Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors

Khalaf, Reema Abu; Awad, Maha; Al‐Essa, Luay Y.; Mefleh, Sara; Sabbah, Dima A.; Al‐Shalabi, Eveen; Shabeeb, Ihsan

doi:10.1007/s11030-021-10253-z

Cited by 4 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, saxagliptin was also bound to the same binding site, yet with lower binding efficiency compared to the O. tenuiflorum phytoconstituents. The binding of O. tenuiflorum compounds to the inhibitor binding site of the protein also resembled the docking results obtained in a previous study [38], where synthesized Schiff's based compounds were docked into the inhibitor binding site of the DPP4 protein structure. The compounds were also evaluated in vitro, and were found with favorable results.…”

Section: Discussionsupporting

confidence: 81%

Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches

et al. 2022

View full text Add to dashboard Cite

Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of Ocimum tenuiflorum phytocompounds against DPP4. In this regard, three phytocompounds (1S-α-pinene, β-pinene, and dehydro-p-cymene) from O. tenuiflorum have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-p-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future.

show abstract

Section: Discussionsupporting

confidence: 81%

Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Schiff bases found applications in catalysis [ 24 ] and material science [ 25 ]. Furthermore, Schiff bases and their metal complexes are excellent pharmacophore [ 26 – 29 ] such as antibacterial, antifungal, antiviral, antimalarial, antiinflammatory, antioxidant, anticancer, cytotoxic, enzyme inhibitory therapeutics and including anti-COVID-19 [ 30 – 37 ]. Especially, Schiff bases derived from biologically active starting materials namely isatin [ 30 ], 2-azetidinone [ 31 ], cephalothin [ 32 ], and dopamine [ 13 – 16 ] showed interesting biological activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, structural characterization, and evaluation of new peptidomimetic Schiff bases as potential antithrombotic agents

et al. 2022

View full text Add to dashboard Cite

New Schiff bases functionalized with amide and phenolic groups synthesized by the condensation of 2-hydroxybenzaldehyde and 2-hydroxyacetophenone with amino acid amides which in turn were prepared in two steps from N -Boc-amino acids and homoveraltrylamine through intermediate compounds N -Boc-amino acids amides. The compounds were characterized by elemental analysis, FT-IR, UV–Vis, and NMR spectroscopy. The crystal structures of three Schiff bases were determined by single crystal X-ray diffraction. There exists O–H N, N–H O, and C–H O types of hydrogen bonds and C–H secondary bonding interactions in these crystalline solids. The Schiff bases have been screened for anticoagulant and antiplatelet aggregation activities. All the compounds showed procoagulant activity which shortens the clotting time of citrated human plasma in both platelet-rich plasma and platelet-poor plasma except the derivatives of L-methionine which showed anticoagulant activity by prolonging the clotting time. In addition, the compounds derived from benzyl cysteine and phenylalanine showed adenosine diphosphate induced antiplatelet aggregation activity, whereas others did not show any role. Moreover, all these compounds revealed non-hemolytic activity with red blood cells. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00706-022-02936-6.

show abstract

Novel Mn(II) and Cu(II) metal complexes with sulfa drug-derived ligands as potent antimicrobial and anticancer agents: In vitro studies, ADMET profile and molecular docking

Bourouai,

Bouchoucha,

Si Larbi

et al. 2024

Polyhedron

View full text Add to dashboard Cite

Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors

Cited by 4 publications

References 35 publications

Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches

Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches

Synthesis, structural characterization, and evaluation of new peptidomimetic Schiff bases as potential antithrombotic agents

Novel Mn(II) and Cu(II) metal complexes with sulfa drug-derived ligands as potent antimicrobial and anticancer agents: In vitro studies, ADMET profile and molecular docking

Contact Info

Product

Resources

About