abstract：PURPOSE:Among all genetic mutations of LRRK2, the G2019S mutation is the most commonly associated with the late-onset of Parkinson's disease (PD). Hence, one potential therapeutic approach is to block the hyperactivity of mutated LRRK2 induced by kinase inhibition. To date, only a few LRRK2 kinase inhibitors have been ...

journal_title：European journal of medicinal chemistry

authors： Malik N,Kornelsen R,McCormick S,Colpo N,Merkens H,Bendre S,Benard F,Sossi V,Schirrmacher R,Schaffer P

更新日期：2021-02-05 00:00:00

abstract：:Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization o...

journal_title：European journal of medicinal chemistry

authors： Alves Avelar LA,Schrenk C,Sönnichsen M,Hamacher A,Hansen FK,Schliehe-Diecks J,Borkhardt A,Bhatia S,Kassack MU,Kurz T

更新日期：2021-02-05 00:00:00

abstract：:Alzheimer's disease is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of "one drug, one target" has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that ca...

journal_title：European journal of medicinal chemistry

authors： Mezeiova E,Janockova J,Andrys R,Soukup O,Kobrlova T,Muckova L,Pejchal J,Simunkova M,Handl J,Micankova P,Capek J,Rousar T,Hrabinova M,Nepovimova E,Marco-Contelles JL,Valko M,Korabecny J

更新日期：2021-02-05 00:00:00

abstract：:Nur77, an orphan nuclear receptor, is a member of the nuclear receptor superfamily. Nur77 plays important roles in various biological processes. Previously we reported that BI1071(DIM-C-pPhCF3+MeSO3-), an oxidized form and methanesulfonate salt of (4-CF3-Ph-C-DIM), can modulate Nur77's non-genomic apoptotic pathway th...

journal_title：European journal of medicinal chemistry

authors： Tu X,Chen X,Zhang D,Gao M,Liang J,Bao G,Zhang J,Peng S,Zhang X,Zeng Z,Su Y

更新日期：2021-02-05 00:00:00

abstract：:Indoleamine-2,3-dioxygenase 1 (IDO1) catalyses the first and rate limiting step of kynurenine pathway accounting for the major contributor of L-Tryptophan degradation. The Kynurenine metabolites are identified as essential cofactors, antagonists, neurotoxins, immunomodulators, antioxidants as well as carcinogens. The ...

journal_title：European journal of medicinal chemistry

authors： Singh R,Salunke DB

更新日期：2021-02-05 00:00:00

abstract：:Acquired resistance leads to the failure of EGFR TKIs in NSCLC treatment. A novel series of hydroxamic acid-containing 4-aminoquinazoline derivatives as irreversible ErbB/HDAC multitargeted inhibitors for NSCLC therapy had been designed and synthesized, which displayed weak anti-proliferative activity in several EGFR ...

journal_title：European journal of medicinal chemistry

authors： Zhao L,Fan T,Shi Z,Ding C,Zhang C,Yuan Z,Sun Q,Tan C,Chu B,Jiang Y

更新日期：2021-01-18 00:00:00

abstract：:Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies...

journal_title：European journal of medicinal chemistry

authors： Gonzalez G,Hodoň J,Kazakova A,D'Acunto CW,Kaňovský P,Urban M,Strnad M

更新日期：2021-01-16 00:00:00

abstract：:Invasive candidiasis, such as intra-abdominal candidiasis (IAC), is a significant cause of morbidity and mortality worldwide. IAC is still poorly understood, and its treatment represents a challenge for public health. In this study, we showed the in vitro anti-Candida activity of four alkaloid synthetic derivatives an...

journal_title：European journal of medicinal chemistry

authors： Andrade JT,Lima WG,Sousa JF,Saldanha AA,Nívea Pereira De Sá,Morais FB,Prates Silva MK,Ribeiro Viana GH,Johann S,Soares AC,Araújo LA,Antunes Fernandes SO,Cardoso VN,Siqueira Ferreira JM

更新日期：2021-01-15 00:00:00

abstract：:Cancer has been the second heath killer being next only to cardiovascular diseases in human society. Although many efforts have been taken for cancer therapy and many achievements have been yielded in the diagnosis and treatment of cancer, the current first-line anti-cancer agents are insufficient owing to the emergen...

journal_title：European journal of medicinal chemistry

authors： Wan Y,Long J,Gao H,Tang Z

更新日期：2021-01-15 00:00:00

abstract：:Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3...

