Bioorganic & medicinal chemistry

Publisher: Elsevier


  • Impact factor
  • 5-year impact
  • Cited half-life
  • Immediacy index
  • Eigenfactor
  • Article influence
  • Other titles
    Bioorganic & medicinal chemistry (En ligne), Bioorganic and medicinal chemistry
  • ISSN
  • OCLC
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers
    • Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository
    • Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists
    • Set statement to accompany deposit
    • Published source must be acknowledged
    • Must link to journal home page or articles' DOI
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PMC after 12 months
    • Authors who are required to deposit in subject repositories may also use Sponsorship Option
    • Pre-print can not be deposited for The Lancet
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: A modular synthesis of L-proline derived peptidomimetics has been developed using the CuI catalyzed Huisgen cycloaddition between an azido prolinamide with pyridine and benzene dicarboxamide containing dialkynes. Förster Resonance Energy Transfer (FRET) melting assay provided an initial indication that the pyridyl analogue can stabilize the c-KIT1 quadruplex DNA. A competitive FRET-melting assay and Fluorescent Intercalator Displacement (FID) assay suggest that the pyridyl ligand shows excellent selectivity for c-KIT1 quadruplex over duplex DNA and other investigated G-quadruplexes. Molecular docking studies indicate that the pyridyl ligand can adopt unique conformations upon binding to c-KIT1 quadruplex due to the presence of intramolecular hydrogen bonds. The pyridyl ligand can perturb cell cycle progression and induce necrotic cell death of human hepatocellular liver carcinoma HepG2 cells.
    Bioorganic & medicinal chemistry 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC50 = 21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC50 values 21.4 ± 1.04 and 21.5 ± 0.61μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and 1HNMR.
    Bioorganic & medicinal chemistry 06/2014; 22.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel α, β-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A2 (sPLA2), cyclooxygenases (COX), soyabean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-α. Six α, β-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14) exhibited strong inhibition of sPLA2 activity, with IC50 values in the range of 2.19 to 8.76 μM. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with IC50 values ranging from 0.37 to 1.77 μM (lower than that of reference compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All compounds were evaluated for the inhibitory activities against LPS-induced TNF-α and IL-6 release in the macrophages. On the basis of screening results, five active compounds 3, 4, 12, 13 and 14 were found strong inhibitors of TNF-α and IL-6 release in a dose-dependent manner. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX and LOX inhibitory activities of the investigated compounds. Present findings increases the possibility that these α, β-unsaturated carbonyl based compounds might serve as beneficial starting point for the design and development of improved anti-inflammatory agents.
    Bioorganic & medicinal chemistry 06/2014; In press.
  • Bioorganic & medicinal chemistry 05/2014; 22:3449-3454..
  • [Show abstract] [Hide abstract]
    ABSTRACT: Valinol is part of numerous pharmaceuticals and has various other important applications. Optically pure valinol (ee >99%) was prepared employing different w-transaminases from the corresponding prochiral hydroxy ketone. By the choice of the enzyme the (R)- as well as the (S)- enantiomer were accessible. Reductive amination was performed in organic solvent (MTBE) using 2-propyl amine as amine donor whereas alanine was applied in or in aqueous medium. Transformations in phosphate buffer were successfully performed even at 200 mM substrate concentration (20.4 g/L) leading to 99% (R) and 94% (S) conversion with perfect optical purity (>99% ee).
    Bioorganic & medicinal chemistry 05/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of 6-chloro-3-oxindole derivatives 1-25 were synthesized in high yields by the reaction of 6-chlorooxindole with different aromatic aldehydes in the presence of piperidine. All the synthesized compounds were isolated with E configuration. The structures were confirmed using spectroscopic techniques, including (1)H NMR and EIMS. These compounds showed varying degree of yeast α-glucosidase inhibition and seven were found as potent inhibitors of the enzyme. Compounds 2, 3, 4, 5, 6, 23, and 25 exhibited IC50 values 2.71±0.007, 11.41±0.005, 37.93±0.002, 15.19±0.004, 24.71±0.007, 17.33±0.001, and 14.2±0.002μM, respectively, as compared to standard acarbose (IC50, 38.25±0.12μM). Docking studies helped to find interactions between the enzyme and the active compounds. As a result of this study, oxindoles have been discovered as a new class of α-glucosidase inhibitors which have not been reported earlier.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The marine alkaloid norzoanthamine is a candidate drug for osteoporosis treatment. Due to its structural complexity, simplified analogues possessing similar biological activities are needed for further research. Recently, we found that the bisaminal unit, representing two-thirds of the original structure, is a bioactive equivalent. We synthesized three kinds of further truncated norzoanthamines and evaluated their collagen protection activities. No analog with collagen protection activity comparable to that of the bisaminal unit was found. Thus, we confirmed the importance of the bisaminal unit for the collagen protection activity. Furthermore, we found that the recognition tolerance of the substrate collagen is relatively large by comparing both enantiomers.