Advances in metal-organic framework-based nanozymes in ROS scavenging medicine.

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.

Design, synthesis and anticancer activity of oxoaporphine alkaloid derivatives.

A series of new oxoaporphine derivatives were synthesized and their inhibitory activity of topoisomerase I, cytotoxicity and DNA-binding properties were studied. Oxoaporphine can strongly inhibit topoisomerase I at concentrations of 5-50 µM and the cytotoxicity of the derivatives are more potent than their lead compound. Hypochromism, broadening and red shift in the absorption spectra were observed when these compounds bind to calf thymus DNA (CT DNA). These spectral characteristics were consistent with the intercalative binding of these compounds.

Synthesis, characterization and anti-diabetic therapeutic potential of a new benzyl acid-derivatized kojic acid vanadyl complex.

Vanadium complexes are potent hypoglycemic agents and of great potential for therapeutical treatment of diabetes. In the present work, a novel vanadium compound, bis ((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl benzoatato) oxovanadium (IV) (BBOV) has been synthesized. Treatment of STZ-induced diabetic rats with BBOV restored the blood glucose to normal level and ameliorated glucose tolerance. The hypoglycemic effect of BBOV is similar to that of bis (maltolato) oxovanadium but is less toxic in median lethal dose. Overall, the present work will provide useful information for further development of new anti-diabetic vanadium compounds.

Oxoisoaporphine alkaloid derivatives: synthesis, DNA binding affinity and cytotoxicity.

A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1-azabenzanthrone (general formula Ar-NHCO(CH(2))(n)NR(2), Ar=1-azabenzanthrone, n=1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure-activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n=2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity.

Synthesis, biological evaluation and molecular modeling of oxoisoaporphine and oxoaporphine derivatives as new dual inhibitors of acetylcholinesterase/butyrylcholinesterase.

Aporphine alkaloids, isolated from Chinese medicinal herb, are important natural products. We recently reported that synthetic derivatives of oxoisoaporphine alkaloids exhibited high acetylcholinesterase inhibitory activity and high selectivity for AChE over BuChE (Bioorg. Med. Chem. Lett. 2007, 17, 3765-3768). In this paper, further research results were presented. A series of novel derivatives of oxoaporphine alkaloids (5a-j, 4-carboxylic amide-7-oxo-7H-dibenzo[de,g]quinoline, Ar-CONH(CH(2))(n)NR) and their quaternary methiodide salts (6a-h, Ar-CONH(CH(2))(n)N(+)(CH(3))RI(-)) were designed and synthesized as acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE) inhibitors. The AChE inhibition potency of synthetic oxoaporphine derivatives was decreased about 2-3 orders of magnitude as compared with that of oxoisoaporphine derivatives. Non-competitive binding mode was found for both kinds of derivatives. Molecular docking simulations on the oxoisoaporphine derivatives 7 series and oxoaporphine derivatives 6 series with AChE from Torpedo californica have demonstrated that the ligands bound to the dual-site of the enzyme.

Derivatives of oxoisoaporphine alkaloids: a novel class of selective acetylcholinesterase inhibitors.

A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar-NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold). The structure-activity relationships (SARs) were discussed.