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Chinese Journal of Chemistry 2022年第12期40卷 1447-1456页

作者： Jianlin Lv Yajun Xu Yue Huang Haiyang Yu Zhaohui Tang Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunJilin 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefeiAnhui 230026China Jilin Biomedical Polymers Engineering Laboratory 5625 Renmin StreetChangchunJilin 130022China

This work was supported by the National Natural Science Foundation of China(Nos.52025035,52103195).The comprehensive graphic content and graphic abstract were created with *** by coauthors.

关键词： Vascular disrupting agents antitumor agents Self-assembly Cancer Nanoparticles

Total Synthesis and Stereochemical Assignment of Talaroconvolutin A and Talarofuranone: Gram-scale Synthesis of Ferroptosis Inducer Talaroconvolutin A

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Chinese Journal of Chemistry 2024年第13期42卷 1509-1514页

作者： Ming Yao Wei Yang Jing Li Chengyun Huang Jin Fang Sulu Qin Shuzhi Liu Xiaolong Yang School of Pharmaceutical Sciences South-Central Minzu UniversityWuhanHubei 430074China

The first total synthesis of talaroconvolutin A(1.1 g obtained)and talarofuranone has been achieved using accessible materials(12 steps,7.5%and 8.2%yields,respectively).Convergent routes involved intramolecular Diels-Alder reactions in two approaches for creating the decalin ***,an unprecedented DMP-mediated domino reaction resulted in the deoxy-tetramic acid *** syntheses not only establish the absolute configuration of talaroconvolutin A but also enable further collaborative studies of this typeofferroptosisinducers.

关键词： Natural products Aldehydes Total synthesis Domino reactions Biological activity antitumor agents Ferroptosis Diels-Alder reaction Talaroconvolutin A

Cation-anionicpalladium Complexes—New Types of antitumor, Immune Response-modulating and Radioprotective agents

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贵金属 2012年第A1期33卷 240-242页

作者： EFIMENKO I.A. SHISHILOV O.N. IVANOVA N.A. EROFEEVA O.S. N.S. Kurnakov Institute of General and Inorganic Chemistry of RAS MoscowRussia

Here we report results of our investigations of new class of bioactive palladium compounds (AH n ) m [PdCl 4 ], which were discovered as a result of systematic study of correlations between composition, structure and bioactivity of different types of platinum metals coordination compounds. For the first time we demonstrated in vivoa possibility of development of palladium compounds, which exceed cisplatin in antitumor activity and do not show immunosuppressive effects, and palladium compounds with immunostimulating and radioprotective activities. Combinations of cytostatic agents or radiation with palladium complexes lead to significant synergism of their activities and high therapeutic efficiency exceeded an efficiency of their separated use.

关键词： palladium chlorides heterocyclic amines antitumor agents immune response-modulating agents radioprotective agents

Precise Control of Self-assembly in vivo Based on Polymer-Peptide Conjugates

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Chinese Journal of Chemistry 2022年第23期40卷 2815-2824页

作者： Yin-Sheng Xu Hao Wang Zeng-Ying Qiao CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST)Center of Materials Science and Optoelectronics EngineeringUniversity of Chinese Academy of SciencesBeijing 100190China

The self-assembled nanomaterials based on peptides,which have not only good biocompatibility and low toxicity but also high stability and performance,are increasingly becoming an important way for cancer *** this review,we highlight the progress of in vivo self-assembled polymer-peptide conjugates(PPCs)and their application,showing the recent advances in the development of“in vivo self-assembly”strategy for cancer *** the diverse microenvironments of tumor cells,different responsive assembly strategies(enzyme,pH,redox,temperature,etc.)have been developed to precisely control the assembly at different biological levels,realizing enhanced drug delivery and improved anticancer efficacy.

