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41.
Sébastien L. Degorce Rana Anjum Keith S. Dillman Lisa Drew Sam D. Groombridge Christopher T. Halsall Eva M. Lenz Nicola A. Lindsay Michele F. Mayo Jennifer H. Pink Graeme R. Robb James S. Scott Stephen Stokes Yafeng Xue 《Bioorganic & medicinal chemistry》2018,26(4):913-924
We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic. Further optimisation of substituents on this pyrrolotriazine core culminated with the discovery of 30 as a promising in vivo probe to assess the potential of IRAK4 inhibition for the treatment of MyD88 mutant DLBCL in combination with a BTK inhibitor. When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib. 相似文献
42.
Mohammad Attaullah Masarrat J. Yousuf Sohail Shaukat Syed Ishtiaq Anjum Mohammad Javed Ansari Islam Dad Buneri Muhammad Tahir Muhammad Amin Naveed Ahmad Shahid Ullah Khan 《Saudi Journal of Biological Sciences》2018,25(7):1284-1290
Organochlorine pesticides (OCPs) are frequently used worldwide as insecticides, fungicides, herbicides and termiticides and have been associated with a variety of cancers in animal and human studies. In the present study, we examined residues of fourteen OCPs in the serum samples of diagnosed cancer patients and healthy residents of Karachi, Pakistan. A random collection of fasting blood samples was carried out from the donors with informed consent. Serum was separated within 2?h of blood collection and was then subjected to extraction with organic solvents followed by purification with florisil column. The final organic extract of each serum sample was processed with Gas Chromatograph coupled with Electron Capture Detector (GC-ECD). OCPs were detected in 97.59% of the cancer cases and 93.75% of the healthy subjects. Mean concentrations of total OCPs (ΣOCPs) was found elevated in the cancer group (0.606?mg/kg) compared with the control group (0.322?mg/kg). Endosulfan was the highest prevalent OCP with a mean concentration of 0.214?mg/kg in the cancer group and 0.166?mg/kg in the control group. The second most prevalent OCP was 4,4-DDE with a mean concentration of 0.131?mg/kg in the cancer group and 0.019?mg/kg in the control group. Highest level of ΣOCPs was detected in the breast cancer cases (20.411?mg/kg) with a mean level of (2.041?mg/kg). In light of the obtained results and available literature on the subject, it has been concluded that OCPs are positively associated with the risk of various cancers in humans. 相似文献
43.
Iram Shahzadi Muhammad Iqbal Rizwan Rasheed M. Arslan Ashraf Shagufta Perveen Makhdoom Hussain 《Acta Physiologiae Plantarum》2017,39(8):173
The study was conducted to assess whether selenium (Se) application modulates fertility to alter grain yield in bread wheat grown under different moisture regimes. Seeds of wheat cultivar Millat-2011 were sown in the plots using a randomized complete block design with three replicates per treatment. After germination, the plants were exposed to six moisture regimes, viz. no irrigation after germination, irrigation at boot stage, irrigations at boot and grain-filling stages, irrigations at crown root, boot and grain-filling stages, irrigations at crown root, boot, heading and grain-filling stages and irrigations at crown root, stem elongation, boot, heading and grain-filling stages. At the heading stage, foliar spray of sodium selenate (0, 2 and 4 mg Se L?1) was done. Withholding water at early growth stages significantly increased oxidative stress and decreased growth and grain yield. Irrespective of moisture regimes, foliar application of Se (2 mg L?1) decreased oxidative stress, modulated photosynthetic pigments and fertility and increased grain yield in wheat. The Se-mediated increase in grain yield was attributed to the increase in chlorophyll and ascorbic acid contents and fertility coupled with decrease of oxidative stress under different moisture regimes. The results could be helpful to manage wheat production in the semi-arid environments. 相似文献
44.
