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Benzimidazole and its derivatives as cancer therapeutics:The potential role from traditional to precision medicine

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Acta Pharmaceutica Sinica B 2023年第2期13卷 478-497页

作者： Yeuan Ting lee Yi Jer Tan Chern Ein oon Institute for Research in Molecular Medicine(INFORMM) Universiti Sains Malaysia11800 MindenPenangMalaysia

Cancer is the second leading cause of mortality globally which remains a continuing threat to human health *** insensitivity and resistance are critical hurdles in cancer treatment;therefore,the development of new entities targeting malignant cells is considered a high *** therapy is the cornerstone of precision *** synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological *** has a heterocyclic pharmacophore,which is an essential scaffold in drug and pharmaceutical *** studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics,either through targeting specific molecules or non-gene-specific *** review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure-activity relationship from conventional anticancer to precision healthcare and from bench to clinics.

关键词： Benzimidazole derivatives Targeted therapy Anticancer Precision medicine

Formation of intermetallic compound at interface between rare earth elements and ferritic-martensitic steel by fuel cladding chemical interaction

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Journal of Rare Earths 2012年第6期30卷 599-603页

作者： Jun Hwan Kim Byoung oon lee Chan Bock lee Seung Hyun Jee Young Soo Yoon Advanced Fuel Development Division Korea Atomic Energy Research InstituteP.O.Box 105YuseongDaejeon305-600Republic of Korea Department of Mate-rials Science and Engineering Yonsei University134 Sinchon DongSeoul120-749Republic of Korea

The intermetallic compounds formation at interface between rare earth elements and clad material were investigated to demonstrate the effects of rare earth elements on fuel-cladding chemical interaction （FCCI） behavior. Mischmetal （70Ce-30La） and Nd were prepared as rare earth elements. Diffusion couple testing was performed on the rare earth elements and cladding （9Cr2W steel） near the operation temperature of （sodium-cooled fast reactor） SFR fuel. The performance of a diffusion barrier consisting of Zr and V metallic foil against the rare earth elements was also evaluated. Our results showed that Ce and Nd in the rare earth elements and Fe in the clad material interdiffused and reacted to form intermetallic species according to the parabolic rate law, describing the migration of the rare earth element. The diffusion of Fe limited the reaction progress such that the entire process was governed by the cubic rate law. Rare earth materials could be used as a surrogate for high burnup metallic fuels, and the performance of the barrier material was demonstrated to be effective.

关键词： intermetallic compound sodium-cooled fast reactor (SFR) metallic fuel fuel-cladding chemical interaction (FCCI) rare earths Barrier

BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis

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World Journal of Gastrointestinal Oncology 2023年第5期15卷 810-827页

作者： Chern Ein oon Ayappa V Subramaniam Lik Yang Ooi Ashwaq Hamid Salem Yehya Yeuan Ting lee Gurjeet Kaur Sreenivasan Sasidharan Beiying Qiu Xiaomeng Wang Institute for Research in Molecular Medicine Universiti Sains MalaysiaPenang 11800Malaysia Cancer Research Eman BiodiscoveriesKedah 08000Malaysia Vatche and Tamar Division of Digestive Diseases Department of MedicineDavid Geffen School of Medicine at University of California Los AngelesLos AngelesCA 90095United States Academic Clinical Program Duke-NUS Medical SchoolNational University of SingaporeSingapore 169857Singapore Singapore National Eye Centre Singapore Eye Research InstituteSingapore 168751Singapore

BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor *** dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)***(SIRT)enzymes are highly expressed in blood ***9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in ***,its role has yet to be explored in CRC tumor *** To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo *** ***926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein ***,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in *** effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis *** co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on *** effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse ***116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,*** BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 *** compound also arrested the cells at G1 phase and i

关键词： Colorectal cancer BZD9L1 Sirtuin Benzimidazole Angiogenesis

Selective conversion of N_(2) to NH_(3) on highly dispersed RuO_(2) using amphiphilic ionic liquid-anchored fibrous carbon structure

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Journal of Energy Chemistry 2022年第4期31卷 474-482页

作者： Kahyun Ham Muhammad Salman Sunki Chung Minjun Choi HyungKuk Ju Hye Jin lee Jaeyoung lee School of Earth Sciences and Environmental Engineering Gwangju Institute of Science and Technology(GIST)123 Cheomdangwagi-RoGwangju 61005South Korea International Future Research Center of Chemical Energy Storage and Conversion Processes GIST123 Cheomdangwagi-RoGwangju 61005South Korea Ertl Center for Electrochemical and Catalysis GIST123 Cheomdangwagi-RoGwangju 61005South Korea Department of Chemistry and Green-Nano Materials Research Center Kyungpook National University80 Daehak-RoDaegu-city 41566South Korea Hydrogen Research Department Korea Institute of Energy Research152 Gajeong-RoYuseong-guDaejeon 34129South Korea

Ammonia (NH_(3)) plays a key role in the agricultural fertilizer and commodity chemical industries and is useful for exploring hydrogen storage *** electrochemical nitrogen reduction reaction (NRR) is receiving attention as an environmentally sustainable NH_(3) synthesis replacement for the traditional Haber–Bosch process owing to its near ambient reaction conditions (<100℃ and 1 atm).However,its NH_(3) yield and faradaic efficiency are extremely low because of the sluggish kinetics of N≡N bond dissociation and the hindrance from competitive hydrogen *** overcome these challenges,we herein introduce a dual-functionalized ionic liquid (1-(4-hydroxybutyl)-3-methylimidazolium hydroxide[HOBIM]OH) for a highly dispersed ruthenium oxide electrocatalyst to achieve a biased *** observed uniform distribution of RuO_(2) on the carbon fiber and increase in the surface area for N_(2) adsorption by limiting proton access can be attributed to the presence of imidazolium ***,extensive N_(2) adsorption contributes to enhanced NRR selectivity with an NH_(3) yield of 3.0×10^(-10)mol cm^(-2)s^(-1)(91.8μg h^(-1)mg^(-1)) and a faradaic efficiency of 2.2%at-0.20 V_(RHE).We expect our observations to provide new insights into the design of effective electrode structures for electrochemical NH;synthesis.

关键词： Ammonia synthesis Nitrogen reduction reaction Imidazolium-based ionic liquid Ruthenium oxide