abstract：:P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF V60...

journal_title：Bioorganic & medicinal chemistry

authors： Ali EMH,Abdel-Maksoud MS,Hassan RM,Mersal KI,Ammar UM,Se-In C,He-Soo H,Kim HK,Lee A,Lee KT,Oh CH

更新日期：2021-02-01 00:00:00

abstract：:Accumulation and deposition of misfolded amyloid β (Aβ) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aβ peptide. We have developed synthetic breaker pep...

journal_title：Bioorganic & medicinal chemistry

authors： Ghosh N,Kundu LM

更新日期：2021-01-16 00:00:00

abstract：:Small interfering RNA (siRNA) exhibits gene-specific RNAi activity by the formation of RISC complex with mRNA of gene. The structural modification of siRNA at appropriate positions affects the structure of RISC complex and then RNAi activity. The modified siRNA are mostly prepared from the incorporation of sugar ring ...

journal_title：Bioorganic & medicinal chemistry

authors： Bollu A,Hassan MK,Dixit M,Sharma NK

更新日期：2021-01-15 00:00:00

abstract：:A new efficient approach to the synthesis of 6-alkenyl substituted pyridoxine derivatives has been developed. A series of 31 novel alkenyl pyridoxine derivatives, stilbene-based bioisosteric analogs of estradiol, were synthesized. In vitro cytotoxicity of the obtained compounds against MCF-7 (ER+) breast cancer tumor ...

journal_title：Bioorganic & medicinal chemistry

authors： Pugachev MV,Pavelyev RS,Nguyen TNT,Gabbasova RR,Bulatov TM,Iksanova AG,Aljondi B,Bondar OV,Grishaev DY,Yamaleeva ZR,Kataeva ON,Nikishova TV,Balakin KV,Shtyrlin YG

更新日期：2021-01-15 00:00:00

abstract：:Nicotinamide adenine dinucleotide phosphate (NADP) is an indispensable metabolic co-substrate and nicotinic acid adenine dinucleotide phosphate (NAADP) is an important Ca2+ releasing intracellular second messenger. Exploration of the NADP and NAADP interactome often requires the synthesis of NADP derivatives substitut...

journal_title：Bioorganic & medicinal chemistry

authors： Su P,Bretz JD,Gunaratne GS,Marchant JS,Walseth TF,Slama JT

更新日期：2021-01-15 00:00:00

abstract：:The application of intensity-based H2O2-responsive fluorescence nanoprobe for circulating tumor cell detection was limited by the complex background and the nanoprobe uptake in each CTC. In this context, we developed a ratiometric fluorescence nanoprobe, on which a H2O2-responsive subunit and a stable subunit grafted ...

journal_title：Bioorganic & medicinal chemistry

authors： Pan R,Lu X,Ju J,Guan Q,Su Y,Li C,Li P

更新日期：2021-01-15 00:00:00

abstract：:Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has a single chiral carbon in its structure and exists naturally as a racemic mixture. Our previous study showed (S)-erypoegin K selectively exhibits potent anti-proliferative and apoptosis-inducing activity against human leukemia HL-60 c...

journal_title：Bioorganic & medicinal chemistry

authors： Hikita K,Yamakage Y,Okunaga H,Motoyama Y,Matsuyama H,Matsuoka K,Murata T,Nakayoshi T,Oda A,Kato K,Tanaka H,Asao N,Dan S,Kaneda N

更新日期：2021-01-15 00:00:00

abstract：:In analogy to antiviral acyclic nucleoside phosphonates, a series of 5-amino-3-oxo-1,2,4-thiadiazol-3(2H)-ones bearing a 2-phosphonomethoxyethyl (PME) or 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) group at the position 2 of the heterocyclic moiety has been synthesized. Diisopropyl esters of PME- and HPMP-amines have ...

journal_title：Bioorganic & medicinal chemistry

authors： Pomeislová A,Otmar M,Rubešová P,Benýšek J,Matoušová M,Mertlíková-Kaiserová H,Pohl R,Poštová Slavětínská L,Pomeisl K,Krečmerová M

更新日期：2021-01-06 00:00:00

abstract：OBJECTIVE:A new family of 3'-(Mono, di or tri-substituted phenyl)-4'-(4-(methylsulfonyl) phenyl) spiroisoxazoline derivatives containing indanone spirobridge was designed, synthesized, and evaluated for their selective COX-2 inhibitory potency and cytotoxicity on different cell lines. METHODS:A synthetic reaction base...

journal_title：Bioorganic & medicinal chemistry

authors： Abolhasani H,Zarghi A,Komeili Movahhed T,Abolhasani A,Daraei B,Dastmalchi S

