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Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones

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Abstract

N,N’-Bis[1-aryl-3-pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides (R1–R7) were synthesized by the reaction of 2 mols of 1-aryl-3-(pyrrolidine-1-yl)-1-propanone hydrochlorides with 1 mol of hydrazine hydrate and reported for the first time with their detailed spectral analysis and cytotoxicities towards human hepatoma (Huh7) and breast cancer (T47D) cell lines. Compounds R2, R6, and R7 with the IC50 values of 5.16, 6.96, and 5.96 μM, respectively, showed higher cytotoxic potency than the reference compound 5-FU with 7.0 μM against Huh7 cell line. However, all compounds did not show better cytotoxic activities than 5-FU against T47D cell line at the conditions studied. The representative compound of series, R2, inhibited the mitochondrial respiration at 90, 165, and 265 µM concentrations in a dose dependent manner in liver homogenates, suggesting that mitochondrial respiration may be one of the contributing factor to the cytotoxicity of the compounds synthesized. The compounds R2, R6, and R7 can be chosen as the leader compounds of this study for further studies.

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Acknowledgements

This study was supported by the Research Foundation of Atatürk University and the KANILTEK anticancer biomolecule screening facility, Bilkent University.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bülent Ecevit University, Zonguldak, Turkey

    Kaan Kucukoglu

  2. Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey

    Mustafa Gul

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey

    Halise Inci Gul

  4. Cancer Systems Biology Lab. Graduate School of Informatics, METU, TR-06800, Ankara, Turkey

    Rengul Cetin-Atalay

  5. Fédération de Médecine Translationnelle, Faculté de Médecine-EA 3072, Université de Strasbourg, Strasbourg, France

    Bernard Geny

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  1. Kaan Kucukoglu
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  2. Mustafa Gul
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Correspondence to Kaan Kucukoglu.

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Kucukoglu, K., Gul, M., Gul, H.I. et al. Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones. Med Chem Res 27, 2116–2124 (2018). https://doi.org/10.1007/s00044-018-2220-y

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