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981.
R. Padmini V. Uma Maheshwari P. Saravanan Keun Woo Lee M. Razia Mona S. Alwahibi B. Ravindran Mohamed Soliman Elshikh Young Ock Kim Hyungsuk Kim Hak-Jae Kim 《Saudi Journal of Biological Sciences》2020,27(12):3274-3289
Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC–MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5–2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC. 相似文献
982.
Mona M. Abdel-Atty Nahla A. Farag Rabah A. T. Serya Khaled A. M. Abouzid Samar Mowafy 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1290
A series of thieno[2,3-d]pyrimidine-based hydroxamic acid hybrids was designed and synthesised as multitarget anti-cancer agents, through incorporating the pharmacophore of EGFR, VEGFR2 into the inhibitory functionality of HDAC6. Three compounds (12c, 15b and 20b) were promising hits, whereas (12c) exhibited potent VEGFR2 inhibition (IC50=185 nM), potent EGFR inhibition (IC50=1.14 µM), and mild HDAC6 inhibition (23% inhibition). Moreover, compound (15c) was the most potent dual inhibitor among all the synthesised compounds, as it exhibited potent EGFR and VEGFR2 inhibition (IC50=19 nM) and (IC50=5.58 µM), respectively. While compounds (20d) and (7c) displayed nanomolar selective kinase inhibition with EGFR IC50= 68 nM and VEGFR2 IC50= 191 nM, respectively. All of the synthesised compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumour cell lines. Additionally, molecular docking studies and ADMET studies were carried out to gain further insight into their binding mode and predict the pharmacokinetic properties of all the synthesised inhibitors. 相似文献
983.
Alessandro Deplano Jessica Karlsson Federica Moraca Mona Svensson Claudia Cristiano Carmine Marco Morgillo Christopher J. Fowler Roberto Russo Bruno Catalanotti Valentina Onnis 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):940
Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1''-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds. 相似文献
984.
Saqib Bashir Muhammad Abdul Qayyum Arif Husain Ali Bakhsh Niaz Ahmed Muhammad Baqir Hussain Mohamed Soliman Elshikh Mona S. Alwahibi Bandar M.A. Almunqedhi Riaz Hussain Yong-Feng Wang Yi Zhou Zeng-Hui Diao 《Saudi Journal of Biological Sciences》2021,28(4):2453-2459
Cadmium contamination in croplands is recognized one of the major threat, seriously affecting soil health and sustainable agriculture around the globe. Cd mobility in wastewater irrigated soils can be curtailed through eco-friendly and cost effective organic soil amendments (biochars) that eventually minimizes its translocation from soil to plant. This study explored the possible effects of various types of plants straw biochar as soil amendments on cadmium (Cd) phytoavailability in wastewater degraded soil and its subsequent accumulation in sunflower tissues. The studied biochars including rice straw (RS), wheat straw (WS), acacia (AC) and sugarcane bagasse (SB) to wastewater irrigated soil containing Cd. Sunflower plant was grown as a test plant and Cd accumulation was recorded in its tissues, antioxidant enzymatic activity chlorophyll contents, plant biomass, yield and soil properties (pH, NPK, OM and Soluble Cd) were also examined. Results revealed that addition of biochar significantly minimized Cd mobility in soil by 53.4%, 44%, 41% and 36% when RS, WS, AC and SB were added at 2% over control. Comparing the control soil, biochar amended soil effectively reduced Cd uptake via plants shoots by 71.7%, 60.6%, 59% and 36.6%, when RS, WS, AC and SB. Among all the biochar, rice husk induced biochar significantly reduced oxidative stress and reduced SOD, POD and CAT activity by 49%, 40.5% and 46.5% respectively over control. In addition, NPK were significantly increased among all the added biochars in soil–plant system as well as improved chlorophyll contents relative to non-bioachar amended soil. Thus, among all the amendments, rice husk and wheat straw biochar performed well and might be considered the suitable approach for sunflower growth in polluted soil. 相似文献
985.
Akmal A. Sakr Mohamed F. Ghaly H. G. M. Edwards Mona F. Ali 《Geomicrobiology journal》2020,37(7):653-662
AbstractStreptomyces are involved in the deterioration of cultural heritage materials through several pathways, the most important of these are biomineralization and bio-pigment production. The biomineralization pathway can occur through the precipitation of calcite, silica, barytes, hydromagnesite and iron compounds on colonized paintings and on stone surfaces with paintings in relief. Streptomyces biomineralize boron although it was confirmed in biodeterioration of cultural heritage materials. The other pathway occurs via bio pigment production and the most common of these biopigments are melanin with colors ranging from black through brown to olive, carotenoids with colors ranging from red, yellow, and pink through to violet and thirdly, actinorhodin-related blue pigments. 相似文献
986.