更新日期：2021-01-02 00:00:00

abstract：:Recent years have seen a resurgence in drug discovery efforts aimed at the identification of covalent inhibitors which has led to an explosion of literature reports in this area and most importantly new approved therapies. These reports and breakthroughs highlight the significant investments made across the industry i...

journal_title：Bioorganic & medicinal chemistry

authors： Thorarensen A,Balbo P,Banker ME,Czerwinski RM,Kuhn M,Maurer TS,Telliez JB,Vincent F,Wittwer AJ

更新日期：2021-01-01 00:00:00

abstract：:Despite the serious public health problems caused by Chagas disease in several countries, the available therapy remains with only two drugs that are poorly active during the chronic phase of the disease in addition to having severe side effects. In search of new trypanocidal agents, herein we describe the synthesis an...

journal_title：Bioorganic & medicinal chemistry

authors： Ribeiro JLS,Soares JCAV,Portapilla GB,Providello MV,Lima CHS,Muri EMF,de Albuquerque S,Dias LRS

更新日期：2021-01-01 00:00:00

abstract：:A series of non-covalent piperidine-containing peptidyl derivatives with various substituents at side chains of different residues were designed, synthesized and evaluated as proteasome inhibitors. After proteasome inhibitory evaluations of all the synthesized target compounds, selected ones were tested for their anti...

journal_title：Bioorganic & medicinal chemistry

authors： Zhao Y,Xu L,Zhang J,Zhang M,Lu J,He R,Xi J,Zhuang R,Li J,Zhou Y

更新日期：2021-01-01 00:00:00

abstract：:The human skin is constantly exposed to external factors that affect its integrity, UV radiation being one of the main stress factors. The repeated exposure to this radiation leads to increased production of Reactive Oxygen Species (ROS) which activate a series of processes involved in photoaging. Excessive UV exposur...

journal_title：Bioorganic & medicinal chemistry

authors： Rosa GP,Palmeira A,Resende DISP,Almeida IF,Kane-Pagès A,Barreto MC,Sousa E,Pinto MMM

更新日期：2021-01-01 00:00:00

abstract：:This review discusses all pyridine alkaloids with CNS activity, their therapeutic potential, and the interesting array of sources whence they originate. ...

journal_title：Bioorganic & medicinal chemistry

authors： Lin SX,Curtis MA,Sperry J

更新日期：2020-12-15 00:00:00

abstract：:The chemical cross-linking of complexes of proteins with nucleic acids is often used in structural and mechanistic studies of these oftentimes unstable and transient complexes. To date, no method has been reported for the thiol-based conjugation of proteins with an RNA backbone, mainly because of instability of the mo...

journal_title：Bioorganic & medicinal chemistry

authors： Hyjek-Składanowska M,Stasińska AR,Napiórkowska-Gromadzka A,Bartłomiejczak A,Seth PP,Chmielewski MK,Nowotny M

更新日期：2020-12-01 00:00:00

abstract：:In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsoma...

journal_title：Bioorganic & medicinal chemistry

authors： Degorce SL,Aagaard A,Anjum R,Cumming IA,Diène CR,Fallan C,Johnson T,Leuchowius KJ,Orton AL,Pearson S,Robb GR,Rosen A,Scarfe GB,Scott JS,Smith JM,Steward OR,Terstiege I,Tucker MJ,Turner P,Wilkinson SD,Wrigley GL,

更新日期：2020-12-01 00:00:00

abstract：:Modified oligonucleotides, whose ON-OFF switch of hybridization can be controlled by an external stimulus, are important to understanding life phenomena and efficient treatment of diseases. The ON-OFF switch can be completely controlled by chemical modification of the oligonucleotide such as cyclization. However, thei...

journal_title：Bioorganic & medicinal chemistry

authors： Nishizawa S,Ohkubo A

更新日期：2020-12-01 00:00:00

abstract：:Antibiotic resistance among clinically significant bacterial pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. As a pa...

journal_title：Bioorganic & medicinal chemistry

authors： Song D,Bi F,Zhang N,Qin Y,Liu X,Teng Y,Ma S

更新日期：2020-11-01 00:00:00

abstract：:Alternative splicing of the androgen receptor (AR) is frequently observed in castration resistant prostate cancer (CRPC). One AR isoform, the AR-V7 splice variant, is a constitutively active transcription factor which lacks a ligand binding domain and is therefore undruggable. AR-V7 expression correlates with resistan...

