| Abstract
| - In our previous study, neo-tanshinlactone (1) showed potent and selective anti-breast cancer activity. Toexplore the SAR of 1, nine analogues (15−18, 24−28) were designed and synthesized. Together with 1 andtamoxifen (TAM), all newly synthesized compounds and some intermediates were evaluated for in vitroanticancer activity against several human tumor cell lines. Compounds without a ring D did not showpromising activity, while compounds with a methylated furan ring D showed better activity than those withunsubstituted furan or hydroxy-dihydrofuran rings. Among all newly synthesized compounds, compound15 with an ethyl group at the 4-position showed the best activity and selectivity with ED50 values of 0.45and 0.18 μg/mL against MCF-7 and ZR-75-1 (ER+) and 13.5 and 10.0 μg/mL against MDA MB-231 andHS 587-1 (ER−), respectively. Furthermore, 15 also showed potent activity against SK-BR-3 (ER−, HER2+)with an ED50 value of 0.10 μg/mL. Our preliminary SAR studies showed that a methylated furan ring D andthe C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 asanti-breast cancer drug candidates is warranted.
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