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In a continuing study, we explored how the individual rings in neo-tanshinlactone (1) influence its potent and selective in vitro antibreast cancer activity. Accordingly, we discovered a novel class of antibreast cancer agents, 2-(furan-2-yl)naphthalen-1-ol derivatives, based on an active C-ring opened model compound 5. Further optimization led to 18and 21, which showed decreased cytotoxic potency but better selectivity than neo-tanshinlactone analogue 2. Interestingly, 20showed broad cytotoxicity against human cancer cell lines. [ABSTRACT FROM AUTHOR]