Anton V. Persikov Joshua L. Wetzel Elizabeth F. Rowland Benjamin L. Oakes Denise J. Xu Mona Singh Marcus B. Noyes 《Nucleic acids research》2015,43(3):1965-1984
Cys2His2 zinc fingers (C2H2-ZFs) comprise the largest class of metazoan DNA-binding domains. Despite this domain''s well-defined DNA-recognition interface, and its successful use in the design of chimeric proteins capable of targeting genomic regions of interest, much remains unknown about its DNA-binding landscape. To help bridge this gap in fundamental knowledge and to provide a resource for design-oriented applications, we screened large synthetic protein libraries to select binding C2H2-ZF domains for each possible three base pair target. The resulting data consist of >160 000 unique domain–DNA interactions and comprise the most comprehensive investigation of C2H2-ZF DNA-binding interactions to date. An integrated analysis of these independent screens yielded DNA-binding profiles for tens of thousands of domains and led to the successful design and prediction of C2H2-ZF DNA-binding specificities. Computational analyses uncovered important aspects of C2H2-ZF domain–DNA interactions, including the roles of within-finger context and domain position on base recognition. We observed the existence of numerous distinct binding strategies for each possible three base pair target and an apparent balance between affinity and specificity of binding. In sum, our comprehensive data help elucidate the complex binding landscape of C2H2-ZF domains and provide a foundation for efforts to determine, predict and engineer their DNA-binding specificities. 相似文献
987.
Rasha AH Attia Abeer E Mahmoud Haiam Mohammed Mahmoud Farrag Rania Makboul Mona Embarek Mohamed Zedan Ibraheim 《Memórias do Instituto Oswaldo Cruz》2015,110(8):1035-1041
Trichinellosis is a serious disease with no satisfactory treatment. We aimed to
assess the effect of myrrh (Commiphora molmol) and, for the first
time, thyme (Thymus vulgaris L.) against enteral
and encysted (parenteral) phases of Trichinella spiralis in mice
compared with albendazole, and detect their effect on inducible nitric oxide synthase
(iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult
reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%),
respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae
reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating
intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated
mice showed the highest iNOS expression followed by albendazole, then thyme. On the
other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of
inflammatory cells infiltrating and surrounding encapsulated T.
spiralis larvae than albendazole treated group. In conclusion, myrrh and
thyme extracts are highly effective against both phases of T.
spiralis and showed strong iNOS expressions, especially myrrh which could
be a promising alternative drug. This experiment provides a basis for further
exploration of this plant by isolation and retesting the active principles of both
extracts against different stages of T. spiralis. 相似文献
988.
989.
990.
Pourakbari B Mirsalehian A Maleknejad P Mamishi S Azhdarkosh H Daryani NE Najafi M Kazemi B Paknejad M Mahmoudi S Bandehpour M Ghazi M Salavati A 《Helicobacter》2011,16(1):42-46
Background: Nowadays, there is an increasing interest in noninvasive methods to diagnose Helicobacter pylori infection. Indeed, they can profitably replace endoscopy in predicting the diagnosis. The stool antigen test for H. pylori is a noninvasive immunoassay to diagnose active infection with this bacterium in human fecal samples. The aim of this study was detection of alkyl hydroperoxide reductase protein (AhpC) antigen by immunoblotting in stool samples for diagnosis of H. pylori. Materials and Methods: Chromosomal DNA from H. pylori was isolated. AhpC gene was amplified by PCR, These amplicons were cloned into pTZ57R/T cloning vector then subcloned into pQE30 expression vector and overexpressed using isopropyl‐beta‐D‐thiogalactopyranoside in E. coli M15. AhpC protein was purified by affinity chromatography. Rabbits were immunized with the purified AhpC protein for the production of antibodies. To determine the accuracy of the test for diagnosing H. pylori infection from stool, we evaluated 84 patients (6–81 years old) using Western blot analysis by rabbit anti‐AhpC antibody. Positive rapid urease test on biopsy samples was considered as the gold standard. Results: AhpC gene was overexpressed, and AhpC protein was purified. Rabbit anti‐AhpC antibody produced after immunization with the purified AhpC protein. By immunoblotting, we detected AhpC protein in the positive stool samples. The test showed a 83.3% sensitivity (95% CI: 69.8–92.5%) and a 91.7% specificity (95% CI: 77.5–98.2). Among the children, the sensitivity was 88.2% (95% CI: 63.6–98.5) and the specificity was 100% (95% CI: 69.2–100); in adults, the sensitivity and specificity were 80.6% (95% CI: 62.5–92.5) and 88.5% (95% CI: 69.8–97.6), respectively. Conclusions: Using of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children, and can be used for the development of a stool antigen detection kit for H. pylori. 相似文献