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A dual-protease-triggered chemiluminescent probe for precise tumor imaging

Chinese Chemical Letters 2025年第2期36卷 302-306页

作者： Zhihui Zhang Ru Sun Chong Bian Hongbo Wang Zhen Zhao Panpan Lv Jianzhong Lu Haixin Zhang Hulie Zeng Yuanyuan Chen Zhijuan Cao department of pharmaceutical Analysis School of PharmacyFudan University Minhang Branch Zhongshan HospitalFudan University China State Institute of pharmaceutical Industry Shanghai Jahwa United Co. Ltd.

Imaging detection of interlinked dual proteases is imperative for precise tumor imaging, which remains challenging due to limited modification position of specific substrate and possible steric ***, we have developed a unimolecular chemiluminescent probe(LGP-CL) tandemly activated by two proteases interlinked with liver cancer to achieve precise tumor imaging. Probe LGP-CL consists of a phenoxy-dioxetane scaffold caged by a tripeptide substrate(LGP, leucine-glycine-proline) as the sensing layer, which can be cleaved sequentially by aminopeptidase N(APN) and dipeptidyl peptidase IV(DPPIV)to turn on a strong chemiluminescent signal, and silenced by specific inhibitor of each enzyme, which accounts for an integrated logic gate(AND, OR and INHIBIT). The successful cleavage of dual proteases on the metabolic site depends on the proper structure of the tripeptide substrate, as confirmed by two probes design. Probe LGP-CL(LGP as the substrate) enables the excellent “dual-lock-dual-key” fit with a382-fold enhancement of chemiluminescent emission while no obvious signal is observed by using GPLCL(GPL as the substrate). By virtue of its rapid response(several minutes), high sensitivity and good cell viability, probe LGP-CL has been utilized to evaluate upregulated levels of proteases in vitro and in living systems, especially to distinguish liver tumor cells(Hep G2) from others(LO2, MCF-7, MCF-10a and RAW264.7). Overall, the newly developed CL probe may facilitate rapid investigation into the role played by proteases in liver diseases, enabling timely selection appropriate treatment. Therefore, our work not only sheds light on the rational design of optical probes for dual protease imaging, but provides a promising tool for clinical diagnosis and even drug discovery.

关键词： Chemiluminescent Dual-protease imaging Logic gates Phenoxy-dioxetane scaffold Tripeptide substrate

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Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta department of pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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Understanding Investigational Perspective of Antioxidant and Antibacterial Properties of Rice

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Rice science 2025年第1期32卷 15-31页

作者： Intan FARAHANAH Shariza SAHUDIN Hannis Fadzillah MOHSIN Siti Alwani ARIFFIN Liyana Dhamirah AMINUDDIN department of pharmaceutical technology Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia department of Chemistry Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia department of Pharmacology and Life Sciences Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia Faculty of Medicine Universiti Teknologi MaraSungai Buloh CampusSelangor 42300Malaysia

Whole-grain rice has gained significant attention for its potential health benefits,particularly because of its antioxidant and antibacterial *** this growing interest,there remains a pressing need for a comprehensive evaluation of the methods used to analyze these bioactive compounds,considering the diversity of rice types and the influence of environmental *** review aims to provide an in-depth overview of recent analytical methods,particularly those employed over the last five years,to assess the antioxidant and antibacterial properties of *** focuses on commonly used antioxidant assays,such as the 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity assay,which encompasses both single electron transfer and hydrogen atom transfer *** antioxidant assays are also discussed,alongside methods used to evaluate antibacterial properties,including disc diffusion,well diffusion,broth or agar dilution,and advanced techniques such as flow cytofluorometric and bioluminescent *** review further explores the bacterial strains most frequently studied,including Bacillus cereus,Listeria monocytogenes,Escherichia coli,and Salmonella *** highlights the key techniques and parameters employed to ascertain and quantify the antioxidant and antibacterial potential of rice,while critically analysing the strengths and limitations of these *** synthesizing current methods and offering insights into their application,this review can be served as a guide for future research aimed at standardizing and improving the assessment of rice’s bioactive properties,paving the way for broader scientific and practical applications.

