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1.
J Nat Prod ; 87(4): 884-892, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408342

RESUMEN

The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC50: 8.8 vs 5.9 µM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 µM).


Asunto(s)
Sesquiterpenos , Humanos , Estereoisomerismo , Estructura Molecular , Células Hep G2 , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/síntesis química
2.
Food Chem ; 439: 138104, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38043284

RESUMEN

Anthocyanins are natural polyphenols belonging to the flavonoid family that possess a variety of putative health benefits when consumed in a balanced diet. However, applications of anthocyanins in, for example, functional foods are limited due to poor stability, degradation, and low transmembrane efficiency. To maintain bioactivities of anthocyanins and optimize their use, various carrier materials have been developed. Here, we reviewed the uses of the different carrier materials (organic/inorganic, micro/nano) for anthocyanin encapsulation and delivery over the past five years. The performance of different materials and interactions between anthocyanins and these materials are described. Lastly, we give our perspective on the future development trend of anthocyanin encapsulation strategies.


Asunto(s)
Antocianinas , Flavonoides , Antocianinas/metabolismo , Polifenoles
3.
J Org Chem ; 88(23): 16511-16519, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37972539

RESUMEN

The first synthesis of ustusal A as well as expeditious access to (-)-albrassitriol is described as featuring a singlet oxygen [4 + 2] cycloaddition, achieving the desired stereoselectivity for the 1,4-cis-hydroxyl groups. Transformation of (+)-sclareolide to III followed by a key Horner-Wadsworth-Emmons (HWE) reaction and stereospecific allylic oxidation facilitated the first synthesis of elegansin D. The biological evaluation of these natural products together with seven elegansin D analogues was performed, among which several elegansin D analogues exhibited potential anticancer activity against liver cancer HepG2 cells (IC50 = 11.99-25.58 µM) with low cytotoxicity on normal liver HL7702 cells (IC50 > 100 µM).


Asunto(s)
Estereoisomerismo , Oxidación-Reducción
4.
Bioorg Chem ; 119: 105543, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34929515

RESUMEN

Previously, an array of N-substituted acridone derivatives have been reported as potent topoisomerase II (topo II) inhibitors, and preliminary structure-activity relationship (SAR) outcomes revealed that the linker between 1-NH and N-methyl piperazine motif of the tricyclic acridone scaffold significantly affected their anti-proliferative potencies. To further explore the SARs of acridone-derived topo II inhibitors, a wider range of novel acridone derivatives were herein synthesized via two rounds of structural optimizations on two validated hits, E17 and E24. Initially, the linker length was optimized, and then influences of N-methyl piperazinyl moiety and disposition of three N atoms on the bioactivity were investigated. As a result, a newly developed topo II inhibitor 6 h was found to be more potent than E17 and E24, thereby serving as a tool compound for the follow-up mechanistic study. Compound 6 h functioned as a strong topo IIα/ß inhibitor, caused obvious DNA damage, and induced apoptosis by triggering the loss of mitochondrial membrane potential (Δψm). Further molecular docking and MD study illustrated the favorable interactions of 6 h with both topo IIα and topo IIß subtypes.


Asunto(s)
Acridonas/farmacología , Antineoplásicos/farmacología , ADN-Topoisomerasas de Tipo II/metabolismo , Inhibidores de Topoisomerasa II/farmacología , Acridonas/síntesis química , Acridonas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/química , Células Tumorales Cultivadas
5.
Cells ; 10(11)2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34831359

RESUMEN

Type II DNA topoisomerase (topo II) is an essential nuclear enzyme and a well-validated anticancer drug target. Previously, we have carried out several rounds of structural optimizations on our in-house topo II inhibitor E17, which was shown to have superior anticancer activity and less risk of multidrug resistance (MDR). Among the newly developed acridone derivatives, 6h displayed significant anticancer efficacy with unique mechanisms of action. At low concentrations, it arrested cancer cell cycles and triggered cell apoptosis, which is similar to the action of the well-known topo II inhibitor VP16. By contrast, 6h showed significant and long-term anti-proliferative activity at relatively high concentrations, with negligible influence on apoptosis. In addition, 6h exhibited no serious cardiotoxicity compared to doxorubicin (DOXO), a widely used topo II-targeting antineoplastic drug in clinic, but with damaging myocardial side effects. Collectively, our present work has supported the therapeutic value of 6h as a promising chemotherapy for cancers.


Asunto(s)
Antineoplásicos/farmacología , Cardiotoxicidad/prevención & control , Inhibidores de Topoisomerasa II/farmacología , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Cardiotoxicidad/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Etopósido/farmacología , Humanos , Ratas , Inhibidores de Topoisomerasa II/química
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