Mechanism-based inhibitors of serine proteases with high selectivity through optimization of S' subsite binding.

abstract：:V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing...

journal_title：Bioorganic & medicinal chemistry

authors： Niculescu-Duvaz D,Niculescu-Duvaz I,Suijkerbuijk BM,Ménard D,Zambon A,Nourry A,Davies L,Manne HA,Friedlos F,Ogilvie L,Hedley D,Takle AK,Wilson DM,Pons JF,Coulter T,Kirk R,Cantarino N,Whittaker S,Marais R,Springer CJ

更新日期：2010-09-15 00:00:00

abstract：:Thirteen anthraquinone derivatives 5-17 including two 3-(3-alkylaminopropoxy)-9,10-anthraquinone (NHA) derivatives 5 and 6, and 11 1-hydroxy-3-(3-alkylaminopropoxy)-9,10-anthraquinone (MHA) derivatives 7-17 were synthesized, evaluated for cytotoxicities against two cancer cell lines, and assayed the generation of reac...

journal_title：Bioorganic & medicinal chemistry

authors： Tu HY,Huang AM,Teng CH,Hour TC,Yang SC,Pu YS,Lin CN

更新日期：2011-09-15 00:00:00

abstract：:Polyamides consisting of N-methylpyrrole (Py), N-methylimidazole (Im), and N-methyl-3-hydroxypyrrole (Hp) are synthetic ligands that recognize predetermined DNA sequences with affinities and specificities comparable to many DNA-binding proteins. As derivatives of the natural products distamycin and netropsin, Py/Im/Hp...

journal_title：Bioorganic & medicinal chemistry

authors： Bremer RE,Szewczyk JW,Baird EE,Dervan PB

更新日期：2000-08-01 00:00:00

abstract：:We have examined the efficiency of DNA photooxidation in DNA/PNA duplex and DNA/(PNA)(2) triplex for the first time. DNA/PNA duplex was cleaved at GG steps by external riboflavin with high efficiency like specific GG cleavage in DNA/DNA duplex. However, the 5'G selectivity of the GG oxidation in DNA/PNA duplex was muc...

journal_title：Bioorganic & medicinal chemistry

authors： Okamoto A,Tanabe K,Dohno C,Saito I

更新日期：2002-03-01 00:00:00

abstract：:Resveratrol (3,5,4'-trans-trihydroxystibene) is a natural phytoalexin present in grapes and red wine, which possesses a variety of biological activities including antioxidant activity. In order to find more active antioxidant with resveratrol as the lead compound we synthesized 4,4'-dihydroxy-trans-stilbene (4,4'-DHS)...

journal_title：Bioorganic & medicinal chemistry

authors： Fan GJ,Liu XD,Qian YP,Shang YJ,Li XZ,Dai F,Fang JG,Jin XL,Zhou B

更新日期：2009-03-15 00:00:00

abstract：:Synthesis of [(11)C]celecoxib, a selective COX-2 inhibitor, and [(11)C]SC-62807, a major metabolite of celecoxib, were achieved and the potential of these PET probes for assessing the function of drug transporter in biliary excretion was evaluated. The synthesis of [(11)C]celecoxib was achieved in one-pot by reacting ...

journal_title：Bioorganic & medicinal chemistry

authors： Takashima-Hirano M,Takashima T,Katayama Y,Wada Y,Sugiyama Y,Watanabe Y,Doi H,Suzuki M

更新日期：2011-05-01 00:00:00

abstract：:Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human ca...

journal_title：Bioorganic & medicinal chemistry

authors： Su CR,Yeh SF,Liu CM,Damu AG,Kuo TH,Chiang PC,Bastow KF,Lee KH,Wu TS

更新日期：2009-08-15 00:00:00

abstract：:A new series of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes were designed and synthesized. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Sixteen of these new compounds exhibited comparable or better anti-inflammatory activities than aspirin...

journal_title：Bioorganic & medicinal chemistry

authors： Bi L,Zhao M,Gu K,Wang C,Ju J,Peng S

更新日期：2008-02-15 00:00:00

abstract：:Nine anionic water-soluble calix[4]arene species, incorporating sulfonate, carboxylate or phosphonate groups, six of them incorporating two 2,2'-bithiazole subunits in alternate position at the lower rim, have been synthesised and evaluated as anti-HIV agents on various HIV strains and cells of the lymphocytic lineage...

