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101.
Ziad Omran Chris P. Guise Linwei Chen Cyril Rauch Ashraf N. Abdalla Omeima Abdullah Ikhlas A. Sindi Peter M. Fischer Jeff B. Smaill Adam V. Patterson Yuxiu Liu Qingmin Wang 《Molecules (Basel, Switzerland)》2021,26(11)
Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions. 相似文献
102.
Safialdin Alsanosi Ryan A. Sheikh Sultan Sonbul Hisham N. Altayb Afnan S. Batubara Salman Hosawi Kaltoom Al-Sakkaf Omeima Abdullah Ziad Omran Mahmoud Alhosin 《Molecules (Basel, Switzerland)》2022,27(9)
Nigella sativa oil, commonly known as black seed oil (BSO), is a well-known Mediterranean food, and its consumption is associated with beneficial effects on human health. A large number of BSO’s therapeutic properties is attributed to its pharmacologically active compound, thymoquinone (TQ), which inhibits cell proliferation and induces apoptosis by targeting several epigenetic players, including the ubiquitin-like, containing plant homeodomain (PHD) and an interesting new gene, RING finger domains 1 (UHRF1), and its partners, DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1). This study was designed to compare the effects of locally sourced BSO with those of pure TQ on the expression of the epigenetic complex UHRF1/DNMT1/HDAC1 and the related events in several cancer cells. The gas chromatographs obtained from GC-MS analyses of extracted BSO showed that TQ was the major volatile compound. BSO significantly inhibited the proliferation of MCF-7, HeLa and Jurkat cells in a dose-dependent manner, and it induced apoptosis in these cell lines. BSO-induced inhibitory effects were associated with a significant decrease in mRNA expression of UHRF1, DNMT1 and HDAC1. Molecular docking and MD simulation showed that TQ had good binding affinity to UHRF1 and HDAC1. Of note, TQ formed a stable metal coordinate bond with zinc tom, found in the active site of the HDAC1 protein. These findings suggest that the use of TQ-rich BSO represents a promising strategy for epigenetic therapy for both solid and blood tumors through direct targeting of the trimeric epigenetic complex UHRF1/DNMT1/ HDAC1. 相似文献
103.
Synthesis and Reactivity of Enaminones: Synthesis of Some 1,3,4‐Thiadiazole Linked to Pyrazole,Pyridine, Benzimidazolopyrimidine,Pyrazolopyrimidine, Pyrazolotriazine and Triazolotriazine Derivatives 下载免费PDF全文
1,3,4‐Thiadiazole‐enaminone ( 6 ) was synthesized via reaction of the benzamide ( 5 ) with DMF‐DMA. The simple thiadiazole‐enaminone ( 6 ) was used as a synthetic precursor for the synthesis of a wide variety of new heterocyclic compounds, including the 5‐substituted‐1,3,4‐thiadiazole derivatives ( 7 ), ( 8 ), ( 16 ), ( 17 ) and ( 18 ), which were obtained via reactions of ( 6 ) with nitrogen nucleophiles. Also, reactions of enaminone ( 6 ) with carbon nucleophiles afforded the respective 1,3,4‐thiadiazoles ( 10a , 10b ). Diazotization of the benzamide ( 20 ) with the heteroaromatic amine salts gave the hydrazone derivatives ( 21 ) and ( 22 ). Cyclization of the latter hydrazones yielded the corresponding pyrazolotriazine and 1,2,4‐triazolotriazine derivatives ( 23 ) and ( 24 ), respectively. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. 相似文献
104.
Aladdin Riad Sarah B. Gitto Hwan Lee Harrison D. Winters Paul M. Martorano Chia-Ju Hsieh Kuiying Xu Dalia K. Omran Daniel J. Powell Jr. Robert H. Mach Mehran Makvandi 《Molecules (Basel, Switzerland)》2020,25(24)
Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. Here, we investigated a radioiodinated PARP inhibitor, [125I]KX1, and show drug target specific DNA damage and subsequent killing of BRCA1 and non-BRCA mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. Furthermore, we demonstrated that viable tumor tissue from ovarian cancer patients can be used to screen tumor radiosensitivity ex-vivo, enabling the direct assessment of therapeutic efficacy. Finally, we showed tumors can be imaged by single-photon computed tomography (SPECT) with PARP theranostic, [123I]KX1, in a human ovarian cancer xenograft mouse model. These data support the utility of PARP-1 targeted radiopharmaceutical therapy as a theranostic option for PARP-1 overexpressing ovarian cancers. 相似文献
105.
