Discovery of a Potent Importin Inhibitor for Cancer Treatment DOI
Dirk Trauner, Xiang Ji

Synfacts, Journal Year: 2022, Volume and Issue: 18(12), P. 1369 - 1369

Published: Nov. 17, 2022

Key words importin inhibitors - castration-resistant prostate cancer (CRPC) daphnane diterpenoids (DDs)

Language: Английский

Malbrumpenoids A-N, unusually cyclized triterpenoids from the Euphorbia endophyte Malbranchea umbrina D16 DOI
Shuqi Wu, Xinying Zhu, Fang-Yu Yuan

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111336 - 111336

Published: May 1, 2025

Language: Английский

Citations

0
Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1 DOI
Wei Ge,

Weikang Ming,

Zhenkun Li

et al.

Journal of Natural Products, Journal Year: 2024, Volume and Issue: 87(2), P. 276 - 285

Published: Jan. 22, 2024

Rocaglaol, embedding a cyclopenta[b]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, drug-like properties these compounds are poor. To improve physicochemical rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed synthesized. These tested for inhibitory effects on three tumor cell lines, HEL, MDA-231, SW480, using MTT assay. Among them, 22 good cytotoxic activities with IC50 values between 0.11 ± 0.07 0.88 0.02 μM. Fourteen stronger cytotoxicity than positive control, adriamycin. In particular, water-soluble derivative revealed selective HEL cells (IC50 = 0.19 0.01 μM). This compound could induce G1 cycle arrest apoptosis in cells. Western blot assays suggested that downregulate expression marker proteins apoptosis, PARP, caspase-3, caspase-9, thus inducing apoptosis. Further CETSA studies implied this might be an inhibitor friend leukemia integration 1 (Fli-1). may serve as potential antileukemia agent by suppressing Fli-1.

Language: Английский

Citations

3
13-oxyingenol dodecanoate derivatives induce mitophagy and ferroptosis through targeting TMBIM6 as potential anti-NSCLC agents DOI
Yaxu Wang, Liwei Gu,

Jichong Li

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 270, P. 116312 - 116312

Published: March 24, 2024

Language: Английский

Citations

3
Asymmetric Construction of the Core of C6, C7-Epoxy Daphnane Diterpenoid Orthoesters DOI

Ying Sun,

Jing Feng, Song Qin

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(45), P. 8072 - 8076

Published: Nov. 2, 2023

Asymmetric construction of the core C6, C7-epoxy daphnane diterpenoid orthoesters is developed through a convergent synthetic strategy. The salient features include diastereoselective nucleophilic assembly two bulky cyclic fragments, an oxidative cleavage/transesterification/aldol cascade to fashion seven-membered ring, and base-mediated transesterification/retro-aldol/aldol/epoxidation install epoxy moiety with proper stereochemistry.

Language: Английский

Citations

5
Euphylonoids A and B, Two Highly Modified Jatrophane Diterpenoids with Potent Lipid-Lowering Activity from Euphorbia hylonoma DOI
Shuqi Wu, Run‐Zhu Fan,

Fang-Yu Yuan

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(48), P. 8854 - 8858

Published: Nov. 29, 2022

Euphylonoids A (1) and B (2), two highly modified jatrophane diterpenoids, were isolated from Euphorbia hylonoma. 1 represents a new 9(10→18)-abeo-8,12-cyclojatrophane skeleton containing cage-like 3,8-dioxatricyclo[5.1.2.04,9]decane core, while 2 is 14(13→20)-abeo-8,12-cyclojatrophane featuring an unusual 17-oxatetracyclo[12.2.1.01,5.09,13]heptadecane framework. Their structural elucidation was completed by spectroscopic, chemical, computational, single-crystal X-ray diffraction means. significantly inhibited early adipogenesis in 3T3-L1 adipocytes via activating AMP-activated protein kinase signaling.

Language: Английский

Citations

8
Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer DOI Creative Commons

Jia-Luo Huang,

Xue-Long Yan,

Dong Huang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(12), P. 4934 - 4944

Published: July 25, 2023

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack druggable inhibitors restricts therapeutic proof concept. In present work, we optimized a natural inhibitor DD1 to afford improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. inhibited survival castration-resistant prostate cancer (CRPC) cells sub-nanomolar potency completely prevented tumor growth resistant CRPC models both monotherapy (0.5 mg/kg) enzalutamide-combination therapy. Mechanistic study revealed that targeting importin-β1, markedly nuclear accumulation multiple drivers, particularly AR-V7, main contributor enzalutamide resistance, leading integral suppression downstream oncogenic signaling. This provides promising lead for demonstrates potential overcoming drug resistance advanced via importin-β1.

Language: Английский

Citations

4
Daphnepedunins G and H, anti-HIV macrocyclic 3,4-seco-daphnane orthoesters from Daphne pedunculata DOI

Lingjian Tan,

Kouharu Otsuki, Mi Zhang

et al.

Journal of Natural Medicines, Journal Year: 2023, Volume and Issue: 78(1), P. 114 - 122

Published: Sept. 15, 2023

Language: Английский

Citations

4
Chemical constituents of Penicillium ferraniaense GE-7 and their cytotoxicities DOI
Yan Wang,

Shaohua Song,

Leiming Wu

et al.

Natural Product Research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 8

Published: March 4, 2024

Phytochemical investigation on the plant endophytic fungus Penicillium ferraniaense GE-7 led to isolation of 18 compounds including one new α-pyrone derivative, peniferranige A (1). The structure absolute configuration compound 1 was elucidated by NMR, HRMS, and ECD data. Demethoxyfumitremorgin C (16) meleagrin (17) possessed moderate activities against human lung cancer cell line H1975 with IC50 values 28.52 ± 1.07 13.94 1.92 μM, respectively.

Language: Английский

Citations

1
Targeting KPNB1 with Genkwadaphnin suppresses gastric cancer progression through the Nur77-mediated signaling pathway DOI
Chenxi Zhang,

Xiaojuan Wang,

Guodi Cai

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 977, P. 176697 - 176697

Published: May 31, 2024

Language: Английский

Citations

1
Diterpenoids from the Aerial Parts of Isodon serra with Selective Cytotoxic Activity DOI Creative Commons

Siqin Li,

Liang Fang,

Dongdong Huang

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2733 - 2733

Published: June 8, 2024

Four new diterpenoids, isodosins A–D (1–4), together with nine known compounds (5–13) were isolated and identified from the aerial parts of Isodon serra (Maxim.) Hara. The structures diterpenoids elucidated based on analysis HR-ESI-MS data, 1D/2D-NMR-spectroscopic electronic circular dichroism (ECD) calculations. Cytotoxicities 2, 3, 5, 6, 9 against HepG2 H1975 cell lines evaluated MTT assay. As a result, 6 revealed higher levels cytotoxicity cells than cells. Moreover, compund demonstrated most efficacy in inhibiting proliferation cells, an IC50 value 41.13 ± 3.49 μM. This effect was achieved by inducing apoptosis dose-dependent manner. Furthermore, relationships between activities these are briefly discussed.

Language: Английский

Citations

1