abstract：:Current techniques for the identification of DNA adduct-inducing and DNA interstrand crosslinking agents include electrophoretic crosslinking assays, electrophoretic gel shift assays, DNA and RNA stop assays, mass spectrometry-based methods and 32P-post-labelling. While these assays provide considerable insight into t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Medan J,Sleebs BE,Lackovic K,Watson KG,Evison BJ,Phillips DR,Cutts SM

更新日期：2021-01-21 00:00:00

abstract：:SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol ext...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee YE,Kodama T,Win NN,Ki DW,Hoang NN,Wong CP,Lae KZW,Ngwe H,Dairi T,Morita H

更新日期：2021-01-15 00:00:00

abstract：:The search for new antimicrobial agents is greater than ever due to the perpetual threat of multidrug resistance in known pathogens and the relentless emergence of new infections. In this manuscript, ten thiazole-based thiazolidinone hybrids bearing a 6-trifluoromethoxy substituent on the benzothiazole core were synth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Haroun M,Tratrat C,Petrou A,Geronikaki A,Ivanov M,Ciric A,Sokovic M

更新日期：2021-01-15 00:00:00

abstract：:An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mecha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng CB,Gao WC,Pang PP,Ma X,Peng LC,Yang L,Li X

更新日期：2021-01-11 00:00:00

abstract：:Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou D,Lou Z,Lin Y,Shangguan H,Lin Y,Luo Q,Zhang H,Lin G,Chen R,Kou L,Bao S

更新日期：2020-12-17 00:00:00

abstract：:Myelin is a lipid multilayer involved in the rate of nerve transmission, and its loss is a pathological feature of multiple sclerosis in brains. Since in vivo imaging of myelin may be useful for drug development, early diagnosis, and monitoring the disease stage, we designed, synthesized, and evaluated eight novel rad...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watanabe H,Sakai S,Iikuni S,Shimizu Y,Shirakawa H,Kaneko S,Ono M

更新日期：2020-12-15 00:00:00

abstract：:PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody dr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holte D,Lyssikatos JP,Valdiosera AM,Swinney Z,Sisodiya V,Sandoval J,Lee C,Aujay MA,Tchelepi RB,Hamdy OM,Gu C,Lin B,Sarvaiya H,Pysz MA,Laysang A,Williams S,Jun Lee D,Holda MK,Purcell JW,Gavrilyuk J

更新日期：2020-12-15 00:00:00

abstract：:The synthesis of a lead anti-viral cyclopropyl carboxy acyl hydrazone 4F17 (5) and three sequential arrays of structural analogues along with the initial assessment and optimization of the antiviral pharmacophore against the herpes simplex virus type 1 (HSV-1) are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Babu Dokuburra C,D'Aiuto L,Demers M,McClain L,Piazza P,Williamson K,Zheng W,Nimgaonkar VL

更新日期：2020-12-15 00:00:00

abstract：:Xanthorrhizol, isolated from the Indonesian Java turmeric Curcuma xanthorrhiza, displays broad-spectrum antibacterial activity. We report herein the evidence that mechanism of action of xanthorrhizol may involve FabI, an enoyl-(ACP) reductase, inhibition. The predicted Y156V substitution in the FabI enzyme promoted xa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yogiara,Mordukhova EA,Kim D,Kim WG,Hwang JK,Pan JG

更新日期：2020-12-15 00:00:00

abstract：:Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baugh SDP,Chaly A,Weaver DG,Pelletier JC,Thanna S,Freeman KB,Reitz AB,Scott RW

更新日期：2020-12-13 00:00:00

abstract：:Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer origin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumata K,Zhang Y,Ogawa M,Kurihara Y,Mori W,Hu K,Fujinaga M,Nengaki N,Zhang MR

更新日期：2020-12-01 00:00:00

abstract：:N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barberis C,Erdman P,Czekaj M,Fire L,Pribish J,Tserlin E,Maniar S,Batchelor JD,Liu J,Patel VF,Hebert A,Levit M,Wang A,Sun F,Huang SA

更新日期：2020-12-01 00:00:00

abstract：:A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Am...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang JM,Kwon SO,Ann J,Blumberg PM,Ha H,Yoo YD,Frank-Foltyn R,Lesch B,Bahrenberg G,Stockhausen H,Christoph T,Lee J

更新日期：2020-12-01 00:00:00

abstract：:Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sampath Kumar HM,Herrmann L,Tsogoeva SB

