Abstract:
:Two 1,4-benzoquinone derivatives, found in the venom of the scorpion Diplocentrus melici following exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio)cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization and biological assays. The red benzoquinone is effective against Staphylococcus aureus [minimum inhibitory concentration (MIC) = 4 µg/mL], while the blue benzoquinone is active against Mycobacterium tuberculosis (MIC = 4 µg/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects.
journal_name
Proc Natl Acad Sci U S Aauthors
Carcamo-Noriega EN,Sathyamoorthi S,Banerjee S,Gnanamani E,Mendoza-Trujillo M,Mata-Espinosa D,Hernández-Pando R,Veytia-Bucheli JI,Possani LD,Zare RNdoi
10.1073/pnas.1812334116subject
Has Abstractpub_date
2019-06-25 00:00:00pages
12642-12647issue
26eissn
0027-8424issn
1091-6490pii
1812334116journal_volume
116pub_type
杂志文章abstract::Corazonin is a highly conserved neuropeptide hormone of wide-spread occurrence in insects yet is associated with no universally recognized function. After discovery of the corazonin receptor in Drosophila, we identified its ortholog in the moth, Manduca sexta, as a prelude to physiological studies. The corazonin recep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0305291101
更新日期:2004-04-27 00:00:00
abstract::c-myc, N-myc, and L-myc genes are subject to highly variable degrees of tissue-specific regulation. Their aberrant expression has also been implicated in the pathogenesis of a variety of malignant tumors. The recently identified max protein dimerizes with c-myc to promote its sequence-specific DNA binding. max exists ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.3.960
更新日期:1993-02-01 00:00:00
abstract::Aquaporin (AQP) 4 is the predominant water channel in the mammalian brain, abundantly expressed in the blood-brain and brain-cerebrospinal fluid interfaces of glial cells. Its function in cerebral water balance has implications in neuropathological disorders, including brain edema, stroke, and head injuries. The 1.8-A...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0902725106
更新日期:2009-05-05 00:00:00
abstract::Retinoic acid is a morphogenetic signaling molecule derived from vitamin A and involved in vertebrate development. Two groups of receptors, retinoic acid receptors and retinoid X receptors (RXRs), have been identified. All-trans-retinoic acid is the high-affinity ligand for retinoic acid receptors, and 9-cis-retinoic ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.13.6170
更新日期:1993-07-01 00:00:00
abstract::Highly purified globin mRNA from ducks was copied with RNA-directed DNA polymerase from avian myeloblastosis virus into anti-messenger DNA. With excess RNA, more than 90% of this DNA annealed back to its template with a C(o)t/2 value of 7.5 x 10(-4) mol.sec. liter(-1); the melting temperature of the hybrid was 86 degr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.4.1122
更新日期:1973-04-01 00:00:00
abstract::Metal cation homeostasis is essential for plant nutrition and resistance to toxic heavy metals. Many plant metal transporters remain to be identified at the molecular level. In the present study, we have isolated AtNramp cDNAs from Arabidopsis and show that these genes complement the phenotype of a metal uptake defici...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.9.4991
更新日期:2000-04-25 00:00:00
abstract::The Xlim-1 gene is activated in the late blastula stage of Xenopus embryogenesis in the mesoderm, and its RNA product becomes concentrated in the Spemann organizer at early gastrula stage. A major regulator of early expression of Xlim-1 is activin or an activin-like signal. We report experiments aiming to identify the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.18.9717
更新日期:1997-09-02 00:00:00
abstract::Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine-like and chemokine-like activities. We show here that, although plasma Trx levels are unrelated to survival of HIV-infected individuals with CD4 cell counts above 200/microl blood, survival is significantly impaired (P = 0.003) when plasma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.041624998
更新日期:2001-02-27 00:00:00
abstract::Eleven amino acid positions in the helix-turn-helix of lambda repressor have been mutagenized by using a combinatorial method in which alanine is substituted at each position with a probability of 0.5. Approximately 25% of the 2048 proteins in the resulting binomial library are active, including some variants with as ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.9.4246
更新日期:1993-05-01 00:00:00
abstract::In most organisms, light plays a key role in the synchronization of the circadian timing system with the environmental day-night cycle. Light pulses that phase-shift the circadian clock also induce the expression of period (per) genes in vertebrates. Here, we report the cloning of a zebrafish per gene, zfper4, which i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0305436101
更新日期:2004-03-23 00:00:00
abstract::The N-terminal arginine-rich motif of phage HK022 Nun protein binds to NUT sequences in phage lambda nascent transcripts and induces transcription termination. Interactions between the Nun C terminus and RNA polymerase as well as the DNA template are required for termination. We have isolated Nun C-terminal point and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0430995100
更新日期:2003-04-29 00:00:00
abstract::Genetic and biochemical studies on enzymes known to be involved in regulating DNA supercoiling yield a complex spectrum of effects on the Escherichia coli SOS system. Previous studies indicated that only inhibition of DNA gyrase by antibiotics that act on the DNA gyrase A subunit results in turning on the E. coli SOS ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.9.2510
更新日期:1983-05-01 00:00:00
