Firuzi O

References (13)

Title : Cinnamomum verum J. Presl. Bark essential oil: in vitro investigation of anti-cholinesterase, anti-BACE1, and neuroprotective activity - Saeedi_2022_BMC.Complement.Med.Ther_22_303
Author(s) : Saeedi M , Iraji A , Vahedi-Mazdabadi Y , Alizadeh A , Edraki N , Firuzi O , Eftekhari M , Akbarzadeh T
Ref : BMC Complement Med Ther , 22 :303 , 2022
Abstract : BACKGROUND: Cinnamomum verum J. Presl. (Lauraceae), Myrtus communis L. (Myrtaceae), Ruta graveolens L. (Rutaaceae), Anethum graveolens L. (Apiaceae), Myristica fragrans Houtt. (Myristicaceae), and Crocus sativus L. (Iridaceae) have been recommended for improvement of memory via inhalation, in Iranian Traditional Medicine (ITM). In this respect, the essential oils (EOs) from those plants were obtained and evaluated for cholinesterase (ChE) inhibitory activity as ChE inhibitors are theavailable drugs in the treatment of Alzheimer's disease (AD). METHODS: EOs obtained from the plants under investigation, were evaluated for their potential to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro based on the modified Ellman's method. The most potent EO was candidate for the investigation of its beta-secretase 1 (BACE1) inhibitory activity and neuroprotectivity. RESULTS: Among all EOs, C. verum demonstrated the most potent activity toward AChE and BChE with IC(50) values of 453.7 and 184.7g/mL, respectively. It also showed 62.64% and 41.79% inhibition against BACE1 atthe concentration of 500 and 100mg/mL, respectively. However, it depicted no neuroprotective potential against beta-amyloid (A)-induced neurotoxicity in PC12 cells. Also, identification of chemical composition of C. verum EO was achieved via gas chromatography-mass spectrometry (GC-MS) analysis and the major constituent; (E)-cinnamaldehyde, was detected as 68.23%. CONCLUSION: Potent BChE inhibitory activity of C. verum EO can be considered in the development of cinnamon based dietary supplements for the management of patients with advanced AD.
ESTHER : Saeedi_2022_BMC.Complement.Med.Ther_22_303
PubMedSearch : Saeedi_2022_BMC.Complement.Med.Ther_22_303
PubMedID: 36401242

Title : Imino-2H-chromene based derivatives as potential anti-Alzheimer's agents: Design, synthesis, biological evaluation and in silico study - Attarroshan_2021_Chem.Biodivers__
Author(s) : Attarroshan M , Firuzi O , Iraji A , Sharifi S , Tavakkoli M , Vesal M , Khoshneviszadeh M , Pirhadi S , Edraki N
Ref : Chem Biodivers , : , 2021
Abstract : A new series of imino-2H-chromene derivatives were rationally designed and synthesized as novel multifunctional agents against Alzheimer's disease. A set of phenylimino-2H-chromenes as well as the newly synthesized iminochromene derivatives were evaluated as BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitors. The results indicated that among the iminochromene set, 10c bearing fluorobenzyl moiety was the most potent BACE1 inhibitor with an IC 50 value 6.31 microM. In vitro anti-cholinergic activities demonstrated that compound 10a bearing benzyl pendant was the best inhibitor of AChE (% inhibition at 30 microM = 24.4) and BuChE (IC 50 = 3.3 microM). The kinetic study of 10a against BuChE was also performed and showed a mixed-type inhibition pattern. The neuroprotective assessment revealed that compound 11b , a phenylimino-2H-chromene derivative with hydroxyethyl moiety provided 32.3% protection at 25 microM against Abeta-induced PC12 neuronal cell damage. In addition, docking and simulation studies of the most potent compounds against BACE1 and BuChE confirmed the experimental results.
ESTHER : Attarroshan_2021_Chem.Biodivers__
PubMedSearch : Attarroshan_2021_Chem.Biodivers__
PubMedID: 34786830

