26648-11-3Relevant articles and documents
Antitumor activity of a novel dual functional podophyllotoxin derivative involved PI3K/AKT/ mTOR pathway
Li, Yongli,Huang, Tengfei,Fu, Yun,Wang, Tingting,Zhao, Tiesuo,Guo, Sheng,Sun, Yanjie,Yang, Yun,Li, Changzheng
, (2019)
The progression of cancer through local expansion and metastasis is well recognized, but preventing these characteristic cancer processes is challenging. To this end, a new strategy is required. In this study, we presented a novel dual functional podophyl
Copper ion attenuated the antiproliferative activity of di-2-pyridylhydrazone dithiocarbamate derivative; however, there was a lack of correlation between ROS generation and antiproliferative activity
Wang, Tingting,Fu, Yun,Huang, Tengfei,Liu, Youxun,Wu, Meihao,Yuan, Yanbin,Li, Shaoshan,Li, Changzheng
, (2016)
The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying molecular mechanism are required. In this study, di-2-pyridylhydrazone dithiocarbamate S-propionic acid (DpdtpA) and its copper complex were prepared and characterized, and its antiproliferative activity was evaluated. The proliferation inhibition assay showed that DpdtpA exhibited excellent antiproliferative effect in hepatocellular carcinoma (IC50 = 1.3 ± 0.3 μM for HepG2, and 2.5 ± 0.6 μM for Bel-7402). However, in the presence of copper ion, the antiproliferative activity of DpdtpA was dramatically attenuated (20-30 fold) owing to the formation of copper chelate. A preliminarily mechanistic study revealed that reactive oxygen species (ROS) generation mediated the antiproliferative activity of DpdtpA, and accordingly induced apoptosis, DNA cleavage, and autophagy. Surprisingly, the cytotoxicity of DpdtpA copper complex (DpdtpA-Cu) was also involved in ROS generation; however, a paradoxical relation between cellular ROS level and cytotoxicity was observed. Further investigation indicated that DpdtpA could induce cell cycle arrest at the S phase; however, DpdtpA-Cu lacked this effect, which explained the difference in their antiproliferative activity.
Novel Cu(II) Schiff Base Complex Combination with Polymyxin B/Phenylalanine-Arginine β-Naphthylamide Against Various Bacterial Strains
Cheong, Siew Lee,Fong, Kar Wai,Gan, Wei Khang,Liew, Hui Shan,Liew, Yun Khoon,Low, May Lee,Ng, Xiao Ying,Pua, Lesley Jia Wei
, (2022/01/31)
Concerns on increasing trends of multidrug resistance (MDR) around the world have triggered the need to investigate and develop new therapeutic strategies and potent antibacterial drugs. Polymyxins, a class of polycationic antimicrobial peptides, have been regarded as the last-line therapy against Gram-negative bacteria due to limited new antibiotics and phenylalanine-arginine β-naphthylamide (PAβN), a peptidomimetic compound has been characterised as an efflux pump inhibitor (EPI) that have been investigated to overcome efflux-mediated multidrug resistance. In this work, the antibacterial activity of two Schiff base ligands derived from the condensation of S-benzyl dithiocarbazate with 4-carboxybenzaldehye (SB4CB) and 4-formyl-3-hydroxybenzoic acid (SBFH) their copper(II) complexes (Cu(SB4CB)2 and Cu(SBFH)2) were tested individually, and the most promising compound was tested in combination with polymyxin B (POLY) and PAβN against different bacteria, such as antibiotic-susceptible strains: Acinetobacter baumannii ATCC 19606, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 35923; multidrug-resistant strains: A. baumannii ATCC BAA-1797, E. coli BAA-196, P. aeruginosa ATCC BAA-2108 and S. aureus ATCC 43300. Initial minimum inhibition concentration (MIC) results showed the Cu(II) complexes Cu(SB4CB)2 and Cu(SBFH)2, demonstrated obvious antibacterial activity as compared to the ligand alone. Fractional inhibitory concentration (FIC) index showed improved MIC values with additivity and synergistic effect for Cu(SBFH)2 in combination with POLY and PAβN. From the in silico molecular docking investigation, Cu(SBFH)2 was shown to engage in hydrophobic interactions via its phenyl rings with surrounding hydrophobic residues in the binding pocket of S. aureus NorA, E. coli AcrB, P. aeruginosa MexB and A. baumannii AdeB efflux pumps. The phenyl rings of the ligand could also form π-π stacking with adjacent residues in the binding site of A. baumannii AdeB. Besides, hydrogen bonding and π-cation interactions were also observed via the carboxyl group, hydroxyl group and phenyl ring of SBFH moiety, respectively with nearby residues in the E. coli AcrB binding pocket. This study indicates that the combination strategy of Cu(SBFH)2 with POLY and PAβN enhances therapeutic potential and sheds light on the binding pockets inside bacteria efflux pumps and the binding interactions of ligand in the binding site.
OXADIAZOLE LINKERS AND USE THEREOF
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Page/Page column 38; 41-42, (2019/01/30)
Provided is oxadiazole linkers and use thereof, more specifically to the compounds represented by formulas (I), (II), and (III), and their use in the preparation of antibody-drug conjugates (ADCs). The ADCs obtained from said oxadiazole linkers have high homogeneity and stability, and could be used effectively for the treatment of various diseases including tumors. The definition of the groups in formula (I), (II), and (III) is the same as that in the description.
