Hybridization of nitric oxide (NO) donors with known anti-cancer agents have been emerged as a strategy to achieve improved therapeutic effect and to overcome chemo-resistance in cancer therapy. In this study, furoxan moiety as an efficient NO donor was introduced to phenstatin, a microtubule-interfering agent (MIA), leading to the design and synthesis of a series of furoxan-based NO-releasing arylphenones derivatives. In biological evaluation, the synthesized compounds showed moderate to potent anti-tumor activities against several human cancer cell lines. Among them, compound 15h showed the most potent activities against both chemo-sensitive and resistant cancer cell lines with IC