Hasina Perveen Moumita Dash Shamima Khatun Moulima Maity Syed Sirajul Islam Sandip Chattopadhyay 《Biochemistry and Biophysics Reports》2017
Momordica charantia (MC) fruit known as bitter gourd, is of potential nutritional and medicinal value. The objectives of the present in vitro study were to evaluate the efficacy of bioactive pectic polysaccharides (CCPS) of MC along with another well-known bioactive compound curcumin in the abrogation of hepatocellular oxidative stress persuaded by sodium arsenite. Electrozymographic method was developed for the assessment of superoxide dismutase (SOD) and catalase activities of liver tissues maintained under an in vitro system. A significant association of CCPS of MC in combination with curcumin was found in the alleviation of oxidative stress induced by sodium arsenite in liver slice. Generated data pointed out that CCPS of MC and curcumin separately or in combination can offer significant protection against alterations in malondialdehyde (MDA), conjugated diene (CD) and antioxidative defense (SOD, CAT) markers. Furthermore, results of hepatic cell DNA degradation strongly supported that both these co-administrations have efficacy in preventing cellular damage. This is the first information of extracted polysaccharides from MC preventing arsenic induced damage in a liver slice of rat. 相似文献
45.
Jabbar A Rashid MH Javed MR Perveen R Malana MA 《Journal of industrial microbiology & biotechnology》2008,35(6):515-524
Gymnoascella citrina produced two isoforms of endoglucanases (CMCase-I and -capital I, Ukrainiancapital I, Ukrainian) under solid-state condition. Purified CMCase-I was novel because it was apparently holoenzyme in nature. The enzyme was monomeric as its native and subunit mass were almost the same, i.e., 43 and 42 kDa, respectively. Ea for carboxymethylcellulose (CMC) hydrolysis was 36.2 kJ mol(-1). The enzyme was stable over a pH range of 3.5-6.5, while temperature optimum was 55 degrees C. Vmax, Km and k (cat )for CMC hydrolysis were 39 U mg(-1) protein, 6.25 mg CMC mL(-1) and 27.5 s(-1), respectively. The pKa1 and pKa2 of ionizable groups of active site were 2.8 and 7.4, respectively. Thermodynamic parameters for CMC hydrolysis were as follows: DeltaH*=33.5 kJ mol(-1), DeltaG*=70.42 kJ mol(-1) and DeltaS*=-114.37 J mol(-1) K(-1). The removal of metals resulted into complete loss of enzymatic activity and was completely recovered in the presence of 1 mM Mn2+, whereas inhibition initiated at 5 mM. The other metals like Ca2+, Zn2+ and K1+ showed no inhibition up to 7 mM, Co2+ completely inhibited the activity, while Mg2+ could not recover the initial activity up to 7 mM. So we are reporting for the first time, kinetics and thermodynamics of CMCase-Iota from G. citrina. 相似文献
46.
A new series of complexes of cobalt(II) fluoride, nickel(II) fluoride, copper(II) fluoride and zinc(II) fluoride with imidazole were synthesized and characterized by elemental analysis, molar conductance, magnetic moments, IR and electronic absorption measurements. Based on elemental and spectral data, the complexes were found to be of [M(im)6]F2 · XH2O type, where M is Co(II), Ni(II), Cu(II) and Zn(II) and X 4-5. The magnetic moments and spectral data suggested that all the complexes possessed an octahedral geometry. The crystal structure of the nickel complex, [Ni(im)6]F2 · 5H2O, is also reported in which nickel atom is surrounded by six nitrogen atoms of imidazole. Strong intra- and inter-molecular hydrogen bonding exists between fluoride ions (uncoordinated), nitrogen of imidazole and the -OH of water molecules. 相似文献
47.
Khalid Mohammed Khan Momin Khan Muhammad Ali Muhammad Taha Saima Rasheed Shahnaz Perveen M. Iqbal Choudhary 《Bioorganic & medicinal chemistry》2009,17(22):7795-7801
Bis-Schiff bases 1–27 have been synthesized and their in vitro antiglycation potential has been evaluated. Compounds 21 (IC50 = 243.95 ± 4.59 μM), 20 (IC50 = 257.61 ± 5.63 μM), and 7 (IC50 = 291.14 ± 2.53 μM) showed an excellent antiglycation activity better than the standard (rutin, IC50 = 294.46 ± 1.50 μM). This study has identified a series of potential molecules as antiglycation agents. A structure–activity relationship has been studied, and all the compounds were characterized by spectroscopic techniques. 相似文献
48.
