Design, synthesis, docking and biological evaluation of chalcones as promising antidiabetic agents. 2020

Aluru Rammohan, and Baki Vijaya Bhaskar, and Nagam Venkateswarlu, and Wei Gu, and Grigory V Zyryanov
Department of Organic and Biomolecular Chemistry, Ural Federal University, 19 Mira, Yekaterinburg 620002, Russian Federation; Natural Products Division, Department of Chemistry, Sri Venkateswara University, Tirupati, India. Electronic address: rammohan4ever@gmail.com.

Diabetes mellitus (DM) is a serious chronic metabolic disorder which occurs due to dysfunction of insulin and therapeutic approaches are poor. It is an under estimation that 387 million people currently suffering globally with diabetic and more than 592 million people may be affected by 2030. It makes an urgent necessity to discover novel drugs to control amplified diabetic populations. In this study, amino chalcones (3a-j) were synthesized and hydroxy chalcones (3g-j) were isolated from natural source such as Sophora interrupta, Clerodendrum phlomidis and Andrographis macrobotrys. Structural elucidation was carried out using Mass, 1H and 13C NMR Spectra. In vivo studies were carried out with alloxan induced diabetic rats (100 mg/kg) which reveals compounds 3c, 3a and 3h have significant antidiabetic efficacy with decreased blood glucose levels in the diabetic rats while compared with control rats. Besides, docking studies with aldose reductase, dipeptidyl peptidase, PPAR and glucosidase were monitored which accomplishes that the compounds 3c, 3i, 3a and 3d have eloquent binding affinity (kcal/mol) with aldose reductase, besides the chalcones 3c, 3b, 3d, 3e and 3i were also showed inhibition with DPP-IV, PPAR-α and α-glucosidase. Also, these compounds explicated distinct interactions i.e., π-π, π-cationic, polar, electrostatic and hydrophobic bonds were observed with key residues of binding pockets. Bioavailability is disclosed with Lipinski rule of five and the design pharmacokinetic as well as pharmacodynamic properties are reliable. Therefore, chalcones were implied as antidiabetic leads for in further studies and could be worthwhile for the development of new classes of effective antidiabetic agents.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D047188 Chalcones Derivatives of CHALCONE that are important intermediates in the formation of FLAVONOIDS with anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. 1,3-Diphenyl-propanediones,1,3-Diphenyl-propenones,1,3-Diphenylpropanediones,1,3-Diphenylpropenones,Chalconoids,1,3 Diphenyl propanediones,1,3 Diphenyl propenones,1,3 Diphenylpropanediones,1,3 Diphenylpropenones
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

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