Hassan A

References (15)

Title : Unleashing new MTDL AChE and BuChE inhibitors as potential anti-AD therapeutic agents: In vitro, in vivo and in silico studies - Zaafar_2024_Int.J.Biol.Macromol__131740
Author(s) : Zaafar D , Elghazawy NH , Hassan A , Mahmoud MY , Bakr AF , Arafa RK
Ref : Int J Biol Macromol , :131740 , 2024
Abstract : Alzheimer's disease (AD) is challenging due to its irreversible declining cognitive symptoms and multifactorial nature. This work tackles targeting both acetylcholinesterase (AChE) and BuChE with a multitarget-directed ligand (MTDL) through design, synthesis, and biological and in silico evaluation of a series of twenty eight new 5-substituted-2-anilino-1,3,4-oxadiazole derivatives 4a-g, 5a-g, 9a-g and 13a-g dual inhibitors of the target biomolecules. In vitro cholinesterases inhibition and selectivity assay of the synthesized derivatives showed excellent nanomolar level inhibitory activities. Compound 5a, the most potent inhibitor, elicited IC(50)s of 46.9 and 3.5 nM against AChE and BuChE, respectively (SI = 0.07), 5 folds better than the known dual inhibitor Rivastagmine. In vivo and ex vivo investigation showed that 5a significantly inhibited MDA levels and increased GSH contents, thus, attenuating the brain tissue oxidative stress. Additionally, 5a significantly decreased AChE and BuChE levels and inhibited self-mediated beta-amyloid aggregation in brains of treated rats. Histopathological and immunohistochemical evaluation demonstrated lessened damage and decreased caspase-3 and VEGF expression levels. In silico prediction of 5a's pharmacokinetics and toxicity profiles reflected promising results. Finally, 5a demonstrated tight binding interactions with the two target biomolecules upon docking along with stable complex formation with its bio-targets throughout the 100 ns MD trajectories.
ESTHER : Zaafar_2024_Int.J.Biol.Macromol__131740
PubMedSearch : Zaafar_2024_Int.J.Biol.Macromol__131740
PubMedID: 38653428

Title : Effect of entomopathogenic fungi on behavior and physiology of Solenopsis invicta (Hymenoptera, Formicidae) - Hassan_2024_J.Econ.Entomol__
Author(s) : Hassan A , Kang L , Zhang K , Wang L , Qin X , Fang G , Lu Y , Huang Q
Ref : J Econ Entomol , : , 2024
Abstract : In an ant colony, a large number of nestmates with a similar gene pool coexist, making them more vulnerable to pathogenic attacks. These pathogens influence the behavior and physiology of the fire ant Solenopsis invicta Buren. Here, we evaluated the impact of entomopathogenic fungi (EPF) Metarhizium anisopliae on the behavior (locomotion and foraging) and physiology (biological molecules, anti-fungal activity, and survival) of S. invicta. Distance traveled and velocity significantly decreased, while turn angle and angular velocity significantly increased in ants exposed to a higher concentration of M. anisopliae compared to ants exposed to control after 36 h, which showed disturbed locomotion. Fungus infection significantly affected the foraging behavior of ants. Fungus-exposed ants spent significantly less time in the food zone (area with food) than in the inner zone (area without food). The activities of 4 enzymes, peroxidase, glutathione-S-transferase, hydrogen peroxide (H2O2), and carboxylesterase were significantly decreased. In contrast, catalase and anti-fungal activities were increased after fungal exposure compared to the control. The activity of acetylcholinesterase, which hydrolyses the important neurotransmitter acetylcholine, also decreased after fungal application compared to the control. Survival of ants was also significantly reduced after fungus infection compared to the control. Our findings help to understand the influence of M. anisopliae on the behavior and physiology of S. invicta, which will help in the management of S. invicta using the EPF M. anisopliae.
ESTHER : Hassan_2024_J.Econ.Entomol__
PubMedSearch : Hassan_2024_J.Econ.Entomol__
PubMedID: 38634604

