Deuterated Curcuminoids : Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim..
A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR-BF2 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR-BF2 adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR-BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
ChemMedChem - 14(2019), 12 vom: 18. Juni, Seite 1173-1184 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Laali, Kenneth K [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 17.04.2020 Date Revised 17.04.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cmdc.201900179 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296159417 |
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| 520 | |a © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR-BF2 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR-BF2 adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR-BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a colorectal cancer | |
| 650 | 4 | |a curcuminoids | |
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| 700 | 1 | |a Nukaya, Manabu |e verfasserin |4 aut | |
| 700 | 1 | |a Kennedy, Gregory D |e verfasserin |4 aut | |
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