journal_title：Bioorganic & medicinal chemistry

authors： Melnyk JE,Steri V,Nguyen HG,Hann B,Feng FY,Shokat KM

更新日期：2020-10-15 00:00:00

abstract：:A series of allosteric kidney-type glutaminase (GLS) inhibitors possessing a mercaptoethyl (SCH2CH2) linker were synthesized in an effort to further expand the structural diversity of chemotypes derived from bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a prototype allosteric inhibitor of GLS. ...

journal_title：Bioorganic & medicinal chemistry

authors： Duvall B,Zimmermann SC,Gao RD,Thomas AG,Kalčic F,Veeravalli V,Elgogary A,Rais R,Rojas C,Le A,Slusher BS,Tsukamoto T

更新日期：2020-10-15 00:00:00

abstract：:The therapy of chronic hepatitis C virus infections has significantly improved with the development of direct-acting antivirals (DAAs), which contain NS3/4A protease, NS5A, and NS5B polymerase inhibitors. However, mutations in specific residues in these viral target genes are associated with resistance to the DAAs. Es...

journal_title：Bioorganic & medicinal chemistry

authors： Li X,Han J,Lee HW,Yoon YS,Jin Y,Khadka DB,Yang S,Kim M,Cho WJ

更新日期：2020-10-01 00:00:00

abstract：:Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue...

journal_title：Bioorganic & medicinal chemistry

authors： González-Naranjo P,Pérez C,Girón R,Sánchez-Robles EM,Martín-Fontelles MI,Carrillo-López N,Martín-Vírgala J,Naves M,Campillo NE,Páez JA

更新日期：2020-10-01 00:00:00

abstract：:We have synthesized several conformationally constrained dipeptide analogues as possible substrates for incorporation into proteins. These have included three cyclic dipeptides formed from Boc derivatives of 2,4-diaminobutyric acid, ornithine and lysine, having 5-, 6-, and 7-membered lactam rings, respectively. These ...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang C,Bai X,Dedkova LM,Hecht SM

更新日期：2020-09-23 00:00:00

abstract：:WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a fin...

journal_title：Bioorganic & medicinal chemistry

authors： Chen D,Tian L,Po KHL,Chen S,Li X

更新日期：2020-09-15 00:00:00

abstract：:Antisense oligonucleotides (AS-ODNs) specifically hybridize with target mRNAs, resulting in interference with the splicing mechanism or the regulation of protein translation. In our previous reports, we demonstrated that β-glucan schizophyllan (SPG) can form a complex with AS-ODNs attached with oligo deoxyadenosine dA...

journal_title：Bioorganic & medicinal chemistry

authors： Sasaki S,Izumi H,Morimoto Y,Sakurai K,Mochizuki S

更新日期：2020-09-15 00:00:00

abstract：:Histone deacetylases (HDACs) have been found to be biomarkers of cancers and the corresponding inhibitors have attracted much attention these years. Herein we reported a near-infrared fluorescent HDAC inhibitor based on vorinostat (SAHA) and a NIR fluorophore. This newly designed inhibitor showed similar inhibitory ac...

journal_title：Bioorganic & medicinal chemistry

authors： Huang Y,Ru HB,Bao B,Yu JH,Li J,Zang Y,Lu W

更新日期：2020-09-01 00:00:00

abstract：:Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues ("fleximers") of the FDA-approved nucleoside Acyclovir that exhibit activ...

journal_title：Bioorganic & medicinal chemistry

authors： Thames JE,Waters CD 3rd,Valle C,Bassetto M,Aouadi W,Martin B,Selisko B,Falat A,Coutard B,Brancale A,Canard B,Decroly E,Seley-Radtke KL

更新日期：2020-08-31 00:00:00

abstract：:The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid replacement. However, systematic assessment of acid surrogates is often time consuming and expensive, while prediction of both physicochemical properties (logP and logD) as well as acidity would be desirable at early discovery...

journal_title：Bioorganic & medicinal chemistry

authors： Ferri M,Alunno M,Greco FA,Mammoli A,Saluti G,Carotti A,Sardella R,Macchiarulo A,Camaioni E,Liscio P

更新日期：2020-08-28 00:00:00

abstract：:Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDP...

journal_title：Bioorganic & medicinal chemistry

authors： Goetz DB,Varney ML,Wiemer DF,Holstein SA

更新日期：2020-08-15 00:00:00

abstract：:c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients scre...

journal_title：Bioorganic & medicinal chemistry

authors： Lin Q,Zhang Y,Fu Z,Hu B,Si Z,Zhao Y,Shi H,Cheng D

更新日期：2020-08-01 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesi...

journal_title：Bioorganic & medicinal chemistry

authors： Li Q,Li J,Cai Y,Zou Y,Chen B,Zou F,Mo J,Han T,Guo W,Huang W,Qiu Q,Qian H

