Syntheses and Cytotoxic Properties of the Curcumin Analogs 2,6-Bis(benzylidene)-4-phenylcyclohexanones

• Published in: Archiv der Pharmazie (Weinheim) 2008-07, Vol.341 (7), p.440-445
• Main Authors: Davis, Ryan, Das, Umashankar, Mackay, Hilary, Brown, Toni, Mooberry, Susan L., Dimmock, Jonathan R., Lee, Moses, Pati, Hari
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; B16; Cell Line, Tumor; Curcumin - analogs & derivatives; Curcumin analogs; Cyclohexanones - administration & dosage; Cyclohexanones - chemical synthesis; Cyclohexanones - pharmacology; Drug Screening Assays, Antitumor; Inhibitory Concentration 50; L1210; Mice; Microtubules; Microtubules - drug effects; Quantitative Structure-Activity Relationship; Structure-activity relationships; Tubulin - drug effects
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.200800028

Fifteen curcumin analogs were synthesized and tested for in‐vitro cytotoxicity towards B16 and L1210 murine cancer cell lines using an MTT assay. Significant activity was discovered for two analogs: 8 (B16 IC50 = 1.6 μM; L1210 IC50 = 0.35 μM) and 9 (B16 IC50 = 0.51 μM; L1210 IC50 = 1.2 μM). Several other analogs exhibited notable cytotoxicity. The data from quantitative structure‐activity relationships suggest that large electron‐withdrawing substituents placed in the meta‐position of the arylidene aryl rings enhance potencies. Compounds 8 and 9 were found using a cell‐based assay to have virtually no effects on microtubules at concentrations up to 40 μM. These results suggest that tubulin inhibition is not the principal mechanism by which the curcumin analogs act.