33731-40-7Relevant articles and documents
Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
Beltran-Hortelano, Iván,Atherton, Richard L.,Rubio-Hernández, Mercedes,Sanz-Serrano, Julen,Alcolea, Verónica,Kelly, John M.,Pérez-Silanes, Silvia,Olmo, Francisco
, (2021/07/14)
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline.
Visible-Light-Driven Cleavage of C?O Linkage for Lignin Valorization to Functionalized Aromatics
Lin, Jinchi,Wu, Xuejiao,Xie, Shunji,Chen, Liangyi,Zhang, Qinghong,Deng, Weiping,Wang, Ye
, p. 5023 - 5031 (2019/12/02)
Lignin is the most abundant source of renewable aromatics. Catalytic valorization of lignin into functionalized aromatics is attractive but challenging. Photocatalysis is a promising sustainable approach. The strategies for designing well-performing photocatalysts are desired but remain limited. Herein, a facile energy band engineering strategy for promoting the photocatalytic activity of zinc–indium–sulfide (ZnmIn2Sm+3) for cleavage of the lignol β-O-4 bond under mild conditions was developed. The energy band structure of ZnmIn2Sm+3 could be tuned by controlling the atomic ratio of Zn/In. It was found that Zn4In2S7 performed best for cleavage of the β-O-4 bond under visible-light irradiation, owing to its appropriate energy band structure for offering adequate visible-light absorption and suitable redox capability. Functionalized aromatic monomers with near 18.4 wt % yield could be obtained from organosolv birch lignin. Mechanistic studies revealed that the β-O-4 bond was efficiently cleaved mainly through a one-step redox-neutral pathway via a Cα radical intermediate. The thiol groups on the surface of Zn4In2S7 played a key role in cleavage of the β-O-4 bond.
Visible-Light-Driven Self-Hydrogen Transfer Hydrogenolysis of Lignin Models and Extracts into Phenolic Products
Luo, Nengchao,Wang, Min,Li, Hongji,Zhang, Jian,Hou, Tingting,Chen, Haijun,Zhang, Xiaochen,Lu, Jianmin,Wang, Feng
, p. 4571 - 4580 (2017/07/24)
Obtaining high selectivity of aromatic monomers from renewable lignin has been extensively pursued but is still unsuccessful, hampered by the need to efficiently cleave C-O/C-C bonds and inhibit lignin proliferation reactions. Herein, we report a transfer hydrogenolysis protocol using a heterogeneous ZnIn2S4 catalyst driven by visible light. In this process, alcoholic groups (CαH-OH) of lignin act as hydrogen donors. Proliferation of phenolic products to dark substances is suppressed under visible light illumination at low temperature (below 50 °C); formation of a light and transparent reaction solution allows visible light to be absorbed by the catalyst. With this strategy, 71-91% yields of phenols in the conversion of lignin β-O-4 models and a 10% yield of p-hydroxyl acetophenone derivatives from organosolv lignin are achieved. Mechanistic studies reveal that CαH-OH groups of lignin β-O-4 linkage are initially dehydrogenated on ZnIn2S4 to form a "hydrogen pool", and the adjacent Cβ-O bond is subsequently hydrogenolytically cleaved to two monomers by the "hydrogen pool". Thus, the dehydrogenation and hydrogenolysis reaction are integrated in one-pot with lignin itself as a hydrogen donor. This study shows a promising way of supplying phenolic compounds by taking advantages of both renewable biomass feedstocks and photoenergy.
