Effects of Ferrocenyl 4-(Imino)-1,4-Dihydro-quinolines on Xenopus laevis Prophase I - Arrested Oocytes: Survival and Hormonal-Induced M-Phase Entry

• DOI: 10.3390/ijms21093049
• Publication Date: 2020-04-28T09:05:32Z
• Authors: Guillaume Marchand; Nathalie Wambang; Sylvain Pellegrini; Caroline Molinaro; Alain Martoriati; Till Bousquet; Angel Markey; Arlette Lescuyer-...; Jean-François Bodart; Katia Cailliau; Lydie Pelinski; Matthieu Marin
• Keywords: ferrocenyldihydroquinoline; Cyclin B; Xenopus Proteins; Article; Histones; Xenopus laevis; 03 medical and health sciences; Cell Line, Tumor; CDC2 Protein Kinase; Animals; Humans; Ferrous Compounds; Meiotic Prophase I; Phosphorylation; oocyte; Progesterone; Cell Proliferation; 0303 health sciences; Molecular Structure; 3. Good health; cell death; Gene Expression Regulation; metaphase II spindle; Oocytes; Quinolines; Female; HeLa Cells

Xenopus oocytes were used as cellular and molecular sentinels to assess the effects of a new class of organometallic compounds called ferrocenyl dihydroquinolines that have been developed as potential anti-cancer agents. One ferrocenyl dihydroquinoline compound exerted deleterious effects on oocyte survival after 48 h of incubation at 100 μM. Two ferrocenyl dihydroquinoline compounds had an inhibitory effect on the resumption of progesterone induced oocyte meiosis, compared to controls without ferrocenyl groups. In these inhibited oocytes, no MPF (Cdk1/cyclin B) activity was detected by western blot analysis as shown by the lack of phosphorylation of histone H3. The dephosphorylation of the inhibitory Y15 residue of Cdk1 occurred but cyclin B was degraded. Moreover, two apoptotic death markers, the active caspase 3 and the phosphorylated histone H2, were detected. Only 7-chloro-1-ferrocenylmethyl-4-(phenylylimino)-1,4-dihydroquinoline (8) did not show any toxicity and allowed the assembly of a histologically normal metaphase II meiotic spindle while inhibiting the proliferation of cancer cell lines with a low IC50, suggesting that this compound appears suitable as an antimitotic agent.