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21.
Adnan A. Bekhit Eskedar T. Lodebo Ariaya Hymete Hanan M. Ragab Salma A. Bekhit Kikuko Amagase Afnan Batubara Mohammed A. S. Abourehab Alaa El-Din A. Bekhit Tamer M. Ibrahim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2320
Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1. 相似文献
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Pseudomonas aeruginosa (P. aeruginosa) is a highly pathogenic bacteria involved in numerous diseases among which, are urinary tract infections (UTIs). The pyocyanin secreted as a virulence factor by this bacterium has many beneficial applications but its high cost remains an obstacle for its widespread use. In this study, a total of fifty urine isolates were identified as P. aeruginosa. All strains produced pyocyanin pigment with a range of 1.3–31 µg/ml. The highest producer clinical strain P21 and the standard strain PA14 were used in optimization of pyocyanin production. Among tested media, king’s A fluid medium resulted in the highest yield of pyocyanin pigment followed by nutrient broth. Growth at 37 °C was superior in pyocyanin production than growth at 30 °C. Both shaking and longer incubation periods (3–4 days) improved pyocyanin production. The pyocyanin yield was indifferent upon growth of P21 at both pH 7 and pH 8. In conclusion, the optimum conditions for pyocyanin production are to use King’s A fluid medium of pH 7 and incubate the inoculated medium at 37 °C with shaking at 200 rpm for a period of three to four days. 相似文献
25.
Axonal guidance signals are transduced through growth cone surface receptors to the interior leading to changes of actin dynamics
and actin binding proteins, which are critical in determining the outcome of actin cytoskeleton reorganization. We report
here the characterization of the Drosophila actin binding protein abLIM/Unc-115 homolog Dunc-115 and its role in the nervous system. Three Dunc-115 isoforms are identified
as Dunc-115L, M and S, respectively. While Dunc-115L is a canonical homolog of Unc-115 with four LIM domains and one villin
headpiece domain, Dunc-115M and S are novel isoforms without counterparts in other species. Our molecular modeling shows Dunc-115L
is likely to bind to actin. Mutant analysis reveals that Dunc-115 is involved in axonal projection in both the visual and
central nervous system. 相似文献
26.
The kinetics of microbial degradation of naphthalene from a two-component non-aqueous-phase liquid (NAPL) coated onto uniformly sized nonporous particles were evaluated in a completely mixed batch reactor (CMBR) system and in flow-through column systems to examine the differences in the biodegradation kinetic coefficients, micro(max), the maximum specific growth rate coefficient, and K(s), the half saturation constant in the two systems. The values of these coefficients were estimated by nonlinear least-squares regression of the naphthalene mineralization profiles obtained from both CMBR and column biodegradation experiments. The results show that the range of values for micro(max) and K(s) obtained from column systems are very similar to the range of values obtained from CMBR systems. This suggests that coefficients estimated from CMBR or column systems are equally applicable for modeling studies. The presence of microorganisms and the development of biofilms at the NAPL-water interface reduced the mass transfer rates of naphthalene from the NAPL by 60% in CMBR and by 70% in column systems. If such changes in mass transfer coefficients are not accounted for, significantly erroneous values of biokinetic coefficients may be obtained. 相似文献
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Jizhou Yan Xiang Yang Mark A. Mortin Mohammed Shahabuddin 《Genesis (New York, N.Y. : 2000)》2009,47(3):196-203
Malaria kills a million people annually. Understanding the relationship between a causative parasite, Plasmodium falciparum, and the mosquito vector might suggest novel prevention approaches. We created and transformed into Drosophila two genes encoding, thrombospondin‐related adhesive protein (TRAP) and circumsporozoite protein (CSP), found on the cell surface of Plasmodium sporozoites. To understand a model insect's response, we induced these proteins separately and together, performing whole genome microarray analysis measuring gene expression changes. Gene ontology classification of responding genes reveals that TRAP and CSP strongly and differentially influence Drosophila genes involved with cell motility and gene regulation, respectively; however, the most striking effects are on the immune system. While immune‐related genes are but modestly elevated compared with responses to sepsis, there is a marked repression of the Toll pathway. This suggests: (1) how Plasmodium infection of the mosquito might use TRAP and CSP to modulate the host insect's physiology to promote sporozoite survival and transmission to man and (2) that approaches to elevate expression of the mosquito's Toll pathway might lead to novel methods of malaria prevention. genesis 47:196–203, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
29.
Shoeb M Laloraya M Kumar PG 《Biochemical and biophysical research communications》2004,316(3):763-770
A peptidomics approach was applied to determine the peptides in the larval central nervous system of the grey flesh fly, Neobellieria bullata. Fractions obtained by high performance liquid chromatography were analysed by MALDI-TOF and ESI-Q-TOF mass spectrometry. This provided biochemical evidence for the presence of 18 neuropeptides, 11 of which were novel Neobellieria peptides. Most prominently present were the FMRFamide-related peptides: 7 FMRFamides, 1 FIRFamide, and Neb-myosuppressin. The three putative capa-gene products Neb-pyrokinin and the periviscerokinins Neb-PVK-1 and -2 were detected, as well as another pyrokinin. This Neb-PK-2 was also present in the ring gland along with corazonin, Neb-myosuppressin, and Neb-AKH-GK, an intermediate processing product of the adipokinetic hormone. Furthermore, the central nervous system contained Neb-LFamide, proctolin, and FDFHTVamide, designated as Neb-TVamide. With this study, we considerably increased our knowledge of the neuropeptidome of the pest fly N. bullata, which is an important insect model for physiological research. 相似文献
30.
I Bruce M Akhlaq GC Bloomfield E Budd B Cox B Cuenoud P Finan P Gedeck J Hatto JF Hayler D Head T Keller L Kirman C Leblanc DL Grand C McCarthy D O'Connor C Owen MS Oza G Pilgrim NE Press L Sviridenko L Whitehead 《Bioorganic & medicinal chemistry letters》2012,22(17):5445-5450
Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK. 相似文献