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Öğe 4-Phenylthiazol-1,2,3-triazole derivatives as new potential α-glucosidase and α-amylase inhibitors(Elsevier, 2025) Ghanbarlou, Mehdi; Karimian, Somaye; Doraghi, Fatemeh; Dadgar, Armin; Senol, lbilge Merve; Larijani, Bagher; Mohammadi-Khanaposhtani, MaryamType-2 diabetes mellitus (T2DM) can be managed by targeting carbohydrate hydrolases such as alpha-glucosidase and alpha-amylase. In this regard, a new 4-phenylthiazol-benzamide-1,2,3-triazole-N-phenylacetamide scaffold was designed via molecular hybridization (MH), and 15 derivatives (9a-o) were synthesized by changing the substituents on the phenyl ring of the N-phenylacetamide moiety. These compounds were evaluated as potent alpha-glucosidase and alpha-amylase inhibitors. The in vitro results indicated that the half maximal inhibitory concentration (IC50) of compounds 9a-o ranged from 10.71 to 42.35 nM against alpha-glucosidase and 49.17-81.94 nM against alpha-amylase while the IC50 values of the positive control acarbose against alpha-glucosidase and alpha-amylase were 62.03 and 105.44 nM, respectively. The most potent compound against both digestive enzymes was compound 9g with two methyl groups on positions 2 and 3 of the phenyl ring of the N-phenylacetamide moiety. Compound 9g was 5.79 and 2.14 times more potent than acarbose against alpha-glucosidase and alpha-amylase, respectively. The docking study showed that all the synthesized compounds (9a-o) attached to the active sites of alpha-glucosidase and alpha-amylase with lower binding energies in comparison to acarbose. Furthermore, according to the dynamics simulation, compound 9g established a stable complex with the active site of alpha-glucosidase.Öğe Design of novel benzimidazole-propane hydrazide derivatives as α-glucosidase and α-amylase inhibitors: in vitro and in silico studies(Springer Birkhauser, 2025) Mohammadizadeh, Shiva; Karimian, Somaye; Dastyafteh, Navid; Noori, Milad; Doraghi, Fatemeh; Mohammadi-Khanaposhtani, Maryam; Larijani, BagherA new series of benzimidazole-propane hydrazide derivatives 9a-k were designed, synthesized, and evaluated for their inhibition ability against alpha-glucosidase and alpha-amylase. The results of the in vitro evaluations showed that all the tested compounds exhibited significant inhibition against alpha-glucosidase and alpha-amylase. Title compounds 9a-k exhibited varying degrees of inhibitory ability against alpha-glucosidase, with IC50 values in the range of 73.86-151.54 nM, in comparison to the standard acarbose drug with IC50 value of 174.50 nM. Similarly, these compounds demonstrated varying degrees of alpha-amylase inhibitory ability (the IC50 values ranged from 42.50 to 78.58 nM in comparison to acarbose with IC50 of 79.05 nM). Among the synthesized compounds, compound 9 h demonstrated the highest alpha-glucosidase inhibitory activity and compound 9 f demonstrated the highest anti-alpha-amylase activity. To further investigation on the potential of these derivatives as alpha-glucosidase and alpha-amylase inhibitors, molecular docking were conducted on all the synthesized compounds 9a-k. Docking results were in agreement with in vitro results. Molecular dynamics of compound 9 h showed that complex compound 9h-alpha-glucosidase had acceptable stability and flexibility. Calculations of physicochemical properties of compound 9a-k showed that these compounds fallowed of the main drug-likeness rules. Furthermore, the prediction of pharmacokinetics and toxicity profiles of compound 9 h showed that this compound can be considered as a lead drug structure.Öğe New benzimidazole-indole-amide derivatives as potent α-glucosidase and acetylcholinesterase inhibitors(Wiley-V C H Verlag Gmbh, 2024) Naimi, Narges; Karimian, Somaye; Dastyafteh, Navid; Noori, Mild; Mohammadi-Khanaposhtani, Maryam; Dadgar, Armin; Larijani, BagherNew derivatives 6a-m with benzimidazole-indole-amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on alpha-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the alpha-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose. Moreover, the anti-AChE activity of these compounds, with the exception of one compound, was better than that of tacrine (standard inhibitor). The most potent compound against alpha-glucosidase was 3-methylphenyl derivative 6i and the most potent compound against AChE was 3,4-dimethoxyphenethyl derivative 6m. All the synthesized compounds were placed in the active sites of alpha-glucosidase and AChE by in silico docking method and the obtained binding energies were approximately in agreement with the in vitro observed data. Interaction modes of the most potent compounds 6i and 6m demonstrated that these compounds interacted with important residues of their target enzymes. Molecular dynamics simulation was conducted specifically on compound 6i in complex with alpha-glucosidase to obtain deeper insights into the behavior of this molecule. Furthermore, in silico pharmacokinetic and toxicity studies on the most potent compound predicted that these compounds have good profiles in terms of oral absorption and toxicity.Öğe Rhodanine-pyridinium derivatives as a new category of cholinesterase inhibitors: Design, synthesis, in vitro and in silico enzymatic evaluations(Elsevier, 2025) Noori, Milad; Karimian, Somaye; Dastyafteh, Navid; Ghafouri, Seyedeh Niloufar; Mohammadi-Khanaposhtani, Maryam; Safapoor, Sajedeh; Ghomi, Minoo KhaliliRhodanine-pyridinium derivatives 10a-q were designed and synthesized based on reported cholinesterase (ChE) inhibitors and evaluated as potent anti-Alzheimer's disease agents. The in vitro anti-ChE activity of the title compounds was evaluated against two main forms of this enzyme: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The obtained in vitro results showed that all the synthesized derivatives were more potent than positive control tacrine against AChE. Moreover, most of the new synthesized compounds were more potent than tacrine against BChE. Among the synthesized compounds, compound 10p was the most potent compound against AChE and compound 10f was the most potent compound against BChE. In vitro kinetic study demonstrated that compounds 10p and 10f were competitive inhibitors against AChE and BChE, respectively. Both these compounds had a 4-CF3 substituent on phenyl ring of benzyl pyridinium moiety. Docking study on compounds 10p and 10f demonstrated that these compounds with favorable binding energies in comparison to tacrine attached to the active sites of AChE and BChE. Molecular dynamics simulations were performed on the 10p-AChE and 10f-BChE complexes to gain deeper insights into the behavior of these compounds in the active sites of target enzymes.
