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Today, the world of science is constantly challenged with new genomics, which in turn is responsible for new disease-causing targets. Hence, there is a need for developing drugs acting against such targets. Computational methods are proving to be a mainstay in the drug discovery process, mainly through virtual screening. This review discusses about the recent advancements in structure-based drug design with reference to Virtual Screening along with its procedures from ligand preparation and protein preparation, docking, scoring function, databases, and virtual (VS) algorithms. Application of Structure-based VS in combination with other virtual screening techniques has also been highlighted in this review. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a–5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents. [ABSTRACT FROM AUTHOR]

Aryloxypropanolmines have been reported to have β3-agonist activity. Agonists of β3-adrenergic receptors have been observed to simultaneously increase lipolysis, fat oxidation, energy expenditure and insulin action leading to the belief that this receptor might serve as an attractive target for the treatment of diabetes and obesity. Various aryloxypropanolamine derivatives have been synthesized starting with the substituted imines derived from 4-hydroxy benzaldehyde and substituted anilines. These imines have been converted to benzamide intermediates. The benzamide epoxide intermediates have been synthesized using epichlorhydrin. The title compounds 6a-j have been synthesized via ring opening of the epoxides. The synthesized compounds have been characterized using infrared (IR), nuclear magnetic resonance (NMR) and mass spectrometry. The synthesized compounds have been evaluated for antidiabetic activity on streptozotocin induced diabetic male Wistar rats. The synthesized aryloxypropanolamine derivative consisting of -OCH3 and t-butyl amine substituents show good activity as compared to the other synthesized compounds in the series. Glibenclamide has been taken as standard for measuring the antidiabetic activity. [ABSTRACT FROM AUTHOR]

Hybridization is an important strategy to design molecules that can be effectively used to treat fatal diseases known to mankind. Molecular hybrids and their pharmacological investigations aided in discovering several potent isatin (Indole 2, 3 dione) derivatives with anti-HIV, antimalarial, antitubercular, antibacterial, and anticancer activities. Indole-2,3-dione and their derivatives have diverse pharmacological properties and have a prominent role in the discovery of new drugs. To understand the various approaches for designing new molecules based on isatin nucleus analysis of various pharmacophore hybrids, spacers/linkers between pharmacophores and isatin for hybridization and their biological activities are important. This review discusses the progress in developing isatin hybrids as biologically effective agents and their crucial aspects of design and structure-activity relationships., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)