journal_title：European journal of medicinal chemistry

authors： Liang GB,Wei JH,Jiang H,Huang RZ,Qin JT,Wang HL,Wang HS,Zhang Y

更新日期：2021-01-15 00:00:00

abstract：:The conjugation of biologically active molecules is a powerful tool for drug discovery used to target a variety of multifunctional diseases including cancer. Conjugated drugs can provide combination therapies in a single multi-functional agent and, by doing so, be more specific and powerful than conventional classic t...

journal_title：European journal of medicinal chemistry

authors： А Zolottsev V,Latysheva АS,Pokrovsky VS,Khan II,Misharin AY

更新日期：2021-01-15 00:00:00

abstract：:The marine environment with its vast biological diversity encompasses many organisms that produce bioactive natural products. Marine microorganisms are rich sources of compounds from many structural classes with a multitude of biological activities. The biosynthesis of microbial natural products depends on a variety o...

journal_title：European journal of medicinal chemistry

authors： Gozari M,Alborz M,El-Seedi HR,Jassbi AR

更新日期：2021-01-15 00:00:00

abstract：:Sorafenib is one of the clinically used anticancer agents that inhibits several kinases. In this study, novel indole-based rigid analogues of sorafenib were designed and synthesized in order to enhance kinase selectivity and hence minimize the side effects associated with its use. The target compounds possess differen...

journal_title：European journal of medicinal chemistry

authors： Sbenati RM,Zaraei SO,El-Gamal MI,Anbar HS,Tarazi H,Zoghbor MM,Mohamood NA,Khakpour MM,Zaher DM,Omar HA,Alach NN,Shehata MK,El-Gamal R

更新日期：2021-01-15 00:00:00

abstract：:Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cy...

journal_title：European journal of medicinal chemistry

authors： Orro A,Uggeri M,Rusnati M,Urbinati C,Pedemonte N,Pesce E,Moscatelli M,Padoan R,Cichero E,Fossa P,D'Ursi P

更新日期：2021-01-13 00:00:00

abstract：:The unforeseen emergence of coronavirus disease 2019 (COVID-19), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Wuhan province of China in December 2019, subsequently its abrupt spread across the world has severely affected human life. In a short span of time, COVID-19 has sacked more than one m...

journal_title：European journal of medicinal chemistry

authors： Shagufta,Ahmad I

更新日期：2021-01-12 00:00:00

abstract：:In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibit...

journal_title：European journal of medicinal chemistry

authors： Chu Z,Xu Q,Zhu Q,Ma X,Mo J,Lin G,Zhao Y,Gu Y,Bian L,Shao L,Guo J,Ye W,Li J,He G,Xu Y

更新日期：2021-01-12 00:00:00

abstract：:Tumor immunotherapy has made great progress in recent years. In the tumor microenvironment, the binding of PD-1 and its ligand PD-L1 can promote tumor immune escape and tumor survival. Clinical studies have indicated that antibodies blocking PD-1 and PD-L1 have reliable effects on many advanced malignant tumors. Howev...

journal_title：European journal of medicinal chemistry

authors： Pan C,Yang H,Lu Y,Hu S,Wu Y,He Q,Dong X

更新日期：2021-01-09 00:00:00

abstract：:Employing two different alkyne-modified dopamine agonists to construct bivalent compounds via click chemistry resulted in the identification of a bivalent ligand (11c) for dopamine D2 receptor homodimer, which, compared to its parent monomeric alkyne, showed a 16-fold higher binding affinity for the dopamine D2 recept...

journal_title：European journal of medicinal chemistry

authors： Qian M,Ricarte A,Wouters E,Dalton JAR,Risseeuw MDP,Giraldo J,Van Calenbergh S

更新日期：2021-01-04 00:00:00

abstract：:To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound ...

journal_title：European journal of medicinal chemistry

authors： Huang G,Solano CM,Melendez J,Yu-Alfonzo S,Boonhok R,Min H,Miao J,Chakrabarti D,Yuan Y

更新日期：2021-01-01 00:00:00

abstract：:Covalent drugs play corresponding bioactivities by forming covalent bonds with the target, which possess many significant pharmacological advantages including high potency, ligand efficiency, and long-lasting effects. However, development of covalent inhibitors is a challenge due to their presumed indiscriminate react...

journal_title：European journal of medicinal chemistry

authors： Liu J,Li L,Li X,Wang X,Zhao X,Qiao Y,Xu Y,Sun Y,Qian L,Liu Z,Ji A,Lou H

更新日期：2021-01-01 00:00:00

abstract：:The current epidemic of antibiotic resistant bacterial infections has fueled the demand for novel antibiotics exhibiting both antibacterial efficacy and anti-drug resistance. This need has not been fully satisfied by the conventional "one target-one molecule" approach. Consequently, there has been rising interest in t...

