Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies

Peytam, Fariba; Adib, Mehdi; Shourgeshty, Reihaneh; Mohammadi‐Khanaposhtani, Maryam; Jahani, Mehdi; Imanparast, Somaye; Faramarzi, Mohammad Ali; Mahdavi, Mohammad; Moghadamnia, Ali Akbar; Rastegar, Hossein; Larijani, Bagher

doi:10.1007/s11030-019-09925-8

Cited by 29 publications

(10 citation statements)

References 37 publications

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“…Moreover, it is well documented that taking advantage of the other commercially available therapies controls only 36% of type II DM patients to achieve glycemic control [ 21 ]. As a result, the need for novel and safe α-glucosidase inhibitors to control the blood sugar level is critical [ 22 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

et al. 2022

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A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a–o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a–o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

et al. 2022

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“…According to a literature survey heterocyclic pyrazole rings, whether free or hybridized with other active pharmacophores exhibit many biological activities (Bansal et al, 2019; EI Shehry & Ghorab, 2018; Khan et al, 2016; Koca et al, 2013; Peytam et al, 2020; Ragab et al, 2013; Taher et al, 2019; Turkan et al, 2019). Pyrazole is the active component of several anti‐diabetic drugs (Damavand & Jadhav, 2015; Rammohan et al, 2020), where, pyrazole with thiosemicarbazones exhibited potent DPP‐4 inhibitory effects (Sever et al, 2020), pyrazole‐3‐carbohydrazone derivatives have DPP‐4 inhibitory activity (Wu et al, 2012), quinazolinone‐pyrazole scaffolds were exhibited anti‐diabetic activity (Azimi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Lead modification via computational studies: Synthesis of pyrazole‐containing β‐amino carbonyls for the treatment of type 2 diabetes

et al. 2022

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This article describes studies on the design, synthesis, and biological evaluation of pyrazole‐containing β‐amino carbonyl compounds (5a–5q) as DPP‐4 inhibitors and anti‐diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO3)3) catalyst in the presence of ethanol and produced pyrazole‐containing β‐amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP‐4 enzyme (PDB: 2OLE), compounds 5d, 5h, 5j, and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme‐based in vitro DPP‐4 inhibitory activity, and 5d, 5h, 5i, 5j, and 5k exhibited IC50 toward DPP‐4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j, was further selected for in vivo anti‐diabetic activity using an STZ‐induced diabetic mice model, and 5j showed a significant diabetic control effect.

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“…In silico based studies have been conducted for evaluating the efficacy of several pyrazole derivatives for assessing different types of biological properties, including anticancer activity [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. In the present study, using molecular docking and molecular dynamic (MD) simulation, a total of 63 pyrazole derivatives were computationally investigated for assessing the modulatory or inhibitory effects against the cited protein targets linked to diverse cancer types.…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC—Application towards Cancer Therapeutics

Bennani

Karrouchi

Doudach

et al. 2022

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Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein–ligand contact maps were derived from trajectories of simulated protein–ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein–ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.

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Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies

Cited by 29 publications

References 37 publications

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

Lead modification via computational studies: Synthesis of pyrazole‐containing β‐amino carbonyls for the treatment of type 2 diabetes

In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC—Application towards Cancer Therapeutics

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