Alireza Moradi - Academia.edu (original) (raw)
Papers by Alireza Moradi
EXCLI Journal, 2014
By considering stem cell-based therapies as a new hope for the treatment of some tragic diseases,... more By considering stem cell-based therapies as a new hope for the treatment of some tragic diseases, marrow stromal cells or marrow mesenchymal stem cells (MSCs) were considered as a suitable and safe multipotential cell source for this new therapeutic approach. For this purpose, many investigations have been performed on differentiation of MSCs toward specific cell lines to overcome the demand for providing the organ specific cells for cell therapy or preparation of engineered tissues. In the present study, differentiation of MSCs to endothelial cells (ECs) by mechanical and chemical stimulation was evaluated. Fluid shear stress (FSS) was used as mechanical inducer, while platelet lysate (PL) and estradiol (E) were used as chemical induction factors. MSCs were placed under FSS with different forces (2, 5 and 10dyn/cm2) for different periods (6, 12 and 24 hours). In some groups, PL and E were added to the culture media to evaluate their effect on expression of EC specific markers. This...
Bioorganic & medicinal chemistry, Jan 29, 2018
Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a u... more Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl Pyridine derivatives were designed synthesized and evaluated as butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9-yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most potent anti-BChE activity (IC value = 0.073 μM), the highest BChE selectivity and mixed-type inhibition. Docking study revealed that 8f interacted with the peripheral site, the choline binding site, catalytic site and the acyl pocket of BChE. Physicochemical properties were accurate to Lipinski's rule. In addition, compound 8f demonstrated neuroprotective activity at 10 µM. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100 µM and 10 µM respectively. The in-vivo st...
![Research paper thumbnail of New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease](https://attachments.academia-assets.com/102960375/thumbnails/1.jpg)
](European Journal of Medicinal Chemistry, 2017
A series of tacrine-like compounds 7a-u were designed and synthesized as potent AChE inhibitors w... more A series of tacrine-like compounds 7a-u were designed and synthesized as potent AChE inhibitors with high selectivity, low toxicity on hepatocytes, neuroprotective and and βamyloid aggregation inhibitory activity.
Basic and clinical neuroscience, 2015
Alzheimer's disease (AD) is an age-related neurodegenerative disease, which impairs memory an... more Alzheimer's disease (AD) is an age-related neurodegenerative disease, which impairs memory and cognitive function. Walnuts are a dietary source of polyphenols, antioxidants and other compounds with health beneficial effects. These characteristic of walnuts make them perfect candidates for evaluation of their possible effects on neurodegenerative diseases. Therefore the present study was designed to investigate the effects of walnuts consumption (2%, 6% and 9% walnut diets) on memory enhancement and acetylcholinesterase (AChE) activity of brain in scopolamine-induced amnesic rats. Learning, memory and locomotor activity parameters were evaluated using Morris water maze (MWM), passive avoidance and rotarod tests. Our results showed that consumption of walnuts at doses of 6% and 9% significantly restored the scopolamine-induced memory impairments in the MWM and passive avoidance tests. Moreover, the potential of walnuts to prevent scopolamine neurotoxicity was also reflected by the...
European Journal of Medicinal Chemistry, 2015
Chagas disease and Human African trypanosomiasis (HAT) are important public health issues in Lati... more Chagas disease and Human African trypanosomiasis (HAT) are important public health issues in Latin American and sub-Saharan African countries, respectively, and are responsible for a significant number of deaths. The drugs currently used to treat Chagas disease and HAT present efficacy, toxicity, and/or resistance issues; thus, there is a clear need for the discovery of novel targets and drug candidates to combat these diseases. In recent years, much effort has been made to find inhibitors of cruzain and rhodesain, which are promising targets for the design of novel trypanocidal compounds, since they are essential for parasite survival. Many reviews covering the design of novel cruzain and rhodesain inhibitors have been published; however, none have focused on the chemistry of the inhibitors. Thus, in the present work we revised the synthetic strategies and routes for the preparation of relevant classes of cruzain and rhodesain inhibitors. Perhaps the most important are the vinyl sulfone derivatives, and a very efficient synthetic strategy based on the Horner-Wadsworth-Emmons reaction was developed to yield these compounds. Modern approaches such as the asymmetric addition of substituted ethynyllithium to Nsulfinyl ketimines were used to produce the chiral alkynes that were employed in the preparation of important chiral triazole derivatives (potent cruzain inhibitors) and chiral HPLC resolution was used for the preparation of enantiopure 3-bromoisoxazoline derivatives (rhodesain inhibitors). Moreover, we also highlight the most important activity results and updated SAR results.
