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Keywords = lignohydroquinones

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22 pages, 5631 KiB  
Article
Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells
by Ángela-Patricia Hernández, Paula Díez, Pablo A. García, Martín Pérez-Andrés, Anzhela Veselinova, Pablo G. Jambrina, Arturo San Feliciano, David Díez, Manuel Fuentes and Mᵃ Ángeles Castro
Pharmaceutics 2023, 15(3), 886; https://doi.org/10.3390/pharmaceutics15030886 - 9 Mar 2023
Cited by 5 | Viewed by 2426
Abstract
New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates [...] Read more.
New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic linkers. Among the evaluated hybrids, the L-HQ with the aromatic spacer clearly displayed the in vitro dual cytotoxic effect derived from each starting component, retaining the selectivity and showing a high cytotoxicity at short (24 h) and long (72 h) incubation times (4.12 and 0.0450 µM, respectively) against colorectal cancer cells. In addition, the cell cycle blockade observed by flow cytometry studies, molecular dynamics, and tubulin interaction studies demonstrated the interest of this kind of hybrids, which docked adequately into the colchicine binding site of tubulin despite their large size. These results prove the validity of the hybridization strategy and encourage further research on non-lactonic cyclolignans. Full article
(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)
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