Novel indolo-sophoridinic scaffold as Topo I inhibitors: Design, synthesis and biological evaluation as anticancer agents

European Journal of Medicinal Chemistry
Yiming XuPeng Xie

Abstract

Based on the mechanism of action, novel scaffolds as Topo I inhibitors bearing indole and sophoridinine were designed. Preliminary docking study revealed that some molecules among the designed series possessed promising Topo I inhibitor properties. Subsequently, thirty new compounds were synthesized and characterized by 1H NMR, 13C NMR, and Mass spectral analyses. The compounds were then screened for their antiproliferative and enzymatic inhibitory activities. The results affirmed the consistency between docking and activities and the rationality of the design strategy. Furthermore, compound 10b was chosen as a representative compound to test its anticancer effects in vitro and in vivo. The results showed that 10b caused prominent S phase cell cycle arrest and significantly suppressed tumor growth in HepG2 cell derived mouse model. These findings present a promising series of lead molecules which can serve as potential Topo I inhibitors for the treatment of cancer and a theoretical basis for structural modifications.

Citations

Aug 20, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Ulviye Acar ÇevikZafer Asım Kaplancıklı
Apr 26, 2020·Bioorganic Chemistry·Haroon Ur RashidMarco Antonio Utrera Martines
Sep 10, 2020·Current Topics in Medicinal Chemistry·Feng SongMeng Zhou

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