Title : Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP\/PS1 Mice - Viayna_2021_J.Med.Chem_64_812
Author(s) : Viayna E , Coquelle N , Cieslikiewicz-Bouet M , Cisternas P , Oliva CA , Sanchez-Lopez E , Ettcheto M , Bartolini M , De Simone A , Ricchini M , Rendina M , Pons M , Firuzi O , Perez B , Saso L , Andrisano V , Nachon F , Brazzolotto X , Garcia ML , Camins A , Silman I , Jean L , Inestrosa NC , Colletier JP , Renard PY , Munoz-Torrero D
Ref : Journal of Medicinal Chemistry , 64 :812 , 2021
Abstract : The combination of the scaffolds of the cholinesterase inhibitor huprine Y and the antioxidant capsaicin results in compounds with nanomolar potencies toward human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that retain or improve the antioxidant properties of capsaicin. Crystal structures of their complexes with AChE and BChE revealed the molecular basis for their high potency. Brain penetration was confirmed by biodistribution studies in C57BL6 mice, with one compound (5i) displaying better brain/plasma ratio than donepezil. Chronic treatment of 10 month-old APP/PS1 mice with 5i (2 mg/kg, i.p., 3 times per week, 4 weeks) rescued learning and memory impairments, as measured by three different behavioral tests, delayed the Alzheimer-like pathology progression, as suggested by a significantly reduced Abeta42/Abeta40 ratio in the hippocampus, improved basal synaptic efficacy, and significantly reduced hippocampal oxidative stress and neuroinflammation. Compound 5i emerges as an interesting anti-Alzheimer lead with beneficial effects on cognitive symptoms and on some underlying disease mechanisms.
ESTHER : Viayna_2021_J.Med.Chem_64_812
PubMedSearch : Viayna_2021_J.Med.Chem_64_812
PubMedID: 33356266
Gene_locus related to this paper: human-ACHE

Title : Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease - Rastegari_2021_Mol.Divers__
Author(s) : Rastegari A , Safavi M , Vafadarnejad F , Najafi Z , Hariri R , Bukhari SNA , Iraji A , Edraki N , Firuzi O , Saeedi M , Mahdavi M , Akbarzadeh T
Ref : Mol Divers , : , 2021
Abstract : Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assay confirmed high potency of the title compounds. Among them, compounds 7l and 7b demonstrated high activity toward AChE and BChE with IC(50) values of 0.050 and 0.039 microM, respectively. Both compounds showed very good self-induced Abeta aggregation and AChE-induced inhibitory activity (79.4 and 71.4% for compound 7l and 61.8 and 58.6% for compound 7b, respectively). Also, 7l showed good anti-BACE1 activity with IC(50) value of 1.65 microM. The metal chelation test indicated the ability of compounds 7l and 7b to chelate biometals (Zn(2+), Cu(2+), and Fe(2+)). However, they showed no significant neuroprotectivity against Abeta-induced damage in PC12 cells. Evaluation of in vitro hepatotoxicity revealed comparable toxicity of compounds 7l and 7b with tacrine. In vivo studies by Morris water maze (MWM) task demonstrated that compound 7l significantly reversed scopolamine-induced memory deficit in rats. Finally, molecular docking studies of compounds 7l and 7b confirmed establishment of desired interactions with the AChE, BChE, and BACE1 active sites.
ESTHER : Rastegari_2021_Mol.Divers__
PubMedSearch : Rastegari_2021_Mol.Divers__
PubMedID: 34273065

Title : Design and synthesis of multi-target directed 1,2,3-triazole-dimethylaminoacryloyl-chromenone derivatives with potential use in Alzheimer's disease - Karimi_2020_BMC.Chem_14_64
Author(s) : Karimi Askarani H , Iraji A , Rastegari A , Abbas Bukhari SN , Firuzi O , Akbarzadeh T , Saeedi M
Ref : BMC Chem , 14 :64 , 2020
Abstract : To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Abeta aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC(50) value of 21.71 M for compound 10h as the most potent compound. Besides, compound 10h could inhibit self-induced Abeta(1-42) aggregation and AChE-induced Abeta aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver-Burk plot and molecular modeling study showed that compound 10h targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound 10h was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments.
ESTHER : Karimi_2020_BMC.Chem_14_64
PubMedSearch : Karimi_2020_BMC.Chem_14_64
PubMedID: 33134975

Title : Novel small molecule therapeutic agents for Alzheimer disease: Focusing on BACE1 and multi-target directed ligands - Iraji_2020_Bioorg.Chem_97_103649
Author(s) : Iraji A , Khoshneviszadeh M , Firuzi O , Edraki N
Ref : Bioorg Chem , 97 :103649 , 2020
Abstract : Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that effects 50 million people worldwide. In this review, AD pathology and the development of novel therapeutic agents targeting AD were fully discussed. In particular, common approaches to prevent Abeta production and/or accumulation in the brain including alpha-secretase activators, specific gamma-secretase modulators and small molecules BACE1 inhibitors were reviewed. Additionally, natural-origin bioactive compounds that provide AD therapeutic advances have been introduced. Considering AD is a multifactorial disease, the therapeutic potential of diverse multi target-directed ligands (MTDLs) that combine the efficacy of cholinesterase (ChE) inhibitors, MAO (monoamine oxidase) inhibitors, BACE1 inhibitors, phosphodiesterase 4D (PDE4D) inhibitors, for the treatment of AD are also reviewed. This article also highlights descriptions on the regulator of serotonin receptor (5-HT), metal chelators, anti-aggregants, antioxidants and neuroprotective agents targeting AD. Finally, current computational methods for evaluating the structure-activity relationships (SAR) and virtual screening (VS) of AD drugs are discussed and evaluated.
ESTHER : Iraji_2020_Bioorg.Chem_97_103649
PubMedSearch : Iraji_2020_Bioorg.Chem_97_103649
PubMedID: 32101780