关键词： Polymer-peptide conjugates Drug design In vivo self-assembly Drug delivery antitumor agents

Photothermally Enhanced Dual Enzyme-mimic Activity of Gold-Palladium Hybrid Nanozyme for Cancer Therapy

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Chinese Journal of Chemistry 2023年第23期41卷 3189-3196页

作者： Yan Kang Chao Li Huali Shi Amin Zhang Chusen Huang Chaohui Zhou Nengqin Jia The Education Ministry Key Lab of Resource Chemistry Joint International Research Laboratory of Resource ChemistryShanghai Key Laboratory of Rare Earth Functional MaterialsCollege of Chemistry and Materials ScienceShanghai Normal University100 Guilin RDShanghai200234 China Institute of Nano Biomedicine and Engineering Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong University800 Dongchuan RDShanghai200240 China

Based on characteristics of the tumor microenvironment(TME),including acidity,hypoxia,inflammation and hydrogen peroxide overload,combined with emerging nanotechnologies,designing nanoplatforms with TME specificity/responsiveness for tumor treatment is a promising nanotherapeutic *** this work,a multifunctional gold-palladium bimetallic cascade nanozyme was constructed for effective photothermal-enhanced cascade catalyzed synergistic therapy of *** dumbbell-like Au-Pd bimetallic nanomaterial(Au NRs-Pd@HA)was obtained by reducing palladium on gold nanorods with ascorbic acid(AA)and further modified with hyaluronic acid(HA).The introduction of HA brings biocompatibility and targeting *** zebrafish embryos model showed that Au NRs-Pd@HA had good biocompatibility and low *** NRs-Pd@HA can induce catalytic conversion of glucose to generate H_(2)O_(2) efficiently,and subsequently undergo cascade reaction to produce abundant·OH radicals,exhibiting peroxidase-like(POD-like)and glucose oxidase-like(GOD-like)*** generated·OH was a key factor for tumor ***,Au NRs-Pd@HA exhibits good photothermal performance under 808 nm irradiation,in favor of photothermal therapy(PTT).Especially,the POD-like and GOD-like activities were significantly enhanced due to the photothermal *** synergistic PTT and photothermal-enhanced nanozymes with cascade catalytic effect enabled efficient and safe cancer therapy.

关键词： Nanozymes catalyzed therapy Photothermal therapy Cascade catalytic Good biocompatibility Cancer antitumor agents Catalytic therapy

In silico design of anti-tumor mini-protein targeting MDM2

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Chinese Chemical Letters 2023年第5期34卷 256-258页

作者： Jinghui Zhang Huixin Xu Baishi Wang Xuekai Zhang Lei Fu Yannan Li Guanzhao Wu Zitong Zhao Lu Liu Ting Yang Zheyu Zhang Jinbo Yang Tao Jiang Peiju Qiu Rilei Yu Key Laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology Qingdao 266237China Innovation Center for Marine Drug Screening&Evaluation Pilot National Laboratory for Marine Science and Technology(Qingdao) Qingdao 266003China Department of Biological Engineering College of Chemical and Biological EngineeringShandong University of Science and TechnologyQingdao 266590China

We designed a disulfide-crosslinked mini-protein with a two-helical topology consisting of L-and Damino acids,which was exceptionally stable in ***,we further used it as a scaffold to design mini-proteins targeting p53 positive tumor *** on bifunctional grafting,key residues from the transactivation domain of p53 and a designed unnatural amino acid were grafted into the helix constituted by L-amino acids to confer the mini-protein with MDM2 inhibitory ***,ten Arg residues were introduced to improve its membrane penetrating *** the mini-proteins,UPROL-10e showed nano-molar binding affinity on MDM2 and cellular toxicity on p53 expressing HCT116cells.

关键词： Protein design antitumor agents In silico design Constrained peptide Epitope grafting

Epigallocatechin-3-gallate Modulates MicroRNA Expression Profiles in Human Nasopharyngeal Carcinoma CNE2 Cells

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Chinese Medical Journal 2017年第1期130卷 93-99页

作者： Bin-Bin Li Guo-Liang Huang Hua-Hui Li Xia Kong Zhi-Wei He Department of Pathophysiology Guangdong Medical University Dongguan Guangdong 523808 China Sino-American Cancer Research Institute Key Laboratory for Medical Diagnostics of Guangdong Province Guangdong Medical University Dongguan Guangdong 523808 China

Background： Epigallocatechin-3-gallate （EGCG） has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma （NPC）, but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs （miRNAs） in NPC cells. Methods： Using microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis. Results： A total of 14 miRNAs exhibited 〉2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs. Conclusion： EGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