journal_title：European journal of medicinal chemistry

authors： Wetzel C,Lonneman M,Wu C

更新日期：2021-01-01 00:00:00

abstract：:Alzheimer's disease (AD) is the most common form of dementia characterized by presence of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of tau protein. Currently there are close to 50 million people living with dementia and this figure is expected to increase to 75 million by 2030 pu...

journal_title：European journal of medicinal chemistry

authors： Wang L,Bharti,Kumar R,Pavlov PF,Winblad B

更新日期：2021-01-01 00:00:00

abstract：:Identification of potent anticancer agents with high selectivity and low toxicity remains on the way to human health. Pyridazine featuring advantageous physicochemical properties and antitumor potential usually is regarded as a central core in numerous anticancer derivatives. There are several approved pyridazine-base...

journal_title：European journal of medicinal chemistry

authors： He ZX,Gong YP,Zhang X,Ma LY,Zhao W

更新日期：2021-01-01 00:00:00

abstract：:Isocombretastatins are the not isomerizable 1,1-diarylethene isomers of combretastatins. Both families of antimitotics are poorly soluble and new analogs with improved water solubility are needed. The ubiquitous 3,4,5-trimethoxyphenyl ring and most of its replacements contribute to the solubility problem. 39 new compo...

journal_title：European journal of medicinal chemistry

authors： Álvarez R,Aramburu L,Gajate C,Vicente-Blázquez A,Mollinedo F,Medarde M,Peláez R

更新日期：2021-01-01 00:00:00

abstract：:Facing the continuously urgent demands for novel antimicrobial agents since the growing emergence of bacterial resistance, a series of new ultra-short lipopeptides, composed of tryptophan and arginine and fatty acids, were de novo designed and synthesized in this study. Most of the new lipopeptides exhibited preferabl...

journal_title：European journal of medicinal chemistry

authors： Zhong C,Zhang F,Zhu N,Zhu Y,Yao J,Gou S,Xie J,Ni J

更新日期：2020-12-29 00:00:00

abstract：:As our research focuses on anticancer drugs, a series of novel derivatives of flexicaulin A (FA), an ent-kaurene diterpene, condensed with an aromatic ring were synthesized, and their antiproliferative activities against four human cancer cell lines (TE-1, EC109, MCF-7, and MGC-803) were evaluated. The activities of m...

journal_title：European journal of medicinal chemistry

authors： Huo JF,Hu TX,Dong YL,Zhao JZ,Liu XJ,Li LL,Zhang XY,Li YF,Liu HM,Ke Y,Wang C

更新日期：2020-12-15 00:00:00

abstract：:Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. It is caused by different mutations in the cystic fibrosis transmembrane regulator protein (CFTR) gene, with F508del being the most common. During the last years, small-molecule therapy chosen to contrast CF relied on com...

journal_title：European journal of medicinal chemistry

authors： Parodi A,Righetti G,Pesce E,Salis A,Tasso B,Urbinati C,Tomati V,Damonte G,Rusnati M,Pedemonte N,Cichero E,Millo E

更新日期：2020-12-15 00:00:00

abstract：:UNC51-like kinase1 (ULK1) recruits its binding partners and initiates the autophagy process in cancer. ULK1 is significantly overexpressed in Non-small cell lung cancer (NSCLC) and negatively correlated with clinical prognosis in NSCLC patients. Based upon the binding features of ULK1, we explored the pharmacophore mo...

journal_title：European journal of medicinal chemistry

authors： Sun D,Yang Z,Zhen Y,Yang Y,Chen Y,Yuan Y,Zhang L,Zeng X,Chen L

更新日期：2020-12-15 00:00:00

abstract：:The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyry...

journal_title：European journal of medicinal chemistry

authors： Abdullaha M,Nuthakki VK,Bharate SB

更新日期：2020-12-01 00:00:00

abstract：:Boronic acid (and ester) prodrugs targeting the overexpressed level of reactive oxygen species within tumor microenvironment represent a promising area for the discovery of new selective anticancer chemotherapy. This strategy that emerged only ten years ago is exponentially growing and could demonstrate its clinical u...

journal_title：European journal of medicinal chemistry

authors： Maslah H,Skarbek C,Pethe S,Labruère R

更新日期：2020-12-01 00:00:00

abstract：:A series of novel pleuromutilin derivatives with substituted 6-methylpyrimidine moieties was designed, synthesized, and evaluated for their antibacterial activities. Most of the tested compounds exhibited potent antibacterial activities against Staphylococcus aureus ATCC 25923 (S. aureus-25923), methicillin-resistant ...

