Medicine and Health Sciences Commons^™

An Injectable In Situ Forming Collagen/Alginate/Caso4 Composite Hydrogel For Tissue Engineering Applications: Optimization, Characterization And In Vitro Assessments, Samar A. Salim, Samar A. Salim

Nanotechnology Research Centre

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics …

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …

Development Of Rp-Hplc Method For Simultaneous Determination Of Nebivolol Hydrochloride, Valsartan And Hydrochlorothiazide In Co-Administrated Antihypertensive Agents And Human Plasma, Shereen Mowaka, M. Rizk, Maha M. Abou El‐Alamin, Mariam Mohamed

Pharmacy

Reversed phase high performance liquid chromatography combined with photodiode array (HPLC-PDA) detector method was developed for simultaneous determination of two binary antihypertensive combinations; either Nebivolol (NEB) with Hydrochlorothiazide (HCZ) or with Valsartan (VAL) in pharmaceutical formulation and spiked human plasma. The method was successfully applied to separate the three drugs on one chromatogram under the same chromatographic conditions that used for two binary combinations. The separation was established on Xterra C18 column using gradient mobile phase which composed of acidified water of pH = 3.0 (adjusted with 0.1% orthophosphoric acid) and acetonitrile with flow rate of 1.0 mL/min. The drugs …

Pyrazole-Sulfonamide Scaffold Featuring Dual-Tail Strategy As Apoptosis Inducers In Colon Cancer, Amira Khalil, Reham M. M. El Hazek, Nashwa H. Zaher, Hagar E. S. Emam, Marwa G. Elgazzar

Pharmacy

Dual-tail strategy has been successfully utilized in the development of novel carbonic anhydrase IX (CA IX) inhibitors. Herein we adopted this approach in the design and synthesis of a series of novel pyridine sulfonamide-pyrazole hybrid scaffold mimicking dual-tail inhibitors of CA IX. A library of 15 compounds was synthesized and assessed for their potential cytotoxic effects against colorectal cancer cells. Compounds 3, and 11 induced potential cytotoxic effects against the three cancer cell lines (HCT-116, HT-29, and SW-620) with IC₅₀s’ of 45.88, 28.27, and 16.57 uM, 25.01, 8.99, and 3.27 µM, respectively. Both compounds induced cellular apoptosis …

The Potential Off-Target Neuroprotective Effect Of Sister Gliflozins Suggests Their Repurposing Despite Not Crossing The Blood–Brain Barrier: From Bioanalytical Assay In Rats Into Theory Genesis, Shereen Mowaka, Moataz S. Hendy, Ehab F. Elkady, Asmaa El-Zaher, Bassam M. Ayoub

Pharmacy

Gliflozins are successfully marketed antidiabetic agents with a reported neuroprotective effect, and this study tests their blood–brain barrier crossing ability. Henceforward, a computational hypothesis interpreting their effects was reasonable after failure to cross into the brain. A chromatographic bioassay for canagliflozin, dapagliflozin, and empagliflozin was developed, validated, and applied to the rat's and rat's plasma and brain. HPLC method robustness was tested over two levels using Design of Experiment on MINITAB. It is the first method for gliflozins’ detection in rats’ brain tissue. The method was applied on 18 rats and six for each drug. Concentrations in plasma were determined …

Challenging Breast Cancer Through Novel Sulfonamide–Pyridine Hybrids: Design, Synthesis, Carbonic Anhydrase Ix Inhibition And Induction Of Apoptosis., Amira Khalil, Nashwa H. Zaher, Reham Mm Elhazek, Ahmed E. Gouda, Marwa G. Elgazzar

Pharmacy

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide–pyridine hybrids (2–12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC50 of compound 7 against carbonic anhydrase IX was 253 ± 12 nM using dorzolamide HCl as control. Conclusion: …

Characterization, Antibacterial, Antioxidant, Antidiabetic, And Anti-Inflammatory Activities Of Green Synthesized Silver Nanoparticles Using Phragmanthera Austroarabica A. G. Mill And J. A. Nyberg Extract, Shady Swidan, Dina Khodeer, Sarah Shabayek, Ali Nasr, Roaa Khinkar, Mohammed Aldurdunji, Maryam Ramadan, Jihan Badr

Pharmacy

Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.

Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.

Results …

Omarigliptin Attenuates Rotenone-Induced Parkinson's Disease In Rats: Possible Role Of Oxidative Stress, Endoplasmic Reticulum Stress And Immune Modulation, Shereen Mowaka, Haidy E. Michel, Mariam M. Tadros, Moataz S. Hendy, Bassam M. Ayoub

Pharmacy

The current study aimed to explore the potential neuroprotective effect of omarigliptin (OG), an antidiabetic drug that crosses the blood-brain barrier (BBB), in a Parkinson's disease (PD) rotenone-based rat-model. Results showed that OG attenuated motor impairment, histological aberrations, α-synuclein accumulation, and rescued the dopaminergic neurons in rotenone-administered rats. Furthermore, OG halted rotenone-induced oxidative stress; as shown by reduced lipid peroxidation, decline in the oxidative stress sensor (nuclear factor erythroid 2-related factor 2) and its downstream heme oxygenase-1. In addition, OG abrogated neuroinflammation and apoptosis in rotenone-treated rats. Moreover, OG ameliorated endoplasmic reticulum (ER) stress in rotenone-administered rats; as evidenced by …

Kinetic Degradation Study Of Ipragliflozin Coupled With Ms/Ms Structural Elucidation, Shereen Mowaka, Manar M. Elhassan,, Amr M. Mahmoud, Maha A. Hegazy

Pharmacy

Ipragliflozin degradation behavior was studied under different conditions: acidic, basic, photolytic, oxidative and thermal degradation conditions. This forced degradation study showed the extensive degradation of Ipragliflozin under acidic, basic and oxidative conditions while showed high stability under thermal and photo-degradation conditions. The separation of Ipragliflozin and its degradation products was done using Hypersil Gold® UPLC C18 column with 1.9 μm particle size (3 × 50 mm) as stationary phase and a mobile phase composed of acetonitrile: potassium monobasic phosphate buffer pH 3 (50:50; v/v) delivered at flow rate of 0.6 mL min−1. Validation of the proposed method was carried out …

Remdesivir Analog As Sars-Cov-2 Polymerase Inhibitor: Virtual Screening Of A Database Generated By Scaffold Replacement, Amgad Albohy, Mohamed A. Said, Mohamed A. Abdelrahman, Hany Said

Pharmacy

By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2. In this study, we used the interactions of the co-crystallized metabolite of remdesivir with SARS-CoV-2 RdRp isozyme (PDB 7BV2) to design an analog with potential …

In-Line Monitoring Of Sitagliptin Dissolution Profile From Tablets Utilizing An Eco-Friendly Potentiometric Sensor, Shereen Mowaka, Manar M. Elhassan, Amr M. Mahmoud, Maha A. Hegazy

Pharmacy

Sitagliptin, an oral antidiabetic drug, is an effective medication for lowering blood glucose level either as monotherapy or in combination with other antidiabetic drugs. This work aims for the fabrication of a potentiometric sensor for sitagliptin detection. The sensor was designed by doping the polyvinyl chloride polymeric ion-selective membrane with calix[4]arene as an ionophore which highly improved the linearity range (1 × 10−6—1 × 10−2 M), sensitivity, selectivity and limit of detection (6.3 × 10−7 M) compared to ionophore-free membrane. The method was then validated according to the International Council for Harmonization (ICH) guidelines. The sensor was successfully employed to …

Electrochemical Determination Of Ipragliflozin In Pure Form And In Spiked Human Plasma On A Glassy Carbon Electrode, Shereen Mowaka, Manar M. Elhassan, Amr M. Mahmoud, Maha A. Hegazy

Pharmacy

Ipragliflozin, a highly potent and selective sodium glucose cotransporter II inhibitor, is an effective blood glucose lowering drug in patients with type 2 diabetes mellitus by promoting urinary glucose excretion. The present work represents the first electrochemical determination of ipragliflozin that depends on the oxidation of sulfur atom present in its structure. Cyclic wave and differential pulse voltammetry were applied by scanning potential over range of 0 to 2.8 V vs the reference electrode Ag/Ag+ in non-aqueous medium. The method was developed and validated in accordance with the guidelines of the International Council for Harmonisation (ICH). With a detection limit …