![Research paper thumbnail of New tetracyclic tacrine analogs containing pyrano[2,3-c]pyrazole: Efficient synthesis, biological assessment and docking simulation study](https://attachments.academia-assets.com/102960374/thumbnails/1.jpg)
](European Journal of Medicinal Chemistry, 2015
A new series of tacrine-based acetylcholinesterase (AChE) inhibitors 7ael were designed by replac... more A new series of tacrine-based acetylcholinesterase (AChE) inhibitors 7ael were designed by replacing the benzene ring of tacrine with aryl-dihydropyrano[2,3-c]pyrazole. The poly-functionalized hybrid molecules 7ael were efficiently synthesized through multi-component reaction and subsequent Friedl€ ander reaction between the obtained pyrano[2,3-c]pyrazoles and cyclohexanone. Most of target compounds showed potent and selective anti-AChE activity at sub-micromolar range. The most potent compound 7h bearing a 3,4-dimethoxyphenyl group was more active than reference drug tacrine. The representative compound 7h could significantly protect neurons against oxidative stress as potent as quercetin at low concentrations. The docking study of compound 7h with AChE enzyme revealed that the (R)-enantiomer binds preferably to CAS while the (S)-enantiomer prone to be a PAS binder.
Medicinal Chemistry Research, 2012
In the pursuit of novel antibacterial agents with the 2-thiazolylimino-4-thiazolidinone as a core... more In the pursuit of novel antibacterial agents with the 2-thiazolylimino-4-thiazolidinone as a core structure, a series of 5-nitro-heteroarylidene and 5-(2-oxoindolin-3ylidene) analogs of 2-thiazolylimino-5-arylidene-4-thiazolidinone were synthesized and their antibacterial activities were evaluated against some strains of Gram-positive and Gram-negative bacteria, as well as Helicobacter pylori strains. Biological data indicated that 5-nitrofuran analog 5a and 5-nitroimidazole analog 7a containing no substitutions on the thiazole ring were the most potent compounds.
European Journal of Medicinal Chemistry, 2013
Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesi... more Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC50 = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study.
European Journal of Medicinal Chemistry, 2013
A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinestera... more A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinesterase (AChE) inhibitors which could be considered for Alzheimer's disease therapeutics. Among the 19 coumarin-derived compounds tested toward Electrophorus electricus acetylcholinesterase (eelAChE) and horse serum butyrylcholinesterase (eqBChE), N-(1-benzylpiperidin-4-yl)acetamide derivative 4m displayed highest AChE inhibitory activity (IC 50 ¼ 1.2 mM) and good selectivity (37 times). The docking study of the most potent compound 4m, indicated that Phe330 is responsible for ligand recognition and trafficking by forming p-cation interaction with benzylpiperidine moiety. Furthermore, the formation of an additional pep interaction between coumarin moiety and Trp279 of peripheral anionic site could stabilize the ligand in the active site resulting in more potent inhibition of the enzyme.
Bioorganic & Medicinal Chemistry, 2012
A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and bio... more A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC 50 in which compound 3r (IC 50 = 0.11 nM) was the most active compound against acetylcholinesterase enzyme.