Title : Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease - Saeedi_2020_Arch.Pharm.(Weinheim)__e2000101
Author(s) : Saeedi M , Safavi M , Allahabadi E , Rastegari A , Hariri R , Jafari S , Bukhari SNA , Mirfazli SS , Firuzi O , Edraki N , Mahdavi M , Akbarzadeh T
Ref : Arch Pharm (Weinheim) , :e2000101 , 2020
Abstract : In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.55 and 0.23 microM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (betaA) aggregation and beta-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.
ESTHER : Saeedi_2020_Arch.Pharm.(Weinheim)__e2000101
PubMedSearch : Saeedi_2020_Arch.Pharm.(Weinheim)__e2000101
PubMedID: 32657467

Title : Design and synthesis of novel arylisoxazole-chromenone carboxamides: Investigation of biological activities associated with Alzheimer's disease - Saeedi_2020_Chem.Biodivers__
Author(s) : Saeedi M , Rastegari A , Hariri R , Mirfazli SS , Mahdavi M , Edraki N , Firuzi O , Akbarzadeh T
Ref : Chem Biodivers , : , 2020
Abstract : A novel series of hybrid arylisoxazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5-(3-nitrophenyl)-N-(4-((2-oxo-2H-chromen-7-yl)oxy)phenyl)isoxazole-3-carboxamide (11h) depicted the most acetylcholinesterase (AChE) inhibitory activity (IC50 = 1.23 microM) and 5-(3-chlorophenyl)-N-(4-((2-oxo-2H-chromen-7-yl)oxy)phenyl)isoxazole-3-carboxamid e (11e) was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC50 = 9.71 microM). Compound 11h was further investigated for its BACE1 inhibitory activity as well as neuroprotectivity and metal chelating ability as important factors involved in onset and progress of Alzheimer's disease. It could inhibit BACE1 by 48.46% at 50 microM. Also, it showed 6.4% protection at 25 microM and satisfactory chelating ability toward Zn2+, Fe2+, and Cu2+ ions. Also, docking studies of compounds 11h and 11e confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.
ESTHER : Saeedi_2020_Chem.Biodivers__
PubMedSearch : Saeedi_2020_Chem.Biodivers__
PubMedID: 32154628

Title : Novel N-benzylpiperidine derivatives of 5-arylisoxazole-3-carboxamides as anti-Alzheimer's agents - Saeedi_2020_Arch.Pharm.(Weinheim)__e2000258
Author(s) : Saeedi M , Felegari P , Iraji A , Hariri R , Rastegari A , Mirfazli SS , Edraki N , Firuzi O , Mahdavi M , Akbarzadeh T
Ref : Arch Pharm (Weinheim) , :e2000258 , 2020
Abstract : The complex pathophysiology of Alzheimer's disease (AD) has prompted researchers to develop multitarget-directed molecules to find an effective therapy against the disease. In this context, a novel series of N-(1-benzylpiperidin-4-yl)-5-arylisoxazole-3-carboxamide derivatives were designed, synthesized, and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro biological evaluation demonstrated that compound 4e was the best AChE (IC(50) = 16.07 M) and BuChE inhibitor (IC(50) = 15.16 M). A kinetic study of 4e was also conducted, which presented a mixed-type inhibition for both enzymes. Molecular docking studies revealed that compound 4e fitted well into the active sites of AChE and BuChE, forming stable and strong interactions with key residues Glu199, Trp84, Asp72, Tyr121, and Phe288 in AChE and His438, Trp82, Ala328, Tyr332, Phe329, Thr120, and Pro285 in BuChE. Besides, the inhibition of BACE1 by 4e and the biometal chelation activity of 4e were measured. The neuroprotective assessment revealed that 4e exhibited 23.2% protection at 50 microM toward amyloid-beta-induced PC12 neuronal cells. Overall, this study exhibited that compound 4e was a promising compound targeting multiple factors associated with AD.
ESTHER : Saeedi_2020_Arch.Pharm.(Weinheim)__e2000258
PubMedSearch : Saeedi_2020_Arch.Pharm.(Weinheim)__e2000258
PubMedID: 33226157

