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Updated: Jan 24, 2026

Synthesis of a Water-soluble Metal–Organic Complex Array
Published on: October 8, 2016
Design, synthesis, and biological evaluation of target water-soluble hydroxamic acid-based HDACi derivatives as
Jun Li1,2, Yedan Zhu3, Miaohong Xie1
1School of Pharmacy, Hangzhou Medical College, Hangzhou, China.
Abstract:
Four compounds T1, T2, T3, and T4 were designed and synthesized as Vorinostat and Belinostat derivatives being the target water-soluble prodrugs. The water solubility of Vorinostat derivatives, T1 and T2, exhibited 400- to 600-fold higher than that of Vorinostat, and Belinostat derivatives, T3 and T4, showed 600- to 750-fold higher than that of Belinostat. Four compounds were evaluated for their inhibitory activities against tumor cell lines HT-29 and Hut-78 in the absence or presence of β-D-glucuronidase. The inhibitory effects of T1 and T2 were comparable to Vorinostat in the presence of β-D-glucuronidase, but were higher than 10 μM in the absence of β-D-glucuronidase. Therefore, T1 and T2 are promising candidates for in vivo investigations with high potential to be the target water-soluble prodrugs. IC50 values of Belinostat derivatives T3 and T4 were not affected by β-D-glucuronidase, but T3 and T4 had the excellent cell proliferation inhibition on Hut-78.
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