关键词： pigmented rice antioxidant activity antibacterial activity

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Approved delivery strategies for biopharmaceuticals

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Chinese Chemical Letters 2025年第2期36卷 69-79页

作者： Makhloufi Zoulikha Zhongjian Chen Jun Wu Wei He School of pharmacy China Pharmaceutical University Shanghai Skin Disease Hospital Tongji University School of Medicine department of Geriatric Cardiology Jiangsu Provincial Key Laboratory of Geriatrics The First Affiliated Hospital of Nanjing Medical University

In recent years, biopharmaceuticals have witnessed remarkable advancements, transforming the landscape of therapeutic interventions. Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes. However, their clinical success hinges significantly on overcoming drug delivery challenges related to stability, intracellular delivery, immunogenicity, and pharmacokinetic properties. Herein, we provide an overview of various marketed macromolecules, including nucleic acids, and immunotherapeutic agents such as cytokines and monoclonal antibodies, as well as other therapeutic peptides/proteins like enzymes, hormones, and coagulation factors. Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products, offering valuable insights for both scientific research and the pharmaceutical industry.

关键词： Biopharmaceuticals Drug delivery Monoclonal antibodies Nucleic acids Proteins

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Cerbera odollam fruit extracts enhance anti-cancer activity of sorafenib in HCT116 and HepG2 cells

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Chinese Herbal Medicines 2025年第1期17卷 108-126页

作者： Supawadee Parhira Orakot Simanurak Khemmachat Pansooksan Julintorn Somran Apirath Wangteeraprasert Zhihong Jiang Liping Bai Pranee Nangngam Dumrongsak Pekthong Piyarat Srisawang department of pharmaceutical technology Faculty of Pharmaceutical Sciences Naresuan University Center of Excellence for Innovation in Chemistry Naresuan University Center of Excellence for Environmental Health and Toxicology Faculty of Pharmaceutical Sciences Naresuan University department of Physiology Faculty of Medical Science Naresuan University department of pharmaceutical Chemistry and Pharmacognosy Faculty of Pharmaceutical Sciences Naresuan University department of Pathology Faculty of Medicine Naresuan University department of Medicine Faculty of Medicine Naresuan University State Key Laboratory of Quality Research in Chinese Medicine Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease Macau Institute for Applied Research in Medicine and Health Macau University of Science and Technology department of Biology Faculty of Science Naresuan University department of pharmacy Practice Faculty of Pharmaceutical Sciences Naresuan University Center of Excellence in Medical Biotechnology Faculty of Medical Science Naresuan University

Objective:While higher therapeutic doses of toxic cardiac glycosides derived from Cerbera odollam are frequently employed in cases of suicide or homicide,ongoing research is investigating the potential anticancer properties of low-concentration extracts obtained from the fruits of *** present study aimed to determine the enhanced anticancer effects and minimize potential side effects of combining extracts from *** fruits from Thailand with sorafenib against HCT116 and HepG2 ***:The dried powder of fresh green fruits of *** was fractionated,and its phytochemical contents,including total cardiac glycosides,phenolics,flavonoids,and triterpenoids,were *** cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT *** fractions showing the most significant response in HCT116 and HepG2 cells were subsequently combined with sorafenib to examine their synergistic *** induction,cell cycle progression,and mitochondrial membrane potential（MMP） were then *** underlying mechanism of the apoptotic effect was further investigated by analyzing reactive oxygen species（ROS） generation and the expression levels of antioxidant ***:Phytochemical analysis showed that ***-ethyl acetate fraction（COEtOAc） was rich in cardiac glycosides,phenolics,and flavonoids,while the dichloromethane fraction（CODCM） contained high levels of triterpenoids and *** 24 h treatment,HCT116 showed the most significant response to COEtOAc,while HepG2 responded well to CODCM with IC50values of（42.04±16.94） μg/mL and（123.75±14.21） μg/m L,***,COEtOAc（20 μg/mL） or CODCM（30 μg/mL）,both administered at sub-IC50concentrations,were combined with sorafenib at 6 μmol/L for HCT116 cells and2 μmol/L for HepG2 cells,incubated for 24 *** combination resulted in a significant suppression in cell viability by approximately 50%.The combination of treatments marked

关键词： apoptosis Cerbera odollam Gaertn. HCT116 HepG2 reactive oxygen species sorafenib

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Efficient continuous synthesis of 2-[3-(trifluoromethyl)phenyl]malonic acid,a key intermediate of Triflumezopyrim,coupling with esterification-condensation-hydrolysis

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Chinese Chemical Letters 2025年第1期36卷 234-238页