Title : Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti-Alzheimer's Agents - Mahdavi_2019_Chem.Biodivers_16_e1800488
Author(s) : Mahdavi M , Hariri R , Mirfazli SS , Lotfian H , Rastergari A , Firuzi O , Edraki N , Larijani B , Akbarzadeh T , Saeedi M
Ref : Chem Biodivers , 16 :e1800488 , 2019
Abstract : Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal-chelating properties. Among the synthesized compounds, 14-amino-13-(3-nitrophenyl)-2,3,4,13-tetrahydro-1H-benzo[6,7]chromeno[2,3-b]quino line-7,12-dione (6m) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 s of 0.86 and 6.03 mum, respectively. Also, the compound could inhibit beta-secretase 1 (BACE1) with IC50 =19.60 mum and showed metal chelating ability toward Cu(2+) , Fe(2+) , and Zn(2+) . In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.
ESTHER : Mahdavi_2019_Chem.Biodivers_16_e1800488
PubMedSearch : Mahdavi_2019_Chem.Biodivers_16_e1800488
PubMedID: 30720917

Title : Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation - Yazdani_2019_Bioorg.Chem_84_363
Author(s) : Yazdani M , Edraki N , Badri R , Khoshneviszadeh M , Iraji A , Firuzi O
Ref : Bioorg Chem , 84 :363 , 2019
Abstract : Alzheimer's disease (AD) is a complex neurological disorder with diverse underlying pathological processes. Several lines of evidence suggest that BACE1 is a key enzyme in the pathogenesis of AD and its inhibition is of particular importance in AD treatment. Ten new 3-hydrazinyl-1,2,4-triazines bearing pendant aryl phenoxy methyl-1,2,3-triazole were synthesized as multifunctional ligands against AD. We show that compounds containing Cl and NO(2) groups at the para position of the phenyl ring, namely compounds 7c (IC(50) = 8.55 +/- 3.37 microM) and 7d (IC(50) = 11.42 +/- 2.01 microM), possess promising BACE1 inhibitory potential. Furthermore, we assessed the neuroprotective activities of 7c and 7d derivatives in PC12 neuronal cell line, which showed moderate protection against amyloid beta peptide toxicity. In addition, compound 7d demonstrated metal chelating activity and moderate antioxidant potential (IC(50) = 44.42 +/- 7.33 microM). Molecular docking studies of these molecules revealed high-affinity binding to several amino acids of BACE1, which are essential for efficient inhibition. These results demonstrate that 1,2,4-triazine derivatives bearing an aryl phenoxy methyl-1,2,3-triazole have promising properties as therapeutic agents for AD.
ESTHER : Yazdani_2019_Bioorg.Chem_84_363
PubMedSearch : Yazdani_2019_Bioorg.Chem_84_363
PubMedID: 30530107

Title : Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study - Vafadarnejad_2019_Bioorg.Chem_92_103192
Author(s) : Vafadarnejad F , Karimpour-Razkenari E , Sameem B , Saeedi M , Firuzi O , Edraki N , Mahdavi M , Akbarzadeh T
Ref : Bioorg Chem , 92 :103192 , 2019
Abstract : A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC50=5.96microM) and compound 5j also from the same series of compounds containing phenyl group connected to isoxazole ring demonstrated the most promising inhibitory activity against BChE (IC50=0.32microM). Also, kinetic study demonstrated competitive inhibition mode for both AChE and BChE inhibitory activity. Docking study was also performed for those compounds and desired interactions with those active site amino acid residues were confirmed through hydrogen bonding as well as pi-pi and pi-anion interactions. In addition, the most potent compounds were tested against BACE1 and their neuroprotectivity on Abeta-treated neurotoxicity in PC12 cells which depicted negligible activity. It should be noted that most of the synthesized compounds from both categories 5a-i and 5j-q showed a significant selectivity toward BChE. However, series 5j-q were more active toward AChE than series 5a-i.
ESTHER : Vafadarnejad_2019_Bioorg.Chem_92_103192
PubMedSearch : Vafadarnejad_2019_Bioorg.Chem_92_103192
PubMedID: 31446239

Title : Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole-Phenylpiperazine Derivatives - Saeedi_2019_Chem.Biodivers_16_e1800433
Author(s) : Saeedi M , Mohtadi-Haghighi D , Mirfazli SS , Mahdavi M , Hariri R , Lotfian H , Edraki N , Iraji A , Firuzi O , Akbarzadeh T
Ref : Chem Biodivers , 16 :e1800433 , 2019
Abstract : In this work, a novel series of arylisoxazole-phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5-(2-chlorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5c) was the most potent AChE inhibitor with IC50 of 21.85 mum. It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5-(2-fluorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5a) was the most active anti-BChE derivative (IC50 =51.66 mum). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC50 =76.78 mum. Finally, neuroprotectivity of compound 5c on Abeta-treated neurotoxicity in PC12 cells depicted low activity.
ESTHER : Saeedi_2019_Chem.Biodivers_16_e1800433
PubMedSearch : Saeedi_2019_Chem.Biodivers_16_e1800433
PubMedID: 30460743