更新日期：2020-12-01 00:00:00

abstract：:This work describes a set of discovery research studies of an influenza cap-dependent endonuclease (CEN) inhibitor with a carbamoyl pyridone bicycle (CAB) scaffold. Using influenza CEN inhibitory activity, antiviral activity and pharmacokinetic (PK) parameters as indices, structure activity relationships (SAR) studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Taoda Y,Miyagawa M,Akiyama T,Tomita K,Hasegawa Y,Yoshida R,Noshi T,Shishido T,Kawai M

更新日期：2020-11-15 00:00:00

abstract：:Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a nov...

journal_title：Bioorganic & medicinal chemistry letters

authors： Daher SS,Franklin KP,Scherzi T,Dunman PM,Andrade RB

更新日期：2020-11-01 00:00:00

abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

更新日期：2020-11-01 00:00:00

abstract：:A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Eagon S,Hammill JT,Bach J,Everson N,Sisley TA,Walls MJ,Durham S,Pillai DR,Falade MO,Rice AL,Kimball JJ,Lazaro H,DiBernardo C,Kiplin Guy R

更新日期：2020-11-01 00:00:00

abstract：:The pentacyclic triterpene 3β,6β,16β-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Silva-Filho CJA,Freitas PGC,Oliveira FCE,Barbosa FG,Oliveira MCF,Eloy JO,Pessoa C,Mafezoli J

更新日期：2020-10-15 00:00:00

abstract：:A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh A,Sharma S,Arora S,Attri S,Kaur P,Kaur Gulati H,Bhagat K,Kumar N,Singh H,Vir Singh J,Mohinder Singh Bedi P

更新日期：2020-10-15 00:00:00

abstract：:A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keith JM,Jones W,Pierce JM,Seierstad M,Palmer JA,Webb M,Karbarz M,Scott BP,Wilson SJ,Luo L,Wennerholm M,Chang L,Rizzolio M,Rynberg R,Chaplan S,Guy Breitenbucher J

更新日期：2020-10-15 00:00:00

abstract：:The complex of the recombinant fusion protein of apoPholasin and glutathione S-transferase (GST-apoPholasin) with non-fluorescent dehydrocoelenterazine (dCTZ) (GST-apoPholasin/dCTZ complex) shows yellow fluorescence at 539 nm by excitation at 430 nm. The GST-apoPholasin/dCTZ complex with a fluorophore (dCTZ*) has cons...

journal_title：Bioorganic & medicinal chemistry letters

authors： Inouye S,Nakamura M,Taguchi J,Hosoya T

更新日期：2020-10-01 00:00:00

abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

更新日期：2020-10-01 00:00:00

abstract：:In an effort to discover oral inverse agonists of RORγt to treat inflammatory diseases, a new 2,6-difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfone tem...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Jiang B,Lu Z,Stachura S,Weigelt CA,Sack JS,Khan J,Ruzanov M,Wu DR,Yarde M,Shen DR,Zhao Q,Salter-Cid LM,Carter PH,Murali Dhar TG

更新日期：2020-10-01 00:00:00

abstract：:Glucose transporters (GLUTs) facilitate glucose uptake and are overexpressed in most cancer cells. Inhibition of glucose transport has been shown to be an effective method to slow the growth of cancer cells both in vitro and in vivo. We have previously reported on the anticancer activity of an ester derived glucose up...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roberts DA,Wang L,Zhang W,Liu Y,Shriwas P,Qian Y,Chen X,Bergmeier SC

更新日期：2020-09-15 00:00:00

abstract：:Emergence of antibioresistance is currently a major threat of public health worldwide. Hence there is an urge need of finding new antibacterial material. Herein, we report a simple and eco-friendly method to synthesize homo and heterodicationic ionic liquids based on quaternary phosphonium and ammonium salt. In order ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brunel F,Lautard C,Garzino F,Raimundo JM,Bolla JM,Camplo M

更新日期：2020-09-15 00:00:00

abstract：:Herein we report the preparation of 3,4-dibenzylfurans and some oxidized derivatives with lignan backbone. The compounds were prepared using the Friedel-Crafts reaction with BF3 etherate as catalyst, demethylation with iodocyclohexane, acetylation and oxidation reactions. The antimicrobial activity was evaluated throu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tufano I,Buommino E,Iesce MR,De Filippis A,Grieco P,Lembo F,DellaGreca M