关键词： antitumor agents Epigallocatechin-3-gallate MicroRNAs Nasopharyngeal Carcinoma

Design, Synthesis and Preliminary Biological Evaluation of Purine-2,6-diamine Derivatives as Cyclin-dependent Kinase （CDK） Inhibitors

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Chinese Journal of Chemistry 2013年第9期31卷 1181-1191页

作者： Junhua Wang Quande Wang Liangren Zhang Hao Fang Department of Medicinal Chemistry School of Pharmaceutical Sciences Shandong University Jinan Shandong 250012 China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China

Novel purine-2,6-diamine derivatives were designed and synthesized as cyclin-dependent kinase （CDK） inhibi- tors. According to the preliminary biological evaluation, most of the compounds show good inhibitory activities in CDK1 enzyme assay and potent antiproliferative activities in some tumor cell lines. Especially, compound lla （IC50=0.35 μmol/L for CDK1/cyclin B and IC50： effect compared with Roscovitine （IC50= 2.54 CDK2/cyclin A）. 0.023 μmol/L for CDK2/cyclin A） possessed better inhibitory μmol/L for CDK1/cyclin B and IC50=0.092 μ mol/L for

关键词： purine derivatives CDK inhibitors antitumor agents regulation of cell cycle

Erlotinib Analogue-substituted Zinc（Ⅱ） Phthalocyanines for Small Molecular Target-based Photodynamic Cancer Therapy

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Chinese Journal of Chemistry 2016年第10期34卷 983-988页

作者： Juanjuan Chen Huannian Ye Mingjun Zhang Jinyu Li Jianyong Liu Jinping Xue State Key Laboratory of Photocatalysis on Energy and Environment & Fujian Engineering Research Center of Functional Materials College of Chemistry Fuzhou University Fuzhou Fujian 350002 China

＂Smart＂ targeted photosensitizer conjugated with small molecule target-based anticancer drug which has a sim- ple chemical structure and high stability, is a new promising targeted therapeutic strategy. We herein extended this strategy and reported a novel series of zinc（II） phthalocyanine-erlotinib analogue conjugates with different periph- eral substituted positions and lengths of the linker. Having erlotinib analogue as the targeting moiety, all conjugates exhibited high specificity and potent affinity to HepG2 cancer cells and kept high photodynamic activity （ICs0 = 3.7 -- 16.7 nmol/L）. Structure-activity relationships of these conjugates were assessed by investigating their photophys- ical/photochemical properties, targeting intracellular uptake and in vitro phototoxicity. The results suggested that a-substituted conjugates showed slightly higher photodynamic activity than ,8-substituted ones. In conclusion, we have developed a series of promising anticancer agents with high tumor selectivity and anticancer activity for targeted photodynamic therapy.

关键词： antitumor agents targeted photodynamic therapy small molecular target-based drug erlotinib,phthalocyanines

Lithocarpins E-G, Potent Anti-Tumor Tenellone-Macrolides from the Deep-Sea Fungus Phomopsis lithocarpus FS508

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Chinese Journal of Chemistry 2021年第5期39卷 1104-1112页

作者： Jianlin Xu Yuchan Chen Zhaoming Liu Saini Li Yong Wang Yuhong Ren Hongxin Liu Weimin Zhang State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbiol Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyGuangdong Institute of MicrobiologyGuangdong Academy of SciencesGuangzhouGuangdong 510070China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China

Lithocarpins E-G,featuring a rare naturally-occurring highly oxygenated tenellone-macrolide skeleton,were isolated from the culture extract of a marine-derived fungus Phomopsis lithocarpus *** structures were fully elucidated by NMR and MS spectroscopic analyses and electronic circular dichroism *** 1-3 were evaluated for their in vitro cytotoxicities against HepG2,MCF-7,SF-268,as well as A549 cell lines,among which,compound 1 exhibited inhibitory activity against HepG2 cells with an IC_(50) value of 6.3 μmol/*** further mechanistic investigation demonstrated that lithocarpin E could cause the apoptosis of HepG2 cells through activation of p-ERK,Bax,and caspase-3 gene expressions.

关键词： Phomopsis lithocarpus FS508 Polyketides Structure elucidation antitumor agents Apoptosis