Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 6; pp. 1686 - 1691
• Main Authors: Yu, Chun-Wing, Li, Kay K.W., Pang, Siu-Kwong, Au-Yeung, Steve C.F., Ho, Yee-Ping
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.03.2006; Elsevier
• Subjects: 1,2-Diaminocyclohexane; Anticancer agents; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cantharidin - analogs & derivatives; Cantharidin - chemistry; Cantharidin - metabolism; Carboplatin - pharmacology; Carcinoma, Hepatocellular - drug therapy; Cell cycle; Cell Cycle - drug effects; Cisplatin - pharmacology; Colorectal Neoplasms - drug therapy; Cyclohexylamines - chemistry; Cyclohexylamines - metabolism; Demethylcantharidin; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Flow Cytometry; General aspects; Humans; Isomerism; Liver Neoplasms - drug therapy; Medical sciences; Organoplatinum Compounds - pharmacology; Pharmacology. Drug treatments; Platinum - chemistry; Platinum - metabolism; Tumor Cells, Cultured - drug effects; 1,2-Diaminocyclohexane; Anticancer agents; Demethylcantharidin; Cell cycle; Antineoplastic agent; Human; Platinum Complexes; Colorectal cancer; Organic ligand; Oxygen heterocycle; In vitro; Cell line; Structure activity relation; Bicyclic compound; Colon; Mechanism of action; Chemical synthesis; Antimitotic; Tumor cell; Apoptosis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.12.019

Anticancer activity and flow cytometric analysis of a series of trans-DACH–Pt–DMC analogues are compared with those of oxaliplatin, cisplatin, and carboplatin. 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.