Pharmacophore studies of 1, 3, 4-oxadiazole nucleus: Lead compounds as α-glucosidase inhibitors

Khan, Haroon; Zafar, Maryam; Patel, Seema; Shah, SM Mukarrum; Bishayee, Anupam

doi:10.1016/j.fct.2019.05.006

Cited by 13 publications

(5 citation statements)

References 36 publications

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“…Pharmacophore screened compounds were further subjected for docking into the active site of CXCL12. Docking studies were performed by using the default parameter implemented in the Molecular Operating Environment (MOE) program 2019.01 [ 29 ]. Form docking hit compounds and top best pose on the basis of docking score were selected for further evaluation.…”

Section: Methodsmentioning

confidence: 99%

Discovery of Potential Chemical Probe as Inhibitors of CXCL12 Using Ligand-Based Virtual Screening and Molecular Dynamic Simulation

2020

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CXCL12 are small pro-inflammatory chemo-attractant cytokines that bind to a specific receptor CXCR4 with a role in angiogenesis, tumor progression, metastasis, and cell survival. Globally, cancer metastasis is a major cause of morbidity and mortality. In this study, we targeted CXCL12 rather than the chemokine receptor (CXCR4) because most of the drugs failed in clinical trials due to unmanageable toxicities. Until now, no FDA approved medication has been available against CXCL12. Therefore, we aimed to find new inhibitors for CXCL12 through virtual screening followed by molecular dynamics simulation. For virtual screening, active compounds against CXCL12 were taken as potent inhibitors and utilized in the generation of a pharmacophore model, followed by validation against different datasets. Ligand based virtual screening was performed on the ChEMBL and in-house databases, which resulted in successive elimination through the steps of pharmacophore-based and score-based screenings, and finally, sixteen compounds of various interactions with significant crucial amino acid residues were selected as virtual hits. Furthermore, the binding mode of these compounds were refined through molecular dynamic simulations. Moreover, the stability of protein complexes, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and radius of gyration were analyzed, which led to the identification of three potent inhibitors of CXCL12 that may be pursued in the drug discovery process against cancer metastasis.

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Section: Methodsmentioning

confidence: 99%

Discovery of Potential Chemical Probe as Inhibitors of CXCL12 Using Ligand-Based Virtual Screening and Molecular Dynamic Simulation

2020

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“…Oxadiazole was generated by the process of refluxing component 4 under the same conditions that were present before the production of compound 5, which was formed by the reaction of component 4 with CS2 and potassium hydroxide. Compound 5 was produced through the production of oxadiazole (6). Because of the reaction of ( 6) with benzyl bromide, we were able to get the substituted oxadiazole as a result (7).…”

Section: From Chalconesmentioning

confidence: 99%

“…These compounds may be found in a wide variety of medicines. It has been shown that compounds based on 1,3,4-oxadiazole have specific anti-edema and anti-inflammatory effects, and these activities have been demonstrated 6 .…”

Section: Introductionmentioning

confidence: 99%

Occurrence, Chemistry and Synthesis of Various Novel Methods of Oxadiazole

-¹

2023

IJFMR

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Oxadiazoles are a kind of heterocyclic molecule that can be identified by their five-membered ring structure, two azo groups, and a single oxygen atom in their make-up. These characteristics allow them to be distinguished from other heterocyclic compounds. Because of these features, it is possible to differentiate them from several other heterocyclic compounds. They have the highest importance and relevance in the area of heterocyclic chemistry, which is also where they have the most value. They are of the biggest significance. Research is being conducted on it in substantial amounts due to the fact that it has the potential to function as a starting point for the synthesis of bioactive molecules that are beneficial to the body. This article provides a brief discussion of the physicochemical features of oxadiazole, including its spectra and a few examples of how it may be synthesised. The article can be found here. The pharmacological effects of oxadiazole derivatives were investigated by our team of researchers, and the findings indicated that these compounds had a number of positive benefits, including anti-inflammatory, anti-cancer, anti-fungal, anti-osteoporotic, and anti-microbial properties. In this piece, we will have a brief discussion on both synthetic and naturally occurring medications that include the oxadiazole ring in addition to the moiety. This talk will focus on pharmaceuticals that have been manufactured. The production of these compounds may take place in a laboratory, or they may be found occurring naturally in their natural environments.

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“…1,3,4-Oxadiazole moiety is a heterocyclic skeleton with single O, two N, and two C atoms with compromised aromaticity and enhanced diene character [ 23 ]. Compounds belonging to this class of heterocycles have expressed a tumultuous therapeutic potential as antimicrobial [ 24 , 25 , 26 , 27 ], antiepileptic [ 28 , 29 , 30 , 31 , 32 ], anticancer [ 33 , 34 , 35 , 36 ], hypoglycemic [ 37 , 38 , 39 , 40 ], antiviral [ 41 , 42 , 43 , 44 , 45 , 46 ], and anti-inflammatory [ 47 , 48 , 49 , 50 , 51 ] agents. Meanwhile, the chemistry and biological potential of 1,3,4-oxadiazoles have been thoroughly reviewed recently [ 52 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Novel S-alkyl Phthalimide- and S-benzyl-oxadiazole-quinoline Hybrids as Inhibitors of Monoamine Oxidase and Acetylcholinesterase

et al. 2022

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New S-alkyl phthalimide 5a–f and S-benzyl 6a–d analogs of 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole-2-thiol (4) were prepared by reacting 4 with N-bromoalkylphthalimide and CF3-substituted benzyl bromides in excellent yields. Spectroscopic techniques were employed to elucidate the structures of the synthesized molecules. The inhibition activity of newly synthesized molecules toward MAO-A, MAO-B, and AChE enzymes, was also assessed. All these compounds showed activity in the submicromolar range against all enzymes. Compounds 5a and 5f were found to be the most potent compounds against MAO-A (IC50 = 0.91 ± 0.15 nM) and MAO-B (IC50 = 0.84 ± 0.06 nM), while compound 5c showed the most efficient acetylcholinesterase inhibition (IC50 = 1.02± 0.65 μM). Docking predictions disclosed the docking poses of the synthesized molecules with all enzymes and demonstrated the outstanding potency of compounds 5a, 5f, and 5c (docking scores = −11.6, −15.3, and −14.0 kcal/mol against MAO-A, MAO-B, and AChE, respectively). These newly synthesized analogs act as up-and-coming candidates for the creation of safer curative use against Alzheimer’s illness.

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Pharmacophore studies of 1, 3, 4-oxadiazole nucleus: Lead compounds as α-glucosidase inhibitors

Cited by 13 publications

References 36 publications

Discovery of Potential Chemical Probe as Inhibitors of CXCL12 Using Ligand-Based Virtual Screening and Molecular Dynamic Simulation

Discovery of Potential Chemical Probe as Inhibitors of CXCL12 Using Ligand-Based Virtual Screening and Molecular Dynamic Simulation

Occurrence, Chemistry and Synthesis of Various Novel Methods of Oxadiazole

Synthesis and Evaluation of Novel S-alkyl Phthalimide- and S-benzyl-oxadiazole-quinoline Hybrids as Inhibitors of Monoamine Oxidase and Acetylcholinesterase

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