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Synthesis, and docking studies of arylhydrazone compounds and evaluation of their platelet aggregation inhibitory effect and cytotoxicity

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Abstract

In view of proven antiplatelet activity of hydrazone group containing compounds, two series of hydrazone derivatives were synthesized by coupling appropriate aldehydes with phenyl hydrazine and Isonicotinic acid in the presence of distilled water and a catalytic amount of glacial acetic acid. All synthesized compounds were screened for their antiplatelet activity against induced aggregation by adenosine diphosphate (ADP) and arachidonic acid (AA). The results indicate that compounds in arylhydrazone group had shown satisfactory activity. Among them, 1-(3-methoxybenzylidene)-2-phenylhydrazine (1c), 2-methoxy-4-(2-phenylhydrazono) methyl phenol (1g), and 2-((2-phenylhydrazono) methyl)-1H-pyrrole (1h) were found to be the most potent antiplatelet compounds with IC50 less than 39 μM. Furthermore, the cell toxicity assay, (MTT test) indicates 1h is noncytotoxic in various cell lines, and other two manifested marginal safety of 3 to 4 times of IC50. None of the synthesized N-isonicotinohydrazide derivatives in this study excreted sufficient antiplatelet activity.

Two groups of arylhydrazone compounds were synthesized and their activity against platelet aggregation were screened in addition to the cytotoxicity of best performing compounds. Three compounds in Phenylhydrazone compounds showed significant activities against Arachidonic induced platelet aggregation.

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Acknowledgements

The authors would like to thank Kimia Tabib for her kind assistance.

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Author notes

  1. Maryam H. Klidsar

    Present address: Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

Authors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Science, Vali Asr Avenue, Niayesh Junction, Tehran, Iran

    Maryam H. Klidsar, Marjan Esfahanizadeh, Pantea Haghverdi, Salimeh Amidi & Farzad Kobarfard

  2. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Vali Asr Ave. Niayesh Junction, Tehran, Iran

    Marjan Esfahanizadeh & Farzad Kobarfard

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  1. Maryam H. Klidsar
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Correspondence to Farzad Kobarfard.

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Klidsar, M.H., Esfahanizadeh, M., Haghverdi, P. et al. Synthesis, and docking studies of arylhydrazone compounds and evaluation of their platelet aggregation inhibitory effect and cytotoxicity. Med Chem Res 31, 1611–1620 (2022). https://doi.org/10.1007/s00044-022-02931-w

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