Title : Exploring fluorine-substituted piperidines as potential therapeutics for diabetes mellitus and Alzheimer's diseases - Mughal_2024_Eur.J.Med.Chem_273_116523
Author(s) : Mughal EU , Hawsawi MB , Naeem N , Hassan A , Alluhaibi MS , Ali Shah SW , Nazir Y , Sadiq A , Alrafai HA , Ahmed SA
Ref : Eur Journal of Medicinal Chemistry , 273 :116523 , 2024
Abstract : In the current study, a series of fluorine-substituted piperidine derivatives (1-8) has been synthesized and characterized by various spectroscopic techniques. In vitro and in vivo enzyme inhibitory studies were conducted to elucidate the efficacy of these compounds, shedding light on their potential therapeutic applications. To the best of our knowledge, for the first time, these heterocyclic structures have been investigated against alpha-glucosidase and cholinesterase enzymes. The antioxidant activity of the synthesized compounds was also assessed. Evaluation of synthesized compounds revealed notable inhibitory effects on alpha-glucosidase and cholinesterases. Remarkably, the target compounds (1-8) exhibited extraordinary alpha-glucosidase inhibitory activity as compared to the standard acarbose by several-fold. Subsequently, the potential antidiabetic effects of compounds 2, 4, 5, and 6 were validated using a STZ-induced diabetic rat model. Kinetic studies were also performed to understand the mechanism of inhibition, while structure-activity relationship analyses provided valuable insights into the structural features governing enzyme inhibition. Kinetic investigations revealed that compound 4 displayed a competitive mode of inhibition against alpha-glucosidase, whereas compound 2 demonstrated mixed-type behavior against AChE. To delve deeper into the binding interactions between the synthesized compounds and their respective enzyme targets, molecular docking studies were conducted. Overall, our findings highlight the promising potential of these densely substituted piperidines as multifunctional agents for the treatment of diseases associated with dysregulated glucose metabolism and cholinergic dysfunction.
ESTHER : Mughal_2024_Eur.J.Med.Chem_273_116523
PubMedSearch : Mughal_2024_Eur.J.Med.Chem_273_116523
PubMedID: 38795518

Title : Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke - Yu_2023_J.Am.Heart.Assoc_12_e026901
Author(s) : Yu D , Liang N , Zebarth J , Shen Q , Ozzoude M , Goubran M , Rabin JS , Ramirez J , Scott CJM , Gao F , Bartha R , Symons S , Haddad SMH , Berezuk C , Tan B , Kwan D , Hegele RA , Dilliott AA , Nanayakkara ND , Binns MA , Beaton D , Arnott SR , Lawrence-Dewar JM , Hassan A , Dowlatshahi D , Mandzia J , Sahlas D , Casaubon L , Saposnik G , Otoki Y , Lanctot KL , Masellis M , Black SE , Swartz RH , Taha AY , Swardfager W
Ref : J Am Heart Assoc , 12 :e026901 , 2023
Abstract : Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME]sand 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME]sand 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imagingscriteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared withsparticipants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (beta=0.251, P=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (beta=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (beta=0.364, P<0.001; beta=0.362, P<0.001) and white matter MRI-visible perivascular spaces (beta=0.302, P=0.011; beta=0.314, P=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (beta=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (beta=-0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
ESTHER : Yu_2023_J.Am.Heart.Assoc_12_e026901
PubMedSearch : Yu_2023_J.Am.Heart.Assoc_12_e026901
PubMedID: 36583428

