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11.
Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist
Srinivas Bandaru Vijaya Kumar Marri Priyadarshani Kasera Purnima Kovuri Amandeep Girdhar Deepti Raj Mittal Sabeen Ikram Ravi GV Anuraj Nayarisseri 《Bioinformation》2014,10(10):652-657
Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short
as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2
agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to
lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were
retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of
cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085
(Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure
CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN
9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation. 相似文献
12.
13.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献
14.
Ibragimova MI Petukhov VIu Zheglov EP Koniukhov GV Nizamov RN 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2004,44(5):529-534
The effect of radiotoxin (RT) obtained from y-irradiated potato tubes on blood of sheep and mice has been investigated by using in vitro and ex vivo EPR. In experiments in vitro, the action of different preparations (RT, extract from unirradiated potato tubers, 1%-HCl or 30%-hydrogen peroxide) on sheep blood has been compared. It has been established that RT is an effective oxidant (like 1%-HCl) of haem iron that leads to an increase of the methemoglobin concentration. The specific peculiarity of RT effect on blood in vitro is an appearance of two well-resolved lines from methemoglobin belonging, probably, to different paramagnetic centers. The signal from nonspecific complexes of Fe3+ has been also observed. Ex vivo EPR spectra markedly differ from these obtained in experiments in vitro. An additional line with g approximately 2.005 and width 6 G in 30 minutes after intraperitoneal RT injection in the lethal dose (0.2 ml of preparation containing of 2 mg RT) has been revealed. Subsequent intoxication of mice is accompanied by the appearance of the signal from nitrosyl complexes in EPR spectra. These differences in experimental results of in vitro and ex vivo EPR can be explained by launch of compensatory adaptive response of organism on the action of highly toxic preparation. 相似文献
15.
First generation (G1) hairs in mice homozygous for the wellhaarig (we) gene are wavy and shorter than in normal mice; basal regions of the hairs are deformed. Follicles of G1 hairs in mid-dorsal region of 8-, 12- and 16-days old we/we mice were examined. Huxley cells of the inner root sheath (IRS) in apical region of hair follicles appeared to be hypertrophied. Cytoplasm of these cells was not stained by basic dyes and showed no birefringence. Cytoplasm of the IRS Henle cells was not stained by basic dyes either. These data indicate that keratinization of the IRS cells is disturbed in mutant homozygotes. The layer of outer root sheath in the we/we mice was thinner than in normal mice; this is probably due to hypertrophy of the IRS cells. The structure of differentiating cells of the hair shaft in normal and mutant mice was similar. The data obtained suggest that abnormal G1 hairs in we/we mice result from disturbance in IRS cells differentiation. 相似文献
16.
The autosomal recessive gene hairless (hr) is responsible for the complete hairlessness in mice homozygous for this gene. Hair shedding that begins at the age of 10 days is caused by an abnormal cycle of hair follicle development disturbed at the catagen stage. This results in enhanced programmed cell death (apoptosis) and ultimately leads to the complete hair follicle destruction and shedding of all hairs by the age of three weeks. To study the phenotypic expression of the hr gene in a chimeric organism, we have obtained 12 chimeric mice hr/hr <--> +/+ by means of aggregation of early embryos hr/hr and +/+. In chimeric mice, the hair shedding has begun two days later than in the hr/hr mice. By day 23 of postnatal development, hairless areas were present on the coat of chimeric mice or the latter were completely hairless depending on the percentage of the hr/hr mutant component. In four chimeras with high content of the mutant component (68-76%), the hair shedding process was similar to that in the hr/hr mice, though it was accomplished two days later. In three chimeras with 48-51% of the mutant component, alternating hairless and hair-covered bands were observed. These data suggest that the hr gene acts in epidermal cells of a hair follicle, because epidermal cell clones in embryonic skin migrate in the lateral-ventral direction coherently and without mixing. However, some chimeras displayed a pattern which was not so clear-cut: the band borders were illegible and hairs partly covered the hairless areas. In some chimeras, the uniform thinning of the coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice differing in the ratio between mutant (hr/hr) and normal (+/+) components in tissues suggests that the hr gene acts in the epidermal cells of the hair follicle. The interactions between cells have an essential effect on the mode and degree of the hr gene expression, which leads to distortion of the "ectodermal" coat pattern in chimeras. 相似文献
17.
18.
Leukemia inhibitory factor (LIF) improves and prolongs the development of parthenogenetic mouse embryos 总被引:2,自引:0,他引:2
We studied the effect of the growth factor LIF on the development of parthenogenetic mouse embryos (CBA x C57BL/6)F1. LIF was added to the culture medium at 10, 50, 100, and 250 ng/ml at the morula stage and parthenogenetic embryos were cultivated in vitro until the late blastocysts stage and then transplanted in the uterus of pseudopregnant females, which were then sacrificed on day 12 of pregnancy. All the LIF doses used improved the development of parthenogenetic mouse embryos at the preimplantation stages and increased the amount of blastocysts by 16%, on average, as compared to the control. LIF at 50 and 100 ng/ml increased approximately twice the number of embryos that reached the somatic stages. Some of them reached the stage of 32-45 somites and had fore and hind limb buds. No such embryos were found in the control. Well formed placenta was observed in 6% of the embryos treated with LIF and the most pronounced effect was recorded at 100 ng/ml. The data we obtained suggest that exogenous LIF can improve pre- and postimplantation development of parthenogenetic mouse embryos due, possibly, to increased survival rate of embryonic stem cells derived from the inner cell mass of blastocysts. LIF improves not only the development of the parthenogenetic embryo per se, but also the formation of its extraembryonic envelopes, which leads to the development of a larger placenta in LIF-treated parthenogenetic embryos, as compared to the control. 相似文献
19.
Ibragimova MI Petukhov VIu Zheglov EP Koniukhov GV Nizamov RN 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2004,44(5):524-528
The effect of radiotoxins (RT), obtained from gamma-irradiated potato tubers, on mice have been investigated using ex vivo EPR. Parts of liver, lung, spleen, heart and kidney were used for investigation. The amount of the preparations injected was 0.2 ml, RT concentration varying from 0.1 to 1 LD100 (LD100 = 100 mg/kg). An intraperitoneal injection of RT in dose of 0.1 LD100 resulted in metabolic changes only in spleen. During 8 hours after injection a gradual depression of enzyme ribonucleotide reductase activity in spleen has been observed. After the treatment of mice with a lethal dose of RT signals from nitrosyl complexes have been appeared in spectra from all tissue investigated. The intensities of lines depend both on a time passed after treatment and a sensitivity of tissue to RT action. One of the main reasons of the lethal outcome of mice treated with RT may be the breaking of the compensatory adaptive response due to enhanced hypoxic state resulting from the high concentration of nitrosyl complexes generated in the tissue. 相似文献
20.
This is a review of the data of clonal analysis of developing tissues in parthenogenetic and androgenetic chimeric mice. The time and causes of death of the parthenogenetic and androgenetic cell clones in chimeras are considered. The data obtained suggest that the development of cell clones, derivatives of the mesoderm and endoderm, is determined by the expression of alleles of the imprinted loci of paternal chromosomes, while the formation of cell clones, derivatives of the ectoderm, depends on the expression of other imprinted loci of maternal chromosomes. The death of androgenetic and parthenogenetic (gynogenetic) mammalian embryos is due to the lack of the expression of certain imprinted loci of the maternal and paternal genome, respectively. 相似文献