Novel Nitric Oxide Donors of Phenylsulfonylfuroxan and 3-Benzyl Coumarin Derivatives as Potent Antitumor Agents

Abstract

In this work, five new hybrids of phenylsulfonylfuroxan merging 3-benzyl coumarin and their seco-B-ring derivatives <b>2</b>-<b>6</b> were designed and synthesized. Among them, compound <b>3</b> showed the most potent antiproliferation activities with IC₅₀ values range from 0.5 to 143 nM against nine drug-sensitive and four drug-resistant cancer cell lines. Preliminary pharmacologic studies showed that these compounds displayed lower toxicities than that of lead compound <b>1</b>. Compound <b>3</b> obviously induced the early apoptosis and hardly affected the cell cycle of A2780, which was significantly different from compound <b>1</b>. Especially, it gave 559- and 294-fold selectivity antiproliferation activity in P-gp overexpressed drug-resistant cancer cell lines MCF-7/ADR and KB-V compared to their drug-sensitive ones MCF-7 and KB, implying that compounds <b>2</b>-<b>6</b> might have an extra mechanism of anti-MDR-cancer with P-gp overexpression.