Archiv der Pharmazie, 2010
A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic... more A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds having an unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl ring showed moderate to high analgesic or antiinflammatory activity in comparison to mefenamic acid as the reference drug. The compounds with highest anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition assays and showed moderate to good COX-1 and weak COX-2 inhibition activities.
EXCLI Journal, 2014
By considering stem cell-based therapies as a new hope for the treatment of some tragic diseases,... more By considering stem cell-based therapies as a new hope for the treatment of some tragic diseases, marrow stromal cells or marrow mesenchymal stem cells (MSCs) were considered as a suitable and safe multipotential cell source for this new therapeutic approach. For this purpose, many investigations have been performed on differentiation of MSCs toward specific cell lines to overcome the demand for providing the organ specific cells for cell therapy or preparation of engineered tissues. In the present study, differentiation of MSCs to endothelial cells (ECs) by mechanical and chemical stimulation was evaluated. Fluid shear stress (FSS) was used as mechanical inducer, while platelet lysate (PL) and estradiol (E) were used as chemical induction factors. MSCs were placed under FSS with different forces (2, 5 and 10dyn/cm2) for different periods (6, 12 and 24 hours). In some groups, PL and E were added to the culture media to evaluate their effect on expression of EC specific markers. This...
Bioorganic & medicinal chemistry, Jan 29, 2018
Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a u... more Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl Pyridine derivatives were designed synthesized and evaluated as butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9-yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most potent anti-BChE activity (IC value = 0.073 μM), the highest BChE selectivity and mixed-type inhibition. Docking study revealed that 8f interacted with the peripheral site, the choline binding site, catalytic site and the acyl pocket of BChE. Physicochemical properties were accurate to Lipinski's rule. In addition, compound 8f demonstrated neuroprotective activity at 10 µM. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100 µM and 10 µM respectively. The in-vivo st...
European Journal of Medicinal Chemistry, 2017
A series of tacrine-like compounds 7a-u were designed and synthesized as potent AChE inhibitors w... more A series of tacrine-like compounds 7a-u were designed and synthesized as potent AChE inhibitors with high selectivity, low toxicity on hepatocytes, neuroprotective and and βamyloid aggregation inhibitory activity.
Basic and clinical neuroscience, 2015
Alzheimer's disease (AD) is an age-related neurodegenerative disease, which impairs memory an... more Alzheimer's disease (AD) is an age-related neurodegenerative disease, which impairs memory and cognitive function. Walnuts are a dietary source of polyphenols, antioxidants and other compounds with health beneficial effects. These characteristic of walnuts make them perfect candidates for evaluation of their possible effects on neurodegenerative diseases. Therefore the present study was designed to investigate the effects of walnuts consumption (2%, 6% and 9% walnut diets) on memory enhancement and acetylcholinesterase (AChE) activity of brain in scopolamine-induced amnesic rats. Learning, memory and locomotor activity parameters were evaluated using Morris water maze (MWM), passive avoidance and rotarod tests. Our results showed that consumption of walnuts at doses of 6% and 9% significantly restored the scopolamine-induced memory impairments in the MWM and passive avoidance tests. Moreover, the potential of walnuts to prevent scopolamine neurotoxicity was also reflected by the...
European Journal of Medicinal Chemistry, 2015
Chagas disease and Human African trypanosomiasis (HAT) are important public health issues in Lati... more Chagas disease and Human African trypanosomiasis (HAT) are important public health issues in Latin American and sub-Saharan African countries, respectively, and are responsible for a significant number of deaths. The drugs currently used to treat Chagas disease and HAT present efficacy, toxicity, and/or resistance issues; thus, there is a clear need for the discovery of novel targets and drug candidates to combat these diseases. In recent years, much effort has been made to find inhibitors of cruzain and rhodesain, which are promising targets for the design of novel trypanocidal compounds, since they are essential for parasite survival. Many reviews covering the design of novel cruzain and rhodesain inhibitors have been published; however, none have focused on the chemistry of the inhibitors. Thus, in the present work we revised the synthetic strategies and routes for the preparation of relevant classes of cruzain and rhodesain inhibitors. Perhaps the most important are the vinyl sulfone derivatives, and a very efficient synthetic strategy based on the Horner-Wadsworth-Emmons reaction was developed to yield these compounds. Modern approaches such as the asymmetric addition of substituted ethynyllithium to Nsulfinyl ketimines were used to produce the chiral alkynes that were employed in the preparation of important chiral triazole derivatives (potent cruzain inhibitors) and chiral HPLC resolution was used for the preparation of enantiopure 3-bromoisoxazoline derivatives (rhodesain inhibitors). Moreover, we also highlight the most important activity results and updated SAR results.