Title : Evaluation of gene expression of PLEKHS1, AADAC, and CDKN3 as novel genomic markers in gastric carcinoma - Abdel-Tawab_2022_PLoS.One_17_e0265184
Author(s) : Abdel-Tawab MS , Fouad H , Othman AM , Eid RA , Mohammed MA , Hassan A , Reyad HR
Ref : PLoS ONE , 17 :e0265184 , 2022
Abstract : Gastric cancer (GC) is considered lethal aggressive cancer. In Egypt, GC has a low incidence but unfortunately, it is mostly diagnosed at an advanced stage with a poor prognosis. Assessment of novel markers that can be used in the early detection of GC is an urgent need. The present study was performed to assess the association of the Pleckstrin homology domain-containing S1 (PLEKHS1) arylacetamide deacetylase (AADAC, and Cyclin-dependent kinase inhibitor 3 (CDKN3) genes with GC and to correlate their gene expression levels with tumor stage, grade, and other clinicopathological features. The current work was performed on forty gastric tissue samples; twenty in Group 1 with GC tissues at different stages, and grades and twenty in Group 2 (control group) with non-tumorous tissue. PLEKHS1, AADAC, and CDKN3 gene expression were assessed by RT-qPCR. AADAC, CDKN3 genes were significantly (p<0.001) upregulated, while PLEKHS1 gene was significantly (p<0.001) downregulated in the GC group than the control group. AADAC gene expression exhibited a high significant (p<0.001) positive correlation with the tumor grades and the tumor stages. A high significant negative correlation between AADAC, and CDKN3 gene expression (r = -.760, p<0.001) was found. The three studied parameters showed high significant sensitivity and specificity in the prediction of the presence of GC. PLEKHS1, AADAC, and CDKN3 gene expressions were suggested to be used as diagnostic and predictive biomarkers of GC, additionally, AADAC may be used as a prognostic marker in these patients for further future confirming studies.
ESTHER : Abdel-Tawab_2022_PLoS.One_17_e0265184
PubMedSearch : Abdel-Tawab_2022_PLoS.One_17_e0265184
PubMedID: 35446856

Title : Neuroprotective effects of Bhilawanol and Anacardic acid during glutamate-induced neurotoxicity - Al Mughairbi_2021_Saudi.Pharm.J_29_1043
Author(s) : Al Mughairbi F , Nawaz R , Khan F , Hassan A , Mahmood N , Ahmed HT , Alshamali A , Ahmed S , Bashir A
Ref : Saudi Pharm J , 29 :1043 , 2021
Abstract : Bhilawanol (Bh) and anacardic acid (AA) are two lipid-soluble compounds mostly found in the nut of Semecarpus anacardium (SA). This herb has many medicinal properties including enhancing learning and memory, yet its active compounds have not been studied for neuroprotective effects. We investigated the neuroprotective effects of Bh and AA against glutamate induced cell death in the adrenal pheochromocytoma cell line of rats (PC12 cells). Cell viability, toxicity and calcium influx were determined by MTT assay, LDH release assay and Fluo-3 imaging while apoptosis was assayed by caspase-3 and Bcl-2 gene expression. Our results showed that Bh and AA treatments significantly increased cell viability, reduced cell toxicity and calcium influx in PC12 cells in addition to suppressing the reactive oxygen species. Furthermore, AA treatment decreased caspase-3 expression level whereas both Bh and AA enhanced the expression of anti-apoptotic gene Bcl-2 in PC12 cells. Both compounds potently inhibited acetylcholinesterase enzyme (AChE) in a dose and time dependent manner. These findings suggest that the traditional use of SA may be explained on the basis of both Bh and AA showing neuroprotective potential due to their effects on enhancing cell viability, reducing cell toxicity most probably by reducing excessive calcium influx and suppression of ROS as well as by decreasing the expression of proapoptotic caspase 3 gene and increasing the expression of antiapoptotic gene Bcl2. Traditional use in enhancing learning and memory was justified in part by inhibition of AChE.
ESTHER : Al Mughairbi_2021_Saudi.Pharm.J_29_1043
PubMedSearch : Al Mughairbi_2021_Saudi.Pharm.J_29_1043
PubMedID: 34588850

