作者: Arbe, Maria Florencia ; Glikin, Gerardo Claudio ; Salamone, Gabriela Veronica ; Finocchiaro, Liliana María Elena ; Villaverde, Marcela Solange ; Pan, Melisa Denise

Despite encouraging advances during the last decade, clinical management of malignant human, canine and feline melanoma continues to be a challenge. Thus, new therapeutic development is required. One of the hallmarks of cancer is metabolic rearrangement, including increased glucose metabolism. This metabolic alteration seems to be involved not only in cell proliferation but also in drug resistance, thus offering potential therapeutic targets. The aim of the present work was to investigate the in vitro effects of a combination of metformin (MET, an antidiabetic drug and OXPHOS inhibitor), 2-deoxyglucose (2DG, an HK inhibitor) and 6-aminonicotinamide (6AN, a G6PDH inhibitor) on two melanoma cell lines, Sc (canine) and Dc (feline) derived from spontaneous tumors. We found that both 2DG and MET treatment significantly decreased the cell viability of both cell lines (p < 0.05) in a concentration-dependent manner, whereas 6AN as monotherapy only significantly affected Sc. In addition, the effect of MET was significantly potentiated (p < 0.05) by the combination with both 2DG and 6AN in both cell lines. MET/2DG and MET/6AN significantly affected the cell cycle and increased the percentage of the subG0 population. These results support further studies to investigate the potential use of these metabolic drugs in a veterinary clinical setting.

2024-10-23·JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Design, Synthesis, and Herbicidal Activities of N-(5-(3,5-Methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide Derivatives

Article

作者: Li, Hao ; Wang, Yingying ; Han, Jincai ; Li, Zuren ; Wan, Yuanhui ; Liu, Na ; Luo, Dingfeng ; Bai, Haodong ; Bai, Zhendong ; Bai, Lianyang

Thiazole and phenoxyacetic acid are key moieties in many natural and synthetic biologically active agents. A series of N-(5-(3,5-methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide derivatives 6an-6bd were designed and synthesized, and their structures were confirmed by NMR and HRMS. Most of derivatives exhibited superior inhibition of Echinochloa crusgalli (E.c.) and Lactuca sativa (L.s.) seed germination by the Petri dish bioassay. Indeed, herbicidal bioassays indicated that 6an (2-(2,4-dichlorophenoxy)-N-(5-(3,5-dimethoxyphenyl)-1,3,4-thiadiazol-2-yl)acetamide) had the best inhibition against L.s. (IC₅₀ = 42.7 g/ha, 375 g/ha at field experiments). 6an also had no harmful effect on Zea mays at 2- to 4-fold field usage. Moreover, transcriptomics and metabolomics analysis showed that 6an significantly influenced cell metabolism, including galactose metabolism and ascorbate and aldarate metabolism. These discoveries highlight that 6an shows promise to be developed as a potential herbicide.

2023-06-01·Cellular and molecular life sciences : CMLS

G6PD activation in TNBC cells induces macrophage recruitment and M2 polarization to promote tumor progression

Article

作者: Wang, Changjun ; Sun, Qiang ; Li, Chenggang ; Han, Xiao ; Fu, Zhenkun ; Lin, Zhoujun ; Li, Yin

Glucose-6-phosphate dehydrogenase (G6PD) is involved in triple-negative breast cancer (TNBC) progression. Metabolic crosstalk between cancer cells and tumor-associated macrophages mediates tumor progression in TNBC. Molecular biological methods were applied to clarify the mechanism of the crosstalk between TNBC cells and M2 macrophages. In the present study, we verified that G6PD overexpression drives M2 macrophage polarization by directly combining with phospho-STAT1 and upregulating CCL2 and TGF-β1 secretion in TNBC cells. In turn, M2-like TAMs activated TNBC cells through IL-10 secretion, providing feedback to upregulate G6PD and promote TNBC cell migration and proliferation in vitro. Furthermore, we found that 6-AN (a specific inhibitor of G6PD) not only suppressed the cancer-driven polarization of macrophages toward the M2 phenotype but also inhibited the inherent M2 polarization of macrophages. Targeting the G6PD-regulated pentose phosphate pathway restrained TNBC progression and M2-type polarization of macrophages in vitro and in vivo.

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适应症	最高研发状态	国家/地区	公司	日期
KRAS突变非小细胞肺癌	药物发现	澳大利亚	The Walter & Eliza Hall Institute of Medical Research	2019-09-13
KRAS突变非小细胞肺癌	药物发现	澳大利亚	University of Melbourne	2019-09-13
KRAS突变非小细胞肺癌	药物发现	荷兰	Netherlands Cancer Insitute	2019-09-13