Drug Design, Development and Therapy (Apr 2024)
Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives – Imidazoline Receptor Agonists
Abstract
Artur Martynov,1 Boris Farber,2 Tatyana Bomko,1 Daniel L Beckles,3 Ilya Kleyn4 1Laboratory and Clinical department of Molecular Immunopharmacology, SI “ I. Mechnikov Institute of Microbiology and Immunology of National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine; 2R&D Department, Noigel LLC, New York, NY, USA; 3Baylor Scott & White Health, Round Rock, TX, USA; 4SUNY Downstate Medical Center / University Hospital of Brooklyn, New York, NY, USACorrespondence: Artur Martynov, Email [email protected]: The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats.Methods: The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances.Results & Discussion: The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.Keywords: imidazoline receptors, benzimidazole derivatives, synthesis, antihyperglycemic activity
