Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response

Article

作者: Xu, Gang ; Li, Wenjuan ; Yang, Feng ; Liang, Jinzhe ; Liang, Hong ; Li, Shanhe ; Pang, Min ; Zhang, Zhenlei ; Zhu, Minghui ; Jiang, Ming

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on a specific residue of human serum albumin (HSA) for multiacting on tumor cell and other components in the tumor microenvironment. To this end, a series of Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized to obtain a Pd(II) compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, we constructed a HSA-5b complex delivery system and revealed the structural mechanism of HSA delivering 5b. Importantly, 5b/HSA-5b effectively inhibited the growth and metastasis of multidrug resistant liver tumors, and HSA enhanced the targeting ability of 5b and reduced its side effects in vivo. Furthermore, we confirmed the mechanisms of 5b/HSA-5b integrating to overcome MDR and metastasis of liver tumors: multiacting on cancer cell, activating immune response, and inactivating cancer-associated fibroblasts.

2024-06-02·Natural Product Research

Preparation and antibacterial activity of coronarin E derivatives

Article

作者: Qin, Jie-Chen ; Tuo, Cheng-Jie ; Zhao, Qing ; Liu, Meng-Yujie ; Zhang, Xiao-Mei ; Zhang, Ke-Tao ; Liu, Chao-Jin

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense. With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a, 4b, 5a and 5b) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a, 5b, ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 μg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 μg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines.

2024-04-01·Bioorganic & Medicinal Chemistry Letters

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation

Article

作者: Abdel-Aziz, Mohamed ; Konno, Hiroyuki ; Shoman, Mai E ; Soltan, Osama M ; Narumi, Atsushi ; Abdel-Aziz, Salah A ; Osawa, Keima ; Sh Shaykoon, Montaser

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC₅₀) values of 2.7-63 μM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC₅₀ of 2.0 and 0.9 μM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC₅₀ = 1.7 μM). Notably, 6c inhibited both kinases, with IC₅₀ values of 2.7 and 3.0 μM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

100 项与 Foxy-5B 相关的药物交易

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