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Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-\(c\)][1,2,4]triazin-6-amines

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Abstract

A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-\(c\)][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure–activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (\(\hbox {IC}_{50}\hbox {s} = 9.8-20.4\;\upmu \)M). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (\(\hbox {IC}_{50}\) values 12.1 and 13.0 \(\upmu \)M, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.

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Acknowledgments

This research was supported by grants from the Research Council of Tehran University of Medical Sciences and Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Tahmineh Akbarzadeh, Saeedeh Noushini, Somayeh Taban, Mohammad Mahdavi, Abbas Shafiee & Alireza Foroumadi

  2. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Tahmineh Akbarzadeh, Mina Saeedi & Reyhaneh Sabourian

  3. Medicinal & Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mahsima Khoshneviszadeh, Mehdi Khoshneviszadeh, Najmeh Edraki, Omidreza Firouzi & Ramin Miri

  4. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Saeed Emami

  5. Faculty of Chemistry, Mazandaran University, Babolsar, Iran

    Mohammad Eghtedari & Yaghoub Sarrafi

  6. Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran

    Maliheh Safavi

  7. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Kouros Divsalar, Mohammad Hassan Moshafi, Ali Asadipour & Alireza Foroumadi

Authors
  1. Tahmineh Akbarzadeh
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  2. Saeedeh Noushini
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Corresponding author

Correspondence to Alireza Foroumadi.

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Akbarzadeh, T., Noushini, S., Taban, S. et al. Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-\(c\)][1,2,4]triazin-6-amines. Mol Divers 19, 273–281 (2015). https://doi.org/10.1007/s11030-015-9566-6

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