کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1397387 | 1501141 | 2014 | 14 صفحه PDF | دانلود رایگان |
• Novel flavonoids based 4-tosyloxy, 4-hydroxy and 4-cinnamoyl THPs were synthesized.
• Compounds 3a, 3f, 3q, 3s and 3zb showed good to moderate cytotoxicity against the MCF-7 cells.
• Compounds 3c, 3zb showed good cytotoxicity against the Hep3β cells.
• Compounds 3c and 3q showed good cytotoxicity against the HeLa cells.
Following our previously reported Prins cyclization strategy, a series of novel and highly functionalized flavonoid based THPs (Prins products) were designed, synthesized and evaluated for their antiproliferative activity. Novel products were afforded in excellent yields (72–96%) within 20–90 min at 62 °C using flavonoid aldehydes, homoallylic alcohols, p-TSA·H2O (catalyst and reagent) and MS 4 Å in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 °C to obtain 4-hydroxytetrahydropyrans and further reaction of 4-hydroxytetrahydropyrans with cinnamoyl chloride afforded 4-cinnamate tetrahydropyrans under neat condition. Synthesized compounds evaluated against human cancer cell lines (Hep3β, MCF-7 and Hela), have shown moderate to good antiproliferative activity in vivo. Compounds 3q and 3zb exhibited similar cytotoxicity (IC50 6.6 ± 1.4, 6.9 ± 1.0 μM, respectively) to the reference drug doxorubicin (IC50 7.6 ± 0.9 μM) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 ± 2.1 μM) against the Hep3β cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 ± 1.1, 12.9 ± 1.7 μM, respectively) against the HeLa cell line.
Flavonoid–THP conjugates were synthesized and screened for their antiproliferative activity. Compounds 3q and 3zb have shown similar cytotoxic activity (IC50 6.6 ± 1.4, 6.9 ± 1.0 μM respectively) as doxorubicin (IC50 7.6 ± 0.9 μM) against the MCF-7. Compound 3zb showed excellent cytotoxicity against the Hep3β cells.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 75, 21 March 2014, Pages 233–246