Title : Design, synthesis and bioevaluation of tricyclic fused ring system as dual binding site acetylcholinesterase inhibitors - Tanoli_2018_Bioorg.Chem_83_336
Author(s) : Tanoli ST , Ramzan M , Hassan A , Sadiq A , Jan MS , Khan FA , Ullah F , Ahmad H , Bibi M , Mahmood T , Rashid U
Ref : Bioorg Chem , 83 :336 , 2018
Abstract : Due to recently discovered non-classical acetylcholinesterase (AChE) function, dual binding-site AChE inhibitors have acquired a paramount attention of drug designing researchers. The unique structural arrangements of AChE peripheral anionic site (PAS) and catalytic site (CAS) joined by a narrow gorge, prompted us to design the inhibitors that can interact with dual binding sites of AChE. Eighteen homo- and heterodimers of desloratadine and carbazole (already available tricyclic building blocks) were synthesized and tested for their inhibition potential against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBChE). We identified a six-carbon tether heterodimer of desloratadine and indanedione based tricyclic dihydropyrimidine (4c) as potent and selective inhibitor of eeAChE with IC50 value of 0.09+/-0.003muM and 1.04+/-0.08muM (for eqBChE) with selectivity index of 11.1. Binding pose analysis of potent inhibitors suggest that tricyclic ring is well accommodated into the AChE active site through hydrophobic interactions with Trp84 and Trp279. The indanone ring of most active heterodimer 4b is stabilized into the bottom of the gorge and forms hydrogen bonding interactions with the important catalytic triad residue Ser200.
ESTHER : Tanoli_2018_Bioorg.Chem_83_336
PubMedSearch : Tanoli_2018_Bioorg.Chem_83_336
PubMedID: 30399465

Title : Modification of Bischler-Mohlau indole derivatives through palladium catalyzed Suzuki reaction as effective cholinesterase inhibitors, their kinetic and molecular docking studies - Parveen_2017_Bioorg.Chem_76_166
Author(s) : Parveen S , Shah MS , Zaib S , Gul T , Khan KM , Iqbal J , Hassan A
Ref : Bioorg Chem , 76 :166 , 2017
Abstract : Due to the immense importance of aryl indole nucleus, herein we report the palladium-catalyzed arylation of N-substituted 2-aryl indole utilizing Suzuki-Miyaura cross coupling methodology. The biological screening for cholinesterase inhibition of the resulted biaryl indole moieties was carried out to evaluate their pharmacological potential, expecting to involve the development of new therapeutics for various inflammatory, cardiovascular, gastrointestinal and neurological diseases. This research work also involved the use of utilization of microwave-assisted organic synthesis (MAOS) for the synthesis of Bischler-Mohlau indole which is further biarylated via palladium-catalyzed cross coupling reaction. All the synthetic compounds (3a-n) were tested for cholinesterase inhibition and exhibited high level of AChE inhibitory activities. Interestingly, compounds 3m and 3n were found to be dual inhibitors, however, remaining compound exhibited no inhibitory activity against BChE. The biological potential of the resulted compounds was explained on the basis of molecular docking studies, performed against AChE and BChE, exploring the probable binding modes of most potent inhibitors.
ESTHER : Parveen_2017_Bioorg.Chem_76_166
PubMedSearch : Parveen_2017_Bioorg.Chem_76_166
PubMedID: 29175588

Title : Potential Role of Honey in Learning and Memory - Othman_2015_Med.Sci.(Basel)_3_3
Author(s) : Othman Z , Zakaria R , Hussain NHN , Hassan A , Shafin N , Al-Rahbi B , Ahmad AH
Ref : Med Sci (Basel) , 3 :3 , 2015
Abstract : The composition and physicochemical properties of honey are variable depending on its floral source and often named according to the geographical location. The potential medicinal benefits of Tualang honey, a multifloral jungle honey found in Malaysia, have recently been attracting attention because of its reported beneficial effects in various diseases. This paper reviews the effects of honey, particularly Tualang honey, on learning and memory. Information regarding the effects of Tualang honey on learning and memory in human as well as animal models is gleaned to hypothesize its underlying mechanisms. These studies show that Tualang honey improves morphology of memory-related brain areas, reduces brain oxidative stress, increases brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) concentrations, and reduces acetylcholinesterase (AChE) in the brain homogenates. Its anti-inflammatory roles in reducing inflammatory trigger and microglial activation have yet to be investigated. It is hypothesized that the improvement in learning and memory following Tualang honey supplementation is due to the significant improvement in brain morphology and enhancement of brain cholinergic system secondary to reduction in brain oxidative damage and/or upregulation of BDNF concentration. Further studies are imperative to elucidate the molecular mechanism of actions.
ESTHER : Othman_2015_Med.Sci.(Basel)_3_3
PubMedSearch : Othman_2015_Med.Sci.(Basel)_3_3
PubMedID: 29083387

