Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors

Pogaku, Vinay; Gangarapu, Kiran; Basavoju, Srinivas; Tatapudi, Kiran Kumar; Katragadda, Suresh

doi:10.1016/j.bioorg.2019.103307

Cited by 69 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Scientists are more interested in estimating the drug-likeness properties that are bioavailability, pharmacokinetics (how body responds to the drug), pharmacodynamics (how drug acts on the body), solubility, toxicity, lipophilicity, permeability, logP, logD, kinetic and thermodynamic solubility, the volume of distribution, and biotransformation [24]. The underlying goal and end-game for all ADME studies are to better understand a compound's metabolite-mediated toxicity and safety profile to make a concrete decision on whether the compound can progress to late-stage preclinical and clinical studies to enable filing for an investigational new drug, new drug agreement, or a biologics licensing agreement.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Absorption, Distribution, Metabolism, and Excretion Activity of the Components of Madhuca Longifolia and Its Inhibiting Target Molecule

Panchal

Ankitha

et al. 2020

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objectives: Madhuca longifolia is a versatile tropical tree mostly cultivated or harvested in the wild in South Asia for its edible flowers and oil seeds. Mahua trees are vegetatively propagated; they act as soil improvers, and also help in soil reclamation and erosion control. M. longifolia is a plant of great importance due to its scientifically proven uses such as antioxidant activity, immune suppression, and neuroprotective activity, which is because of the various chemical constituents present in different parts of the plant. The aim of our study is to analyze the absorption, distribution, metabolism, and excretion (ADME) properties and pathways analysis of active components of M. longifolia. Methods: The detailed study of these chemical constituents is done using PubChem and software’s such as Rasmol and Pymol. Swiss ADME was used to find out the ADME properties of the chemical constituents present in the plant. The pathway analysis was done using a literature survey and Swiss TargetPrediction. Results: The research has identify the potentially active compound from the plant with its inhibitory target protein. Conclusion: The ADME result demonstrates the potential pharmacological activity of the plant compound, which can be studied through in vivo model against its potential inhibitory target molecules.

show abstract

Section: Discussionmentioning

confidence: 99%

Prediction of Absorption, Distribution, Metabolism, and Excretion Activity of the Components of Madhuca Longifolia and Its Inhibiting Target Molecule

Panchal

Ankitha

et al. 2020

Asian J Pharm Clin Res

View full text Add to dashboard Cite

show abstract

“…[13] Pogaku and coworkers synthesized new derivatives of triazolopyrimidine, which revealed α-glucosidase inhibitor activity. [14] In addition, the presence of fluoride atom on the skeleton of heterocyclic drugs improves their activity. [15,16] Recently, the widespread of COVID-19, caused by the new coronavirus 2 (SARS-CoV-2), all over the world has emerged as a serious concern to public health.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of antimicrobial azoloazines and molecular docking for inhibitingCOVID‐19

Muhammad

Farghaly

Althagafi

et al. 2021

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol.The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds 4, 5, 17a,b, 19, and 25 against the pathogenic fungal strains used; Aspergillus flavus and Candida albicans compared to ketoconazole. In addition, compounds 4, 5, 19, and 25 showed moderate antibacterial activities against most tested bacterial strains.Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of Candida albicans, suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.

show abstract

“…Due to the sugar-based structure of mentioned α-glucosidase inhibitors, their synthesis needs complicated multistep procedures 6 . Unfortunately, administration of these inhibitors is associated with undesirable side effects including diarrhea, abdominal discomfort, and atulence 7,8 . Thus, it would be essential to develop novel, safe, and e cient α-glucosidase inhibitors as an effective lead candidate for future antidiabetic drug discovery initiatives.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel pyrazole-benzofuran hybrids: in vitro α-glucosidase inhibitory activity, kinetic and molecular modeling study

Azimi¹,

Azizian²,

Najafi

et al. 2021

Preprint

View full text Add to dashboard Cite

In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 µM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 µM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.

show abstract

Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors

Cited by 69 publications

References 30 publications

Prediction of Absorption, Distribution, Metabolism, and Excretion Activity of the Components of Madhuca Longifolia and Its Inhibiting Target Molecule

Prediction of Absorption, Distribution, Metabolism, and Excretion Activity of the Components of Madhuca Longifolia and Its Inhibiting Target Molecule

Synthesis of antimicrobial azoloazines and molecular docking for inhibitingCOVID‐19

Design and synthesis of novel pyrazole-benzofuran hybrids: in vitro α-glucosidase inhibitory activity, kinetic and molecular modeling study

Contact Info

Product

Resources

About