journal_title：Bioorganic & medicinal chemistry

authors： Mourer M,Psychogios N,Laumond G,Aubertin AM,Regnouf-de-Vains JB

更新日期：2010-01-01 00:00:00

abstract：:A protein-cleaving catalyst highly selective for a disease-related protein can be used as a catalytic drug. As the first protein-cleaving catalyst selective for a protein substrate, a catalyst for myoglobin (Mb) was designed by attaching the Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinato...

journal_title：Bioorganic & medicinal chemistry

authors： Jeon JW,Son SJ,Yoo CE,Hong IS,Suh J

更新日期：2003-07-03 00:00:00

abstract：:Griseofulvin is a fungal metabolite and antifungal drug used for the treatment of dermatophytosis in both humans and animals. Recently, griseofulvin and its analogues have attracted renewed attention due to reports of their potential anticancer effects. In this study griseofulvin (1) and related analogues (2-6, with 4...

journal_title：Bioorganic & medicinal chemistry

authors： Paguigan ND,Al-Huniti MH,Raja HA,Czarnecki A,Burdette JE,González-Medina M,Medina-Franco JL,Polyak SJ,Pearce CJ,Croatt MP,Oberlies NH

更新日期：2017-10-15 00:00:00

abstract：:Nuclear factor-kappaB (NF-kappaB) has been considered as a good target for the treatment of many diseases. Although a lot of NF-kappaB inhibitors have already been reported, many of them have several common problems. Thus, we attempted to identify novel NF-kappaB inhibitors to be unique lead compounds for creating new...

journal_title：Bioorganic & medicinal chemistry

authors： Kobayashi T,Yoshimori A,Kino K,Komori R,Miyazawa H,Tanuma SI

更新日期：2009-07-15 00:00:00

abstract：:We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" di...

journal_title：Bioorganic & medicinal chemistry

authors： Amano Y,Umezawa N,Sato S,Watanabe H,Umehara T,Higuchi T

更新日期：2017-02-01 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：:We investigated acid-catalyzed rearrangement of thebaine 14 and its N-propyl analog 15 with methanesulfonic acid in the presence of the nucleophiles methanethiol and hydrogen sulfide. R(-)-2-methylthioapocodeine 16, R(-)-2-methylthioapomorphine 18, and their N-n-propyl analogs 17, 19 were obtained by rearrangement in ...

journal_title：Bioorganic & medicinal chemistry

authors： Tóth M,Berényi S,Csutorás C,Kula NS,Zhang K,Baldessarini RJ,Neumeyer JL

更新日期：2006-03-15 00:00:00

abstract：:The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K(i)=25 microM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xe...

journal_title：Bioorganic & medicinal chemistry

authors： Krehan D,Frølund B,Ebert B,Nielsen B,Krogsgaard-Larsen P,Johnston GA,Chebib M

更新日期：2003-11-17 00:00:00

abstract：:In vitro studies, using combined spectrophotometry and oximetry together with hplc/ms examination of the products of tyrosinase action demonstrate that hydroquinone is not a primary substrate for the enzyme but is vicariously oxidised by a redox exchange mechanism in the presence of either catechol, L-3,4-dihydroxyphe...

journal_title：Bioorganic & medicinal chemistry

authors： Stratford MR,Ramsden CA,Riley PA

更新日期：2012-07-15 00:00:00

abstract：:MARCH-INSIDE methodology was applied to the prediction of the bitter tasting threshold of 48 dipeptides by means of pattern recognition techniques, in this case linear discriminant analysis (LDA), and regression methods. The LDA models yielded a percentage of good classification higher than 80% with the two main famil...

journal_title：Bioorganic & medicinal chemistry

authors： Ramos de Armas R,González Díaz H,Molina R,Pérez González M,Uriarte E

更新日期：2004-09-15 00:00:00

abstract：:AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G(4)T(4)G(4)) int...

journal_title：Bioorganic & medicinal chemistry

authors： Huang J,Wang M,Zhou Y,Weng X,Shuai L,Zhou X,Zhang D

更新日期：2009-11-15 00:00:00

abstract：:Nuclear receptors, especially the peroxisome proliferator activated receptors (PPARs) and the farnesoid X receptor (FXR) fulfill crucial roles in metabolic balance. Their activation offers valuable therapeutic potential which has high clinical relevance with the fibrates and glitazones as PPAR agonistic drugs. With gr...

journal_title：Bioorganic & medicinal chemistry

authors： Merk D,Lamers C,Weber J,Flesch D,Gabler M,Proschak E,Schubert-Zsilavecz M