Title : Additive effects of a cholinesterase inhibitor and a histamine inverse agonist on scopolamine deficits in humans - Cho_2011_Psychopharmacology.(Berl)_218_513
Author(s) : Cho W , Maruff P , Connell J , Gargano C , Calder N , Doran S , Fox-Bosetti S , Hassan A , Renger J , Herman G , Lines C , Verma A
Ref : Psychopharmacology (Berl) , 218 :513 , 2011
Abstract : RATIONALE: Enhancement of histaminergic neurotransmission or histaminergic plus cholinergic neurotransmission may represent novel strategies for improving cognition in Alzheimer's disease. OBJECTIVE: To evaluate the effects of a novel histamine H3 receptor inverse agonist (MK-3134), an acetylcholinesterase inhibitor (donepezil), and their combination in attenuating the cognitive impairment associated with scopolamine. METHODS: Thirty-one subjects were randomized, and 28 completed this double-blind, placebo-controlled, five-period crossover study. Cognition was assessed using the Groton Maze Learning Task (GMLT) as the primary outcome measure. The two primary hypotheses were that donepezil 10 mg and MK-3134 25 mg, respectively, would attenuate scopolamine (0.5 mg)-induced impairment as measured by the GMLT over the first 12 h after scopolamine administration (AUC(1-12) (h)). A secondary hypothesis was that the combination of donepezil and MK-3134 would attenuate scopolamine-induced cognitive impairment to a greater extent than either agent alone as measured by the GMLT AUC(1-12 h). RESULTS: The primary and secondary hypotheses were not met. Upon examining the time course of the scopolamine effects (an exploratory objective), peak effects were generally observed around 2 h after scopolamine administration. Administration of MK-3134 or donepezil improved performance on the GMLT at the 2-h time point, rather than AUC(1-12 h), compared with scopolamine alone. Moreover, it appeared that the combination of MK-3134 and donepezil blunted the scopolamine effect to a greater extent than either drug alone. CONCLUSIONS: Exploratory analyses provide evidence for cognitive improvement through inverse agonism of the H3 histamine receptor and for cooperation between human cholinergic and histaminergic neurotransmitter systems. (ClinicalTrials.gov trial registration number: NCT01181310).
ESTHER : Cho_2011_Psychopharmacology.(Berl)_218_513
PubMedSearch : Cho_2011_Psychopharmacology.(Berl)_218_513
PubMedID: 21644059

Title : Metabolism of organophosphorus insecticides. IX. Distribution, excretion and metabolism of dimethoate in Prodenia litura F -
Author(s) : Zayed SMAD , Hassan A , Fakhr IMI
Ref : Biochemical Pharmacology , 17 :1339 , 1968

Title : Studies on the optically active isomers of 0,0-diethyl malathion and O,O-diethyl malaoxon -
Author(s) : Hassan A , Dauterman WS
Ref : Biochemical Pharmacology , 17 :1431 , 1968

Title : On the kinetics of inhibition of rat-brain acetylcholine esterase by sevin -
Author(s) : Hassan A , Abdel-Hamid FM , Bakig MRE
Ref : Zeit Naturforsch. , 22B :505 , 1967

Title : Metabolism of carbamate drugs. 1. Metabolism of 1-naphthyl N-methyl carbamate (sevin) in the rat -
Author(s) : Hassan A , Zayed SMAD , Abdel-Hamid FM
Ref : Biochemical Pharmacology , 15 :2045 , 1966

Title : Reversible inhibition of electric-organ cholinesterase by curare and curare-like agents -
Author(s) : Hassan A , Liepin LL
Ref : Biochimica & Biophysica Acta , 75 :397 , 1963