Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane.
A series of platinum complexes derived from integrating demethylcantharidin (DMC) with different isomers of 1,2-diaminocyclohexane (DACH) has been synthesized and found to exhibit superior in vitro anticancer activity against colorectal and human hepatocellular cancer cell lines when compared with oxaliplatin, cisplatin, and carboplatin. Flow cytometric analysis revealed that the trans-DACH-Pt-DMC analogues showed similar behavior to oxaliplatin on affecting the cell cycle of the HCT116 colorectal cancer cell line, but distinct from that of cisplatin or carboplatin. The DACH component apparently dictates the trans-DACH-Pt-DMC complexes to behave mechanistically similar to oxaliplatin, whereas the DMC ligand appears to enhance the compounds' overall anticancer activity, probably by accelerating the cell cycle from G1 to S-phase with subsequent onset of G2/M arrest and accompanying apoptosis.
Yu
Chun-Wing
CW
School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Li
Kay K W
KK
Pang
Siu-Kwong
SK
Au-Yeung
Steve C F
SC
Ho
Yee-Ping
YP
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002193:Cantharidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D016190:Carboplatin / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003514:Cyclohexylamines / Q000737:chemistry* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D007536:Isomerism; D008113:Liver Neoplasms / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010984:Platinum / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009944:Organoplatinum Compounds; C464435:demethylcantharidin; D000077150:Oxaliplatin; D010984:Platinum; D016190:Carboplatin; C030435:1,2-cyclohexanediamine; D002193:Cantharidin; D002945:Cisplatin