Cyclopentadienyl-ruthenium(II) and iron(II) organometallic compounds with carbohydrate derivative ligands as good colorectal anticancer agents.
New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HCT116 cell line was determined for a total of 23 organometallic compounds and SAR's data analysis within this library showed an interesting dependency of the cytotoxic activity on the carbohydrate moiety, linker, phosphane coligands, and metal center. More importantly, two compounds, 14Ru and 18Ru, matched oxaliplatin IC50 (0.45 μM), the standard metallodrug used in CC chemotherapeutics, and our leading compound 14Ru was shown to be significantly more cytotoxic than oxaliplatin to HCT116 cells, triggering higher levels of caspase-3 and -7 activity and apoptosis in a dose-dependent manner.
†Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Pedro R
PR
Florindo
‡Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Diane M
DM
Pereira
‡Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Pedro M
PM
Borralho
‡Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Cecília M P
CM
Rodrigues
†Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.|§Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
M F M
MF
Piedade
†Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Ana C
AC
Fernandes
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005296:Ferrous Compounds / Q000494:pharmacology; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry
D000970:Antineoplastic Agents; D002241:Carbohydrates; D005296:Ferrous Compounds; D008024:Ligands; D009942:Organometallic Compounds; D012428:Ruthenium