journal_title：European journal of medicinal chemistry

authors： Fan Y,Liu Y,Wang H,Shi T,Cheng F,Hao B,Yi Y,Shang R

更新日期：2020-12-01 00:00:00

abstract：:Emulsions have shown great potential in the delivery of various types of cargoes such as nucleic acids and proteins. In this study, fluorinated polymer emulsions (PFx@PFD-n) were prepared using fluorinated polymers with different structures as surfactant in PFD emulsions under ultrasound. These polymer emulsions gave ...

journal_title：European journal of medicinal chemistry

authors： Xiao YP,Zhang J,Liu YH,Huang Z,Yu XQ

更新日期：2020-12-01 00:00:00

abstract：:The interaction between menin and mixed lineage leukemia (MLL) was identified as an interesting target for treating some cancers including acute leukemia. On the basis of the known crystal structure of the MBM1-menin complex (MBM - menin binding motif), several cyclic peptides were designed. Elaboration of the effecti...

journal_title：European journal of medicinal chemistry

authors： Fortuna P,Linhares BM,Purohit T,Pollock J,Cierpicki T,Grembecka J,Berlicki Ł

更新日期：2020-12-01 00:00:00

abstract：:Protein-protein interactions (PPIs) play a pivotal role in extensive biological processes and are thus crucial to human health and the development of disease states. Due to their critical implications, PPIs have been spotlighted as promising drug targets of broad-spectrum therapeutic interests. However, owing to the g...

journal_title：European journal of medicinal chemistry

authors： Qiu Y,Li X,He X,Pu J,Zhang J,Lu S

更新日期：2020-12-01 00:00:00

abstract：:A series of novel vinyl selenone derivatives were designed, synthesized and evaluated as the tubulin polymerization inhibitors using a bioisosteric strategy. Among them, the representative compound 11k exhibited satisfactory anti-proliferative activities with IC50 values ranging from 0.287 to 0.621 μM against a panel ...

journal_title：European journal of medicinal chemistry

authors： Zhu H,Sun H,Liu Y,Duan Y,Liu J,Yang X,Li W,Qin S,Xu S,Zhu Z,Xu J

更新日期：2020-12-01 00:00:00

abstract：:Novel imidazoline benzimidazole derivatives containing diversely substituted phenoxy moieties were synthesized with the aim of evaluating their antitrypanosomal activity, DNA/RNA binding affinity and in vitro ADME properties. The presence of the diethylaminoethyl subunit in 18a-18c led to enhanced antitrypanosomal pot...

journal_title：European journal of medicinal chemistry

authors： Popov AB,Krstulović L,Koštrun S,Jelić D,Bokulić A,Stojković MR,Zonjić I,Taylor MC,Kelly JM,Bajić M,Raić-Malić S

更新日期：2020-12-01 00:00:00

abstract：:Acetyl-CoA carboxylase (ACC) is a rate-limiting enzyme in de novo fatty acid synthesis, which plays a critical role in the growth and survival of cancer cells. In this study, a series of spiroketopyrazole derivatives bearing quinoline moieties were synthesized, and in vitro anticancer activities of these compounds as ...

journal_title：European journal of medicinal chemistry

authors： Huang T,Wu X,Yan S,Liu T,Yin X

更新日期：2020-11-27 00:00:00

abstract：:A series of 4-pyridylpiperazine derivatives with varying regulatory region substituents proved to be potent histamine H3 receptor (H3R) ligands in the nanomolar concentration range. The most influential modification that affected the affinity toward the H3R appeared by introducing electron-withdrawing moieties into th...

journal_title：European journal of medicinal chemistry

authors： Szczepańska K,Pockes S,Podlewska S,Höring C,Mika K,Latacz G,Bednarski M,Siwek A,Karcz T,Nagl M,Bresinsky M,Mönnich D,Seibel U,Kuder KJ,Kotańska M,Stark H,Elz S,Kieć-Kononowicz K

更新日期：2020-11-24 00:00:00

abstract：:It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine com...

journal_title：European journal of medicinal chemistry

authors： Zhang G,Wang M,Zhao J,Wang Y,Zhu M,Wang J,Cen S,Wang Y

更新日期：2020-11-15 00:00:00

abstract：:In this study, a series of 1,3,4-oxadiazole derivatives (5a-s, 10a-s, and 16a-d) were designed and synthesized using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models, to test the anticonvulsant activity of the target compounds in vivo. The neurotoxicity (NT) of the target compounds was mea...

journal_title：European journal of medicinal chemistry

authors： Wang S,Liu H,Wang X,Lei K,Li G,Li J,Liu R,Quan Z

更新日期：2020-11-15 00:00:00