作者： Yuexiang Liu Xiangqiao Yang Tong Lin Guantian Yang Xiaoyong Xu Bubing Zeng Zhong Li Weiping Zhu Xuhong Qian Shanghai Key Laboratory of Chemical Biology School of PharmacyEast China University of Science and TechnologyShanghai 200237China Shanghai Frontiers Science Center of Optogenetic Techniques for Cexll Metabolism School of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Engineering Research Center of pharmaceutical Process Chemistry Ministry of EducationSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Shanghai Key Laboratory of Green Chemistry and Chemical Processes Department of ChemistrySchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

Triflumezopyrim(TFM)is a novel mesoionic pyrido[1,2-α]pyrimidinones insecticide,which acts on nicotinic acetylcholine receptors(n ACh Rs)and has no cross-resistance with other ***,we firstly developed a new continuous flow approach to synthesis 2-[3-(trifluoromethyl)phenyl]malonic acid,a key intermate of TFM,coupling with esterification,condensation,and *** three-step reactions were optimized and transformed into a continuous synthesis mode by three micro reaction *** with the batch mode,the total reaction time and overall separation yield were improved from more than 12 h and 60%to 18 min and 73.38%,*** solvent consumption and waste emission were significantly reduced,which also provides an eco-friendly and efficient potential tool for the development and production of mesoionic pyrido[1,2-α]pyrimidinones insecticide.

关键词： Triflumezopyrim(TFM) 2-[3-(Trifluoromethyl)phenyl]malonic acid Continuous flow synthesis Micro-reactor

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Ferulic acid alleviates long-term avermectin-induced damage to the spleen of carp and restores its inflammatory response and oxidative balance

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Journal of Environmental Sciences 2025年第5期151卷 616-626页

作者： Hanyu Wang Shenye Feng Enzhuang Pan Xiaomeng Ji Mengyuan Zhou Shuai Zhang Baoshi Xu Huimiao Feng Jilei Yin Zibo Dong Jiangsu Key Laboratory of Marine Bioresources and Environment Co-Innovation Center of Jiangsu Marine Bio-industry TechnologyJiangsu Marine Pharmaceutical Resources Development Engineering Research CenterJiangsu Key Laboratory of Marine Pharmaceutical Compound ScreeningCollege of PharmacyJiangsu Ocean UniversityLianyungang 222005China department of Traditional Chinese Medicine Jiangsu Union Technical Institute Lianyungang Branch institute of Traditional Chinese MedicineLianyungang 222006China

Extensive use of avermectin(AVM)in agriculture can seriously contaminate fish in *** acid(FA)is a strong antioxidant sourced from plants and is widely applied in food and medicine,but its protective function on the immunological damage caused by AVM is still *** this study,carp were chronically exposed to(1/1096 hr LC_(50))AVM for 30 day(s),with a dietary supplement of FA(400 mg/kg)to assess its effects on carp *** experimental groups(n=10)included:control,AVM-exposed(2.404μg/L),FA+AVM co-treated,and FA ***-term AVM exposure altered spleen tissue,reducing serum complement C3(p<0.01)and immunoglobulin M levels(p<0.001),and increasing proinflammatory tnf-α(p<0.001),il-6(p<0.001),il-1β(p<0.001),and inos mRNA levels,whilst down-regulating the anti-inflammatory tgf-β(p<0.05).Additionally,it disrupted the balance of oxidative stress indicators such asMDA(p<0.001),T-AOC,GSH,and CAT,leading to spleen tissue apoptosis(42.4%).However,the addition of FA reversed these conditions,elevated the anti-inflammatory factor,and improved spleen immune function following chronic exposure to AVMin ***,the ability to restore oxidative homeostasis in carp by adjusting the Nrf2/NQO-1 axis protected the health of spleen *** discovery also supports the development of fish feed for aquaculture.

关键词： Avermectin Ferulic acid Oxidative stress Inflammation response

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Oscillatory flow reactor facilitates fast photochemical Wolff rearrangement toward synthesis of α-substituted amides in flow

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Chinese Chemical Letters 2025年第2期36卷 389-393页

作者： Huashan Huang Jingze Chen Luyun Zhang Hong Yan Siqi Li Fen-Er Chen Institute of pharmaceutical Science and technology College of Chemistry Fuzhou University Key Laboratory of Natural Medicines of the Changbai Mountain Ministry of Education Molecular Medicine Research Center College of Pharmacy Yanbian University Engineering Center of Catalysis and Synthesis for Chiral Molecules Department of Chemistry Fudan University Shanghai Engineering Center of Industrial Catalysis for Chiral Drugs

A visible light-promoted fast photochemical Wolff rearrangement was developed toward synthesis of α-substituted amides in continuous flow with the use of a photochemical oscillatory flow reactor(POFR).The control experiment indicates that a fast process of the Wolff rearrangement(<40 s) is involved. Notably, this protocol does not require excess use of any reactants, and the resulting α-substituted amides could be isolated by recrystallization in good to excellent yields.