European Journal of Medicinal Chemistry, 2015
A new series of tacrine-based acetylcholinesterase (AChE) inhibitors 7ael were designed by replac... more A new series of tacrine-based acetylcholinesterase (AChE) inhibitors 7ael were designed by replacing the benzene ring of tacrine with aryl-dihydropyrano[2,3-c]pyrazole. The poly-functionalized hybrid molecules 7ael were efficiently synthesized through multi-component reaction and subsequent Friedl€ ander reaction between the obtained pyrano[2,3-c]pyrazoles and cyclohexanone. Most of target compounds showed potent and selective anti-AChE activity at sub-micromolar range. The most potent compound 7h bearing a 3,4-dimethoxyphenyl group was more active than reference drug tacrine. The representative compound 7h could significantly protect neurons against oxidative stress as potent as quercetin at low concentrations. The docking study of compound 7h with AChE enzyme revealed that the (R)-enantiomer binds preferably to CAS while the (S)-enantiomer prone to be a PAS binder.
Medicinal Chemistry Research, 2012
In the pursuit of novel antibacterial agents with the 2-thiazolylimino-4-thiazolidinone as a core... more In the pursuit of novel antibacterial agents with the 2-thiazolylimino-4-thiazolidinone as a core structure, a series of 5-nitro-heteroarylidene and 5-(2-oxoindolin-3ylidene) analogs of 2-thiazolylimino-5-arylidene-4-thiazolidinone were synthesized and their antibacterial activities were evaluated against some strains of Gram-positive and Gram-negative bacteria, as well as Helicobacter pylori strains. Biological data indicated that 5-nitrofuran analog 5a and 5-nitroimidazole analog 7a containing no substitutions on the thiazole ring were the most potent compounds.
European Journal of Medicinal Chemistry, 2013
Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesi... more Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC50 = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study.
European Journal of Medicinal Chemistry, 2013
A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinestera... more A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinesterase (AChE) inhibitors which could be considered for Alzheimer's disease therapeutics. Among the 19 coumarin-derived compounds tested toward Electrophorus electricus acetylcholinesterase (eelAChE) and horse serum butyrylcholinesterase (eqBChE), N-(1-benzylpiperidin-4-yl)acetamide derivative 4m displayed highest AChE inhibitory activity (IC 50 ¼ 1.2 mM) and good selectivity (37 times). The docking study of the most potent compound 4m, indicated that Phe330 is responsible for ligand recognition and trafficking by forming p-cation interaction with benzylpiperidine moiety. Furthermore, the formation of an additional pep interaction between coumarin moiety and Trp279 of peripheral anionic site could stabilize the ligand in the active site resulting in more potent inhibition of the enzyme.
Bioorganic & Medicinal Chemistry, 2012
A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and bio... more A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC 50 in which compound 3r (IC 50 = 0.11 nM) was the most active compound against acetylcholinesterase enzyme.
Archiv der Pharmazie, 2010
A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic... more A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds having an unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl ring showed moderate to high analgesic or antiinflammatory activity in comparison to mefenamic acid as the reference drug. The compounds with highest anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition assays and showed moderate to good COX-1 and weak COX-2 inhibition activities.