更新日期：2020-08-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) constitute the largest protein superfamily in the human genome. GPCRs play key roles in mediating a wide variety of physiological events including proliferation and cancer metastasis. Given the major roles that GPCRs play in mediating cancer growth, they present promising targets fo...

journal_title：Bioorganic & medicinal chemistry

authors： Paciaroni NG,Norwood VM 4th,Ratnayake R,Luesch H,Huigens RW 3rd

更新日期：2020-07-15 00:00:00

abstract：:Photodynamic therapy (PDT) is a non-invasive, selective, and cost-effective cancer therapy. We previously reported that thiophene-based organic D-π-A sensitizers consist of an electron-donating (D) moiety, a π-conjugated bridge (π) moiety, and an electron-accepting (A) moiety, and are readily accessible and stable tem...

journal_title：Bioorganic & medicinal chemistry

authors： Fuse S,Moriya W,Sato S,Nakamura H

更新日期：2020-07-01 00:00:00

abstract：:Conflicts with the notion that specific substrate interactions were required in the control of reaction path in active transport systems, P-glycoprotein showed extraordinarily low specificity. Therefore, overexpression P-glycoprotein excluded a large number of anticancer agents from cancer cells, and multidrug resista...

journal_title：Bioorganic & medicinal chemistry

authors： Xu W,Chen S,Wang X,Wu H,Yamada H,Hirano T

更新日期：2020-06-15 00:00:00

abstract：:New series of benzimidazole ring core conjugated with either dithiocarbamate or thiopropyl linkers, hybridized with different secondary amines were synthesized; 5-15 and 22-31; respectively. The new compounds were characterized by different spectroscopic techniques (1H, 13C 1D & 2D NMR, ESI-MS and IR). They were scree...

journal_title：Bioorganic & medicinal chemistry

authors： Nashaat S,Henen MA,El-Messery SM,Eisa H

更新日期：2020-06-01 00:00:00

abstract：:Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has potent apoptosis-inducing effect on human leukemia HL-60 cells. Erypoegin K has a chiral carbon at the C-2'' position of its furan ring and naturally occurs as a racemic mixture of (S)- and (R)-isomers. In the present study, we semi-s...

journal_title：Bioorganic & medicinal chemistry

authors： Hikita K,Saigusa S,Takeuchi Y,Matsuyama H,Nagai R,Kato K,Murata T,Tanaka H,Wagh YS,Asao N,Kaneda N

更新日期：2020-06-01 00:00:00

abstract：:In our previous work, a series of 2-amino-3,4-dihydroquinazoline derivativesusing an electron acceptor group was reported to be potent T-type calcium channel blockers and exhibit strong cytotoxic effects against various cancerous cell lines. To investigate the role of the guanidine moiety in the 2-amino-3,4-dihydroqui...

journal_title：Bioorganic & medicinal chemistry

authors： Nam Y,Ryu KD,Jang C,Moon YH,Kim M,Ko D,Chung KS,Gandini MA,Lee KT,Zamponi GW,Lee JY

更新日期：2020-06-01 00:00:00

abstract：:Friedreich's Ataxia (FRDA) is an incurable genetic disease caused by an expanded trinucleotide AAG repeat within intronic RNA of the frataxin (FXN) gene. We have previously demonstrated that synthetic antisense oligonucleotides or duplex RNAs that are complementary to the expanded repeat can activate expression of FXN...

journal_title：Bioorganic & medicinal chemistry

authors： Shen X,Wong J,Prakash TP,Rigo F,Li Y,Napierala M,Corey DR

更新日期：2020-06-01 00:00:00

abstract：:Six new polyketides aplojaveediins A-F (1-6) were isolated from the endophytic fungus Aplosporella javeedii associated with the host plant Orychophragmus violaceus (Brassicaceae). The structures of the new metabolites were elucidated by analysis of their NMR and MS data. Compound 1 exhibited antifungal activity agains...

journal_title：Bioorganic & medicinal chemistry

authors： Gao Y,Wang L,Kalscheuer R,Liu Z,Proksch P

更新日期：2020-05-15 00:00:00

abstract：:Selections from dynamic combinatorial libraries (DCL) benefit from the dynamic nature of the library that can change constitution upon addition of a selection pressure, such as ligands binding to a protein. This technology has been predominantly used with small molecules interacting with each other through reversible ...

journal_title：Bioorganic & medicinal chemistry

authors： Farrera-Soler L,Daguer JP,Raunft P,Barluenga S,Imberty A,Winssinger N

更新日期：2020-05-15 00:00:00