关键词： Flow photochemistry Ketene Oscillatory flow reactor Wolff rearrangement α-Substituted amides

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Small modifications of endo-functionalized cavities lead to large changes in molecular interaction in water

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Science China Chemistry 2025年第1期68卷 369-376页

作者： Song-Meng Wang Hao Nian Yan-Fang Wang Li-Shuo Zheng Yu-Tao Zheng Yi-Wei Dong Liping Huang Xiaoping Wang Wei Jiang Liu-Pan Yang department of Chemistry Southern University of Science and TechnologyShenzhen 518055China School of pharmaceutical Science Hengyang Medical SchoolUniversity of South ChinaHengyang 421001China School of Chemistry and pharmaceutical Sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesGuangxi Normal UniversityGuilin 541004China

Studying molecular recognition in aqueous environments is crucial for understanding biological ***,we present a series of N-doped endo-functionalized anthracene-based cavities by introducing inward-directed pyridine *** subtle modifications can significantly affect the binding properties of these receptors,which is similar to the mutations in biological *** theoretical calculations and molecular recognition experiments demonstrated that these“mutations”have an impact on the hydrophobicity and charge distribution of the hosts,consequently significantly influencing molecular *** is crucial for understanding the intricate mechanisms of molecular-level interactions in biological receptors.

关键词： host-guest interaction hydrophobic effect endo-functionalized cavity mutation pyridine

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Rosa moschata ameliorates haloperidol-induced Parkinson's disease via reduction of neurodegeneration and oxidative stress

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Asian Pacific Journal of Tropical Biomedicine 2025年第1期15卷 24-33,I0013-I0015页

作者： Badriyah S.Alotaibi Uzma Saleem Maryam Farrukh Zunera Chaudhary Nabia Anwar Ifat Alsharif Abdullah R.Alanzi Tasahil S.Albishi Fatima A.Jaber Wedad Saeed Al-Qahtani Muhammad Ajmal Shah department of pharmaceutical Sciences College of PharmacyPrincess Nourah bint Abdulrahman UniversityP.O.Box 84428Riyadh 11671Saudi Arabia Punjab University College of pharmacy University of the PunjabLahore-54000Pakistan department of Pharmacology Faculty of Pharmaceutical SciencesGovt.College UniversityFaisalabad-38000Pakistan department of Biology Jamoum University CollegeUmm Al-Qura University-21955 MakkahSaudi Arabia department of Pharmacognosy College of PharmacyKing Saud UniversityRiyadh-11451Saudi Arabia department of Biology College of SciencesUmm Al-Qura UniversityMakkahSaudi Arabia department of Biological Sciences College of ScienceUniversity of JeddahJeddah 21589Saudi Arabia department of Forensic Sciences College of Criminal JusticeNaif Arab University for Security SciencesP.O.Box 6830Riyadh 11452Saudi Arabia department of pharmacy Hazara UniversityMansehra-21300Pakistan

Objective:To investigate the effect of Rosa moschata(***)extract on haloperidol-induced Parkinson’s disease(PD)in ***:Haloperidol(1 mg/kg)was given to rats intraperitoneally for 3 weeks for induction of *** extract(150,300 and 600 mg/kg)was administered orally for 21 *** neuroprotective role of *** leaf extract in PD was explored by performing neurobehavioral tests and RT-PCR analysis and measuring neurotransmitters and oxidative stress ***:An improvement in motor functions and muscle strength was observed in PD rats treated with *** *** levels of dopamine,serotonin,noradrenaline,superoxide dismutase,catalase,glutathione,and superoxide dismutase were significantly increased(P<0.001),whereas acetylcholinesterase and malondialdehyde levels were markedly decreased by treatment with *** extract(P<0.001).The extract also markedly downregulated the mRNA expressions of IL-1β,α-synuclein,IL-1α,and TNF-αin brain ***,histopathological analysis indicated that neurofibrillary tangles and plaques were noticeably decreased in a dose-dependent manner in PD rats treated with *** ***:*** extract alleviates haloperidol-induced PD in rats by reducing oxidative stress and *** may be used for management and treatment of *** additional studies are required to confirm its efficacy and molecular mechanisms.

关键词： Parkinson’s disease Rosa moschata Neurotransmitter,α-Synuclein Haloperidol Neurodegeneration

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