'Induction Of Apoptosis, Cytotoxicity And Radiosensitization By Novel 3,4-Dihydroquinazolinone Derivatives, Eman Ramadan, Amira Khalil

Pharmacy

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC₅₀ in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC₅₀ values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in …

Sansevieria: An Evaluation Of Potential Cytotoxic Activity In Reference To Metabolomic And Molecular Docking Studies, Amgad Albohy

Pharmacy

Sansevieria trifasciata Prain. and Sansevieria suffruticosa N.E.Br. were selected to evaluate their cytotoxic activity against colon (CACO2), lung (A-549) and liver (HepG-2) carcinoma cell lines. Results indicated that S. suffruticosa N.E.Br. showed a significant cytotoxic effect on CACO2 with IC50= 30.9 ± 0.72 μg/ml. Evaluating the phenolic and flavonoid contents, S. suffruticosa N.E.Br. has higher total phenolic and flavonoid contents than S. trifasciata Prain. The phenolic content was estimated using HPLC detecting the presence of apigenin-7-glucoside and cinnamic acid only in S. suffruticosa N.E.Br. with p-hydroxybenzoic acid and p-coumaric acid being the major compounds. While, catechin and kaempferol are the …

Neuroprotective Repositioning And Anti-Tau Effect Of Carvedilol On Rotenone Induced Neurotoxicity In Rats: Insig& In Vivo Anti-Parkinson’S Disease Studyhts From An Insilico, Amgad Albohy, Rana Kamal, Esther Menze, Hebatalla I. Ahmed, Samar S. Azab

Pharmacy

Current treatments for Parkinson’s Disease (PD) only provide symptomatic relief; however, they don’t delay the disease progression, hence new treatment options should be considered. Carvedilol is a nonselective β & α1 blocker with additional effects as an antioxidant, anti-inflammatory and neuro protective properties. In this research, an insilico study was conducted to primarily evaluate carvedilol as an anti-parkinsonian and anti-tau protein target. PASS prediction was performed followed by a docking study of carvedilol. Carvedilol yielded promising results and forward guided this study onto its in vivo evaluation. The in vivo study aimed to assess the neuro-protective effects of carvedilol in …

Synthesis And Docking Studies Of A Novel Tetrahydroquinazoline Derivative As Promising Scaffold For Acetylcholine Esterase Inhibition, Amgad Albohy, Rawan A. , Alsuhaimat, Qais Abualassal, Zead Helmi Abudayeh, Sherif S. Ebada

Pharmacy

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders. While pathological hallmarks of this disorder are known, the exact cause of AD remains unclear. Quinazoline was found to be a promising scaffold for the design and development of Acetylcholinesterase (AChE) inhibitors. In this study, we report the synthesis of 1'-methyl-3',4'-dihydro1'Hspiro[ cyclopentane-1, 2'-quinazoline] (4) in 73.3% yield. The structure of compound 4 was confirmed with GC-MS, 1H and 13C-NMR. Acetylcholine esterase inhibition was studied virtually with docking into AChE active site and suggests potential use of 4 as a promising scaffold for acetylcholine esterase inhibitor design which might be …

Anabolic And Androgenic Effects Of Certain Atriplex Species Grown In Egypt, Dina M. El-Kersh, Fatma S. El-Sakhawy, Dina R. Abou-Hussein, Amany A. Sleem

Pharmacy

20-Hydroxyecdysone (20-HE) was detected by TLC in the ethyl acetate fraction of two Atriplex species grown in Egypt: A. lindleyi subsp. inflata and A. leucoclada. EIA quantification of 20-HE proved its presence in a concentration of 9.15 and 7.3 μg/g dried aerial parts in each of the two species, respectively. Significant anabolic and androgenic activities were demonstrated for 20-HE comparing to testosterone; the study also revealed that the total alcohol extract and the ethyl acetate fraction of A. lindleyi subsp. inflata exhibited greater activities than their analogues in A. leucoclada. Column chromatographic fractionation of the ethyl acetate fraction of the …