更新日期：2020-09-01 00:00:00

abstract：:Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dack KN,Johnson PS,Henriksson K,Eirefelt S,Carnerup MA,Stahlhut M,Ollerstam AK

更新日期：2020-09-01 00:00:00

abstract：:P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

更新日期：2020-09-01 00:00:00

abstract：:The our previous study synthesized the chrysin-chromene-spirooxindole hybrids 3, and further found compound 3e had good antitumor activity against A549 cells in vitro through multi-target co-regulation of the p53 signalling pathway to inhibit the proliferation of A549 cells. This study was designed to evaluate the ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang WH,Chen S,Liu XL,Bing-Lin,Liu XW,Zhou Y

更新日期：2020-09-01 00:00:00

abstract：:Two new trichothecene sesquiterpenes, trichobreols D (1) and E (2), were isolated from the culture broth of marine-derived Trichoderma cf. brevicompactum together with trichobreol A (3). The structures of 1 and 2 were assigned on the basis of their spectroscopic data. Compound 1 inhibited the growth of two yeast-like ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamazaki H,Yagi A,Takahashi O,Yamaguchi Y,Saito A,Namikoshi M,Uchida R

更新日期：2020-09-01 00:00:00

abstract：:Modifications at C6 and C7 positions of 3-cyanoquinolines 6 and 7 led to potent inhibitors of the ErbB family of kinases particularly against EGFRWT and Her4 enzymes in the radioisotope filter binding assay. The lead (4, SAB402) displayed potent dual biochemical activities with EGFRWT/Her4 IC50 ratio of 80 due to its ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mansour TS,Pallepati RR,Basetti V

更新日期：2020-08-15 00:00:00

abstract：:The transcription factor ΔFosB accumulates in response to chronic insults such as drugs of abuse, L-3,4-dihydroxyphenylalanine (l-DOPA) or stress in specific regions of the brain, triggering long lasting neural and behavioral changes that underlie aspects of drug addiction, dyskinesia, and depression. Thus, small mole...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Y,Liu Z,Aglyamova G,Chen J,Chen H,Bhandari M,White MA,Rudenko G,Zhou J

更新日期：2020-08-15 00:00:00

abstract：:As part of the presented research, thirteen new aminoalkanol derivatives were designed and obtained by chemical synthesis. In vivo studies (mice, i.p.) showed anticonvulsant activity (MES) of nine compounds, and in the case of one compound (R,S-trans-2-((2-(2,3,5-trimethylphenoxy)ethyl)amino)cyclohexan-1-ol, 4) both a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pańczyk K,Rapacz A,Furgała-Wojas A,Sałat K,Koczurkiewicz-Adamczyk P,Łucjanek M,Skiba-Kurek I,Karczewska E,Sowa A,Żelaszczyk D,Siwek A,Popiół J,Pękala E,Marona H,Waszkielewicz A

更新日期：2020-08-15 00:00:00

abstract：:TGF-β type I receptor (also known as activin-like kinase 5 or ALK5) plays a critical role in the progression of fibrotic diseases and tumor invasiveness and metastasis, as well. The development of small inhibitors targeting ALK5 has been validated as a potential therapeutic strategy for fibrotic diseases and cancer. H...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tan B,Zhang X,Quan X,Zheng G,Li X,Zhao L,Li W,Li B

更新日期：2020-08-15 00:00:00

abstract：:Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation,  a phenomenon termed as "austerity". Search for the new agents that eliminate the toler...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tawila AM,Sun S,Kim MJ,Omar AM,Dibwe DF,Ueda JY,Toyooka N,Awale S

更新日期：2020-08-15 00:00:00

abstract：:A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： El-Shafey HW,Gomaa RM,El-Messery SM,Goda FE

更新日期：2020-08-01 00:00:00

abstract：:Small molecule JAK inhibitors have been demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu K,Wu W,Zhang C,Liu Z,Xiao B,Yuan Z,Li A,Chen D,Zhai X,Jiang Y

更新日期：2020-07-15 00:00:00

abstract：:Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A...

journal_title：Bioorganic & medicinal chemistry letters

authors： Woo SY,Lee KS,Shin HL,Kim SH,Lee MJ,Young Kim H,Ham H,Lee DJ,Choi SW,Seo WD

更新日期：2020-07-15 00:00:00

abstract：:We previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with 64Cu (64Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of 64Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pyo A,You SH,Sik Kim H,Young Kim J,Min JJ,Kim DY,Hong Y

更新日期：2020-07-15 00:00:00