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heterotrimeric G-proteins are the immediate downstream effectors of G-protein coupled receptors (GPCRs). Endogenous protein guanine nucleotide dissociation inhibitors (GDIs) like AGS3/4 and RGS12/14 function through GPR/Goloco GDI domains. Extensive characterization of GPR domain peptides indicate they function as selective GDIs for Gαi by competing for the GPCR and Gβγ and preventing GDP release. We modified a GPR consensus peptide by testing FGF and TAT leader sequences to make the peptide cell permeable. FGF modification inhibited GDI activity while TAT preserved GDI activity. TAT-GPR suppresses G-protein coupling to the receptor and completely blocked α2-adrenoceptor (α2AR) mediated decreases in cAMP in HEK293 cells at 100nM. We then sought to discover selective small molecule inhibitors for Gαi. Molecular docking was used to identify potential molecules that bind to and stabilize the Gαi-GDP complex by directly interacting with both Gαi and GDP. Gαi-GTP and Gαq-GDP were used as a computational counter screen and Gαq-GDP was used as a biological counter screen. Thirty-seven molecules were tested using nucleotide exchange. STD NMR assays with compound 0990, a quinazoline derivative, showed direct interaction with Gαi. Several compounds showed Gαi specific inhibition and were able to block α2AR mediated regulation of cAMP. In addition to being a pharmacologic tool, GDI inhibition of Gα subunits has the advantage of circumventing the upstream component of GPCR-related signaling in cases of overstimulation by agonists, mutations, polymorphisms, and expression-related defects often seen in disease.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The coenzyme A (CoA) biosynthetic enzymes have been used to produce various CoA analogues, including mechanistic probes of CoA-dependent enzymes such as those involved in fatty acid biosynthesis. These enzymes are also important for the activation of the pantothenamide class of antibacterial agents, and of a recently reported family of antibiotic resistance inhibitors. Herein we report a study on the selectivity of pantothenate kinase, the first and rate limiting step of CoA biosynthesis. A robust synthetic route was developed to allow rapid access to a small library of pantothenate analogs diversified at the β-alanine moiety, the carboxylate or the geminal dimethyl group. All derivatives were tested as substrates of Escherichia coli pantothenate kinase (EcPanK). Four derivatives, all N-aromatic pantothenamides, proved to be equivalent to the benchmark N-pentylpantothenamide (N5-pan) as substrates of EcPanK, while two others, also with N-aromatic groups, were some of the best substrates reported for this enzyme. This collection of data provides insight for the future design of PanK substrates in the production of useful CoA analogues.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Proteasome inhibitors are currently a focus of increased attention as anticancer drug candidates. We recently performed systematic structure-activity relationship studies of the peptidic natural product belactosin A and identified non-peptidic derivative 2 as a highly potent proteasome inhibitor. However, the cell growth inhibitory effect of 2 is only moderate, probably due to the biologically unstable β-lactone warhead. Peptide epoxyketones are an important class of proteasome inhibitors exhibit high potency in cellular systems based on the efficient α,β-epoxyketone warhead. Importantly, belactosin derivatives bind primarily to the primed binding site, while peptide epoxyketones bind only to the non-primed binding site of proteasome, suggesting that hybridization of them might lead to the development of a new class of proteasome inhibitors. Thus, we successfully identified a novel chemotype of proteasome inhibitors 3 and 4 by rational structure-based design, which are expected to bind to both the primed and non-primed binding sites of proteasome.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The dopamine D4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD4 receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D4 receptor. Compound 27 (KiD4=0.84nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D4 receptor. Compound 28 (KiD4=3.9nM) while not as potent, was more discriminatory for the D4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT1AR and 5HT2BR, have binding affinity constants better than 100nM (Ki <100nM). Compound 28 is a potentially useful D4-selective ligand for probing disease treatments involving the D4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Platinum(II) octaethylporphyrin (PtOEP)-loaded organic-inorganic hybrids were obtained via the microwave-assisted sol-gel condensation with methyltrimethoxysilane and poly(vinylpyrrolidone). From transparent and homogeneous hybrid films, the strong phosphorescence from PtOEP was observed. Next, the resulting hybrids were immersed in the aqueous buffer, and the emission intensity was monitored by changing the dissolved oxygen level in the buffer. When the hybrid with relatively-higher amount of the silica element, the strong phosphorescence was observed even under the aerobic conditions. In contrast, the emission from the hybrids with lower amounts of the silica element was quenched under the hypoxic conditions. This is, to the best of our knowledge, the first example to demonstrate that the responsiveness of the phosphorescence intensity of PtOEP in hybrid films to the dissolved oxygen concentration in water can be modulated by changing the percentage of the contents in the material.
    Bioorganic & medicinal chemistry 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of cancer grows annually worldwide and in Brazil it is the second cause of death. The search for anti-cancer drugs has then become urgent. It depends on the studies of natural and chemical synthesis products. The antitumor action of LQB-118, a pterocarpanquinone structurally related to lapachol, has been demonstrated to induce mechanisms linked to leukemia cell apoptosis. This work investigated some mechanisms of the in vitro antitumor action of LQB-118 on prostate cancer cells. LQB-118 reduced the expression of the c-Myc transcription factor, downregulated the cyclin D1 and cyclin B1 mRNA levels and upregulated the p21 cell cycle inhibitor. These effects resulted in cell cycle arrest in the S and G2/M phases and inhibition of tumor cell proliferation. LQB-118 also induced programmed cell death of the prostate cancer cells, as evidenced by internucleosomal DNA fragmentation and annexin-V positive cells. Except the cell cycle arrest in the S phase and enhanced c-Myc expression, all the mechanisms observed here for the in vitro antitumor action of LQB-118 were also found for Paclitaxel, a traditional antineoplastic drug. These findings suggest new molecular mechanisms for the LQB-118 in vitro antitumor action.
    Bioorganic & medicinal chemistry 04/2014;

Related Journals