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

Date

2018-09-01

Author

KÜÇÜKOĞLU, KAAN
GÜL, Mustafa
GÜL, Halise İnci
Atalay, Rengül
Geny, Bernard

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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 mu M, respectively, showed higher cytotoxic potency than the reference compound 5-FU with 7.0 mu M 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 mu M 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.

Subject Keywords

General Pharmacology, Toxicology and Pharmaceutics, Organic Chemistry

URI

https://hdl.handle.net/11511/62972

Journal

MEDICINAL CHEMISTRY RESEARCH

DOI

https://doi.org/10.1007/s00044-018-2220-y

Collections

Graduate School of Informatics, Article

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Citation Formats

K. KÜÇÜKOĞLU, M. GÜL, H. İ. GÜL, R. Atalay, and B. Geny, “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,” MEDICINAL CHEMISTRY RESEARCH, pp. 2116–2124, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/62972.