abstract::Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their inn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1200705109
更新日期:2012-10-16 00:00:00
abstract::pRK212.2, a derivative of the broad host range plasmid RK2, contains two EcoRI cleavage fragments, A and B, neither of which can replicate by itself in Escherichia coli. Fragment A (41.7 kilobases), but not fragment B (14.4 kilobases), can be cloned by insertion into the unrelated plasmids mini-F and ColE1. Fragment B...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.4.1648
更新日期:1979-04-01 00:00:00
abstract::The carboxy-terminal domain (CTD) code encrypted within the Y1S2P3T4S5P6S7 heptad repeats of RNA polymerase II (Pol2) is deeply rooted in eukaryal biology. Key steps to deciphering the code are identifying the events in gene expression that are governed by individual "letters" and then defining a vocabulary of multile...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1810711115
更新日期:2018-11-06 00:00:00
abstract::Early conformational events during folding of acyl-CoA binding protein (ACBP), an 86-residue alpha-helical protein, were explored by using a continuous-flow mixing apparatus with a dead time of 70 micros to measure changes in intrinsic tryptophan fluorescence and tryptophan-dansyl fluorescence energy transfer. Althoug...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.152321499
更新日期:2002-07-23 00:00:00
abstract::The ability of estrogens to stimulate the transcriptional activity of the estrogen receptor can be inhibited by a diverse range of estrogen antagonists. Here we show that the antiestrogen ICI 164,384, N-(n-butyl)-11-[3,17 beta-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl]N-methylundecanamide, rapidly reduces the levels ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.9.4037
更新日期:1992-05-01 00:00:00
abstract::Evidence is presented that suggests that GTP (or 5'-guanylylmethylene diphosphonate) is not essential for either formation of an AUG-directed, initiation factor IF-2-dependent initiation complex on the 30S subunit or for positioning of fMet-tRNA on the peptidyl site. However, recycling of limiting amounts of IF-2 requ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.10.2770
更新日期:1972-10-01 00:00:00
abstract::The three members of the Brn-3 family of POU domain transcription factors are found in highly restricted sets of central nervous system neurons. Within the retina, these factors are present only within subsets of ganglion cells. We show here that in the developing mouse retina, Brn-3b protein is first observed in pres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.9.3920
更新日期:1996-04-30 00:00:00
abstract::Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, they did not uncover the collective behaviors or patterns of the genes. We h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.242597199
更新日期:2002-12-10 00:00:00
abstract::SUMO, a small ubiquitin-related modifier, is known to covalently attach to a number of nuclear regulatory proteins such as p53, IkappaB, promyelocytic leukemia protein and c-Jun. The sumoylation reaction is catalyzed by the SUMO protease, which exposes the C-terminal active glycine residue of the nascent SUMO, the het...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402889101
更新日期:2004-06-08 00:00:00
abstract::Given the slow unfolding of what may become catastrophic changes to Earth's climate, many are understandably distraught by failures of public policy to rise to the magnitude of the challenge. Few in the science community would think to question the scientific response to the unfolding changes. However, is the science ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906691116
更新日期:2019-12-03 00:00:00
abstract::Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera, detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1614864114
更新日期:2017-03-07 00:00:00
abstract::Metals in one spatial dimension are described at the lowest energy scales by the Luttinger liquid theory. It is well understood that this free theory, and even interacting integrable models, can support ballistic transport of conserved quantities including energy. In contrast, realistic one-dimensional metals, even wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1916213117
更新日期:2020-06-09 00:00:00
abstract::Membrane vesicles were extracted from etiolated and light-grown plants, a plant cell suspension culture, and an alga. Upon addition of ATP and Mg(2+), active Ca(2+) uptake into the vesicles against a concentration gradient was shown. The dependence of this uptake on ATP and Mg(2+) concentrations, pH, and temperature i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.3.1232
更新日期:1978-03-01 00:00:00
abstract::We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plast...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1218682110
更新日期:2013-03-19 00:00:00
abstract::Antibodies previously used for immunofluorescence localization of a myosin heavy chain-like polypeptide to the nuclear envelope in higher eukaryotic cells crossreact with both muscle and nonmuscle isoforms of Drosophila myosin heavy chain. Analyses of Drosophila tissue culture cells and premyogenic embryos suggest tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.1.219
更新日期:1991-01-01 00:00:00
abstract::Mutations are introduced into rearranged Ig variable genes at a frequency of 10(-2) mutations per base pair by an unknown mechanism. Assuming that DNA repair pathways generate or remove mutations, the frequency and pattern of mutation will be different in variable genes from mice defective in repair. Therefore, hyperm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.12.6953
更新日期:1998-06-09 00:00:00
abstract::The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1601485113
更新日期:2016-08-02 00:00:00
abstract::VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (MI). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1018925108
更新日期:2011-02-01 00:00:00