific and Production Holding “Phytochemistry”, 4 Gazalieva St., Karaganda, Kazakhstan, 100009

    Roza B. Seidakhmetova, Asel Amanzhan, Kristina V. Goldaeva & Sergazy M. Adekenov

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

    Elvira E. Shults

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

    Dmitriy Berillo

Authors
  1. Roza B. Seidakhmetova
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  2. Asel Amanzhan
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  3. Elvira E. Shults
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  4. Kristina V. Goldaeva
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  5. Sergazy M. Adekenov
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  6. Dmitriy Berillo
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Correspondence to Sergazy M. Adekenov or Dmitriy Berillo.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2022, 58(6/7), 324–332

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Seidakhmetova, R.B., Amanzhan, A., Shults, E.E. et al. Analgesic and Antidepressant Activity of 8-Substituted Harmine Derivatives. Chem Heterocycl Comp 58, 324–332 (2022). https://doi.org/10.1007/s10593-022-03092-9

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