Khalid M. Khan Sumayya Saeed Muhammad Ali Madiha Gohar Javariya Zahid Ambreen Khan Shahnaz Perveen M. Iqbal Choudhary 《Bioorganic & medicinal chemistry》2009,17(6):2447-2451
A series of unsymmetrically disubstituted urea derivatives 1–28 has been synthesized and screened for their antiglycation activity in vitro. Compounds 26 (IC50 = 4.26 ± 0.25 μM), 1 (IC50 = 5.8 ± 0.08 μM), 22 (IC50 = 4.26 ± 0.25 μM), 6 (IC50 = 6.4 ± 0.02 μM), 5 (IC50 = 6.6 ± 0.26 μM), 2 (IC50 = 7.02 ± 0.31 μM), 3 (IC50 = 7.14 ± 0.84 μM), 27 (IC50 = 7.27 ± 0.36 μM), 4 (IC50 = 8.16 ± 1.04 μM), 21 (IC50 = 8.4 ± 0.15 μM), 23 (IC50 = 9.0 ± 0.35 μM) and 13 (IC50 = 15.22 ± 6.7 μM) showed an excellent antiglycation activity far better than the standard (rutin, IC50 = 41.9 ± 2.3 μM). This study thus provides a series of potential molecules for further studies of antiglycation agents. 相似文献
49.
William Matlock Kevin K. Chau Manal AbuOun Emma Stubberfield Leanne Barker James Kavanagh Hayleah Pickford Daniel Gilson Richard P. Smith H. Soon Gweon Sarah J. Hoosdally Jeremy Swann Robert Sebra Mark J. Bailey Timothy E. A. Peto Derrick W. Crook Muna F. Anjum Daniel S. Read A. Sarah Walker Nicole Stoesser Liam P. Shaw REHAB consortium 《The ISME journal》2021,15(8):2322
F-type plasmids are diverse and of great clinical significance, often carrying genes conferring antimicrobial resistance (AMR) such as extended-spectrum β-lactamases, particularly in Enterobacterales. Organising this plasmid diversity is challenging, and current knowledge is largely based on plasmids from clinical settings. Here, we present a network community analysis of a large survey of F-type plasmids from environmental (influent, effluent and upstream/downstream waterways surrounding wastewater treatment works) and livestock settings. We use a tractable and scalable methodology to examine the relationship between plasmid metadata and network communities. This reveals how niche (sampling compartment and host genera) partition and shape plasmid diversity. We also perform pangenome-style analyses on network communities. We show that such communities define unique combinations of core genes, with limited overlap. Building plasmid phylogenies based on alignments of these core genes, we demonstrate that plasmid accessory function is closely linked to core gene content. Taken together, our results suggest that stable F-type plasmid backbone structures can persist in environmental settings while allowing dramatic variation in accessory gene content that may be linked to niche adaptation. The association of F-type plasmids with AMR may reflect their suitability for rapid niche adaptation.Subject terms: Environmental microbiology, Genomics 相似文献
50.
Metal/metalloid stress tolerance in plants: role of ascorbate,its redox couple,and associated enzymes 总被引:1,自引:0,他引:1
Naser A. Anjum Sarvajeet S. Gill Ritu Gill Mirza Hasanuzzaman Armando C. Duarte Eduarda Pereira Iqbal Ahmad Renu Tuteja Narendra Tuteja 《Protoplasma》2014,251(6):1265-1283
The enhanced generation of reactive oxygen species (ROS) under metal/metalloid stress is most common in plants, and the elevated ROS must be successfully metabolized in order to maintain plant growth, development, and productivity. Ascorbate (AsA) is a highly abundant metabolite and a water-soluble antioxidant, which besides positively influencing various aspects in plants acts also as an enigmatic component of plant defense armory. As a significant component of the ascorbate-glutathione (AsA-GSH) pathway, it performs multiple vital functions in plants including growth and development by either directly or indirectly metabolizing ROS and its products. Enzymes such as monodehydroascorbate reductase (MDHAR, EC 1.6.5.4) and dehydroascorbate reductase (DHAR, EC 1.8.5.1) maintain the reduced form of AsA pool besides metabolically controlling the ratio of AsA with its oxidized form (dehydroascorbate, DHA). Ascorbate peroxidase (APX, EC 1.11.1.11) utilizes the reduced AsA pool as the specific electron donor during ROS metabolism. Thus, AsA, its redox couple (AsA/DHA), and related enzymes (MDHAR, DHAR, and APX) cumulatively form an AsA redox system to efficiently protect plants particularly against potential anomalies caused by ROS and its products. Here we present a critical assessment of the recent research reports available on metal/metalloid-accrued modulation of reduced AsA pool, AsA/DHA redox couple and AsA-related major enzymes, and the cumulative significance of these antioxidant system components in plant metal/metalloid stress tolerance. 相似文献