The length of the bridging chain in ansa-metallocenes influences their antiproliferative activity against triple negative breast cancer cells (TNBC).
In order to examine whether the length of the bridging chain in ansa-ferrocenes affects their antiproliferative activity against MDA-MB-231 triple negative breast cancer cell lines (TNBC), we synthesized derivatives of the type 1-[bis-(4-hydroxyphenyl)]methylidene-[n]ferrocenophane and 1-[(4-hydroxyphenyl)-phenyl]methylidene-[n]ferrocenophane with n = 3, 4, 5. We found that the derivatives of [3]ferrocenophane, the compounds with the shortest bridging chains, are the most active. IC50 values were 0.09 ± 0.01, 2.41 ± 0.10, and 1.85 ± 0.25 μM for the dihydroxyphenyl derivatives, with n = 3, 4, 5, respectively. These differences can be explained in terms of modification of the key metabolites (radical versus quinone methides) within the ansa series depending on the length of the bridging chain. The derivative of [5]ferrocenophane, possessing two -[bis-(4-hydroxyphenyl)]methylidene groups, was also prepared. Surprisingly, this relatively large molecule is also active (IC50 = 2.7 ± 0.3 μM). Two ruthenocenophane analogs were also synthesized. These ruthenium compounds are practically inactive against MDA-MB-231 cells. The unusual chemistry of these different compounds is discussed in terms of elucidating the mechanism underlying their diverse antiproliferative activity, and their specific advantages are evaluated.
Sorbonne Universités, UPMC Univ Paris 6, UMR 8232, IPCM, F-75005 Paris, France and CNRS, UMR 8232, IPCM, F-75005 Paris, France. siden.top@upmc.fr gerard.jaouen@chimie-paristech.fr.
Matthieu
M
Beauperin
Sorbonne Universités, UPMC Univ Paris 6, UMR 8232, IPCM, F-75005 Paris, France and CNRS, UMR 8232, IPCM, F-75005 Paris, France. siden.top@upmc.fr gerard.jaouen@chimie-paristech.fr.
Siden
S
Top
Sorbonne Universités, UPMC Univ Paris 6, UMR 8232, IPCM, F-75005 Paris, France and CNRS, UMR 8232, IPCM, F-75005 Paris, France. siden.top@upmc.fr gerard.jaouen@chimie-paristech.fr.
Marie-Aude
MA
Richard
University of Lodz, Faculty of Chemistry, Department of Organic Chemistry, ul. Tamka 12, Lodz 91-403, Poland.
Damian
D
Plażuk
Sorbonne Universités, UPMC Univ Paris 6, UMR 8232, IPCM, F-75005 Paris, France and CNRS, UMR 8232, IPCM, F-75005 Paris, France. siden.top@upmc.fr gerard.jaouen@chimie-paristech.fr and PSL, Chimie ParisTech, 11 rue Pierre et Marie Curie, F-75005 Paris, France.
Pascal
P
Pigeon
Faculty of Natural Sciences, Comenius University, SK-84215 Bratislava, Slovakia.
Stefan
S
Toma
Faculty of Natural Sciences, Comenius University, SK-84215 Bratislava, Slovakia.
Viera
V
Poláčková
Sorbonne Universités, UPMC Univ Paris 6, UMR 8232, IPCM, F-75005 Paris, France and CNRS, UMR 8232, IPCM, F-75005 Paris, France. siden.top@upmc.fr gerard.jaouen@chimie-paristech.fr and PSL, Chimie ParisTech, 11 rue Pierre et Marie Curie, F-75005 Paris, France.
Gérard
G
Jaouen
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D000075163:Metallocenes / Q000737:chemistry* / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D000075163:Metallocenes