Synthesis and Characterization of Griseofulvin Derivatives as Microtubule?Stabilizing Agents

Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty-seven novel griseofulvin derivatives. Three these compounds had GI50 values <10 ?M (5.74 9.7 ?M) in breast cell line CAL-51. The most promising compound ((2S,6’R)-4’-(benzhydrylamino)-7-chloro-4,6-dimethoxy-6’-methyl-3H-spiro[benzofuran-2,1’-cyclohexan]-3’-ene-2’,3-dione), was characterized as microtubule-stabilizing agent value 5.74±1.43 compared 10.79±3.06 for parental griseofulvin. It also inhibited proliferation other lines, including KB-3-1 HCT116, 1.19±0.34 2.48±0.40 ?M, respectively. Treatment cells it resulted aberrant mitosis causing G2/M arrest. Finally, show that this increased expression p53 protein induced apoptotic death.