更新日期：2015-02-01 00:00:00

abstract：:Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

journal_title：Bioorganic & medicinal chemistry

authors： Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

更新日期：2010-03-01 00:00:00

abstract：:Plants of the genera Ferula and Ferulago are known for their complex content in bioactive secondary metabolites such as coumarins, phenylpropanoids, and sesquiterpenes. We used the ground parts of Ferula communis subsp. communis, Ferula glauca subsp. glauca and Ferulago campestris as natural sources for the isolation ...

journal_title：Bioorganic & medicinal chemistry

authors： Dall'Acqua S,Linardi MA,Maggi F,Nicoletti M,Petitto V,Innocenti G,Basso G,Viola G

更新日期：2011-10-01 00:00:00

abstract：:The problems inherent in the enzymatic and chemical synthesis of S-adenosyl-L-methionine (SAM) led us to develop an efficient, simple method for the synthesis of large amounts of labeled SAM. Previously, we reported that the problem of product inhibition of E. coli SAM synthetase encoded by the metK gene was successfu...

journal_title：Bioorganic & medicinal chemistry

authors： Park J,Tai J,Roessner CA,Scott AI

更新日期：1996-12-01 00:00:00

abstract：:The objective of this brief review is to present an overview of the bioorganic chemistry of cyclic-ADP-ribose (cADPR) with special emphasis on the methodology used for the synthesis of analogues of cADPR. New structural analogues of cADPR can be prepared using either the biomimetic method or ADP-ribosyl cyclase from A...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang FJ,Gu QM,Sih CJ

更新日期：1999-05-01 00:00:00

abstract：:Acid-catalyzed transacetalation of dimethyl (2R,3S)-2,3-dimercapto-succinate and 1,1,3,3-tetramethoxypropane provided cis-4,5-dimethoxycarbonyl-2-(2',2'-dimethoxyethyl)-1,3-dithiolane (2) in 77% yield. The esterification of 2 and l-amino acids provided 18 active antitumor cis-2-carbonylmethyl-4,5- di(l-aminoacyloxymet...

journal_title：Bioorganic & medicinal chemistry

authors： Huang F,Zhao M,Zhang X,Wang C,Qian K,Kuo RY,Morris-Natschke S,Lee KH,Peng S

更新日期：2009-08-15 00:00:00

abstract：:A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging from ...

journal_title：Bioorganic & medicinal chemistry

authors： Giri R,Goodell JR,Xing C,Benoit A,Kaur H,Hiasa H,Ferguson DM

更新日期：2010-02-15 00:00:00

abstract：:Antibiotic resistance remains a major global public health threat that requires sustained discovery of novel antibacterial agents with unexploited scaffolds. Structure-activity relationship of the first-generation aryl isonitrile compounds we synthesized led to an initial lead molecule that informed the synthesis of a...

journal_title：Bioorganic & medicinal chemistry

authors： Kyei-Baffour K,Mohammad H,Seleem MN,Dai M

更新日期：2019-05-01 00:00:00

abstract：:Tyrosinase is known as the key enzyme for melanin biosynthesis, which is effective in preventing skin injury by ultra violet (UV). In past decades, tyrosinase has been well studied in the field of cosmetics, medicine, agriculture and environmental sciences, and a lot of tyrosinase inhibitors have been developed for th...

journal_title：Bioorganic & medicinal chemistry

authors： Oyama T,Takahashi S,Yoshimori A,Yamamoto T,Sato A,Kamiya T,Abe H,Abe T,Tanuma SI

更新日期：2016-09-15 00:00:00

abstract：:Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2)=0.77; R(2)=0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size....

journal_title：Bioorganic & medicinal chemistry

authors： Freitas RF,Oprea TI,Montanari CA

更新日期：2008-01-15 00:00:00

abstract：:Analogues of the anti-tuberculosis drug bedaquiline, bearing a 3,5-dimethoxy-4-pyridyl C-unit, retain high anti-bacterial potency yet exert less inhibition of the hERG potassium channel, in vitro, than the parent compound. Two of these analogues (TBAJ-587 and TBAJ-876) are now in preclinical development. The present s...

journal_title：Bioorganic & medicinal chemistry

authors： Sutherland HS,Tong AST,Choi PJ,Blaser A,Franzblau SG,Cooper CB,Upton AM,Lotlikar M,Denny WA,Palmer BD

更新日期：2020-01-01 00:00:00