Johnson SA Doster ME Matthews J Shoshani M Thibodeau M Labadie A Hatnean JA 《Dalton transactions (Cambridge, England : 2003)》2012,41(26):8135-8143
The complex ((i)Pr(3)P)Ni(η(2)-Bu(3)SnCH=CH(2))(2) (1a) was characterized by NMR spectroscopy and was identified as the active species for catalytic C-H bond stannylation of partially fluorinated aromatics, for example in the reaction between pentafluorobenzene and Bu(3)SnCH=CH(2), which generates C(6)F(5)SnBu(3) and ethylene. The crystalline complex ((i)Pr(3)P)Ni(η(2)-Ph(3)SnCH=CH(2))(2) (1b) provides a more easily handled analogue, and is also capable of catalytic stannylation with added Ph(3)SnCH=CH(2) and C(6)F(5)H. Mechanistic studies on 1b show that the catalytically active species remains mononuclear. The rate of catalytic stannylation is proportional to [C(6)F(5)H] and inversely proportional to [Ph(3)SnCH=CH(2)]. This is consistent with a mechanism where reversible Ph(3)SnCH=CH(2) dissociation provides ((i)Pr(3)P)Ni(η(2)-Ph(3)SnCH=CH(2)), followed by a rate-determining reaction with C(6)F(5)H to generate the stannylation products. Kinetic competition reactions between the fluorinated aromatics pentafluorobenzene, 1,2,4,5-tetrafluorobenzene, 1,2,3,5-tetrafluorobenzene, 1,2,4-trifluorobenzene, 1,3,5-trifluorobenzene and 1,3-difluorobenzene all suggest significant Ni-aryl bond formation in the rate-determining step under catalytic conditions. Labelling studies are consistent with an insertion of the hydrogen of the arene into the vinyl group, followed by β-elimination or β-abstraction of the SnPh(3) moiety. 相似文献
106.
107.
Jilan A. Nazeam Hala M. El-Hefnawy Gamal Omran Abdel-Naser Singab 《Natural product research》2018,32(12):1484-1488
Hypolipidemic effect of Portulaca oleracea L. seed extract and its fractions have been studied on streptozotocin (STZ) at dose 75 mg/kg b.wt. After fractionation of the alcoholic extract; petroleum ether fraction was the most active fraction that decreased different hyperlipidemia biochemical parameters. After chromatographic analysis; oleamide, ethylpalmitate, β-amyrin, stigmasterol and β-sitosterol were identified. The GLC analysis of unsaponifiable matter revealed the presence of; lignoceric acid as a major constituent in the most bioactive fraction. In conclusion, petroleum ether fraction possessed a hypolipidemic effect in STZ-induced diabetic rats, which may be attributed to its phytosterols, fatty acid and amide compounds. The finding of the present investigation strongly demonstrates the potential of non-polar fraction of P. oleracea L. seed in combating hyperlipidemia in diabetic condition. So the petroleum ether fractions and its constituents can be used as hypolipdemic supplement in the developing countries towards the development of new therapeutic agents. 相似文献
108.
Ahmed Omran Alhareb Hazizan Md Akil Zainal Arifin Ahmad 《Journal of Thermal Analysis and Calorimetry》2018,134(2):941-951
This study is to investigate the effect of nitrile butadiene rubber (NBR as impact modifier) together with Al2O3/YSZ (toughening) as filler loading in PMMA denture base on the thermal and mechanical properties. PMMA matrix without fillers was mixed between PMMA powder and 0.5 mass% of BPO, and it is used as the control group. The liquid components consist of 90% of methyl methacrylate (MMA) and 10% as the cross-linking agent of ethylene glycol dimethacrylate. The denture base composites were fabricated by incorporating PMMA powder and BPO and fixed at 7.5 mass% NBR particles and filler loading (1, 3, 5, 7 and 10 mass%) of Al2O3/YSZ mixture filler by (1:1 ratio) as the powder components. The ceramic fillers were treated with silane (γ-MPS) and the powder/liquid ratio (P/L) according to dental laboratory practice. The TGA data obtained show that the PMMA composites have better thermal stability compared to unreinforced PMMA, while DSC curves show slightly similar Tg values. DSC results also indicated the presence of unreacted monomer content for both reinforced and unreinforced PMMA composites. The fracture toughness, Vickers hardness and flexural modulus values were statistically increased compared to the unreinforced PMMA matrix (P?<?0.05). 相似文献
109.
A library of one of the two Lyme disease antigens, BbGL1, has been synthesized in four steps from d-galactose using BF(3)-promoted glycosylation of the peracetate to introduce the cholesteryl β-glycoside and TBTU-promoted esterification to add a range of fatty acids regioselectively at O-6 of d-galactose in good yield. 相似文献
110.
A new, specific, and sensitive RP-HPLC method was developed for the simultaneous determination of eprosartan (EPR) and hydrochlorothiazide (HCT). Good chromatographic separation was achieved using a 250 x 4.6 mm id, 5 microm particle size Symmetry C18 column. The mobile phase acetonitrile-0.1 M phosphate buffer (35+65, v/v), pH 4.5, was pumped at a flow rate of 1 mL/min, with UV detection at 275 nm. The method showed good linearity in the ranges of 0.5-50 and 0.1-10 microg/mL, with LOD of 0.06 and 0.02 microg/mL and LOQ of 0.20 and 0.08 microg/mL for EPR and HCT, respectively. The proposed method was successfully applied for the analysis of the studied drugs in their synthetic mixture and co-formulated tablets. The method was further extended to the in vitro and in vivo determination of the two drugs in spiked and real human plasma. Interference likely to be encountered from the co-administered drugs was studied. 相似文献