Current Status of Computer-Aided Drug Design for Type 2 Diabetes

Abstract

BackgroundDiabetes is a metabolic disorder that requires multiple therapeutic approaches. The pancreas loses its functionality to properly produce the insulin hormone in patients with diabetes mellitus. In 2012, more than one million people worldwide died as a result of diabetes, which was the eighth leading cause of death.ObjectiveMost drugs currently available and approved by the U.S. Food and Drug Administration cannot reach an adequate level of glycemic control in diabetic patients, and have many side effects; thus, new classes of compounds are required. Efforts based on computer-aided drug design (CADD) can mine a large number of databases to produce new and potent hits and minimize the requirement of time and dollars for new discoveries.MethodsPharmaceutical sciences have made progress with advances in drug design concepts. Virtual screening of large databases is most compatible with different computational methods such as molecular docking, pharmacophore, quantitative structure-activity relationship, and molecular dynamic simulation. Contribution of these methods in selection of antidiabetic compounds has been discussed.ResultsThe Computer-Aided Drug Design (CADD) approach has contributed to successful discovery of novel anti-diabetic agents. This mini-review focuses on CADD approach on currently approved drugs and new therapeutic agents-in-development that may achieve suitable glucose levels and decrease the risk of hypoglycemia, which is a major obstacle to glucose control and a special concern for therapies that increase insulin levels.ConclusionDrug design and development for type 2 diabetes have been actively studied. However, a large number of antidiabetic drugs are still in early stages of development. The conventional target- and structure-based approaches can be regarded as part of the efforts toward therapeutic mechanism-based drug design for treatment of type 2 diabetes. It is expected that further improvement in CADD approach will enhance the new discoveries.

An Integrated Computational Approach for Plant-Based Protein Tyrosine Phosphatase Non-Receptor Type 1 Inhibitors

“…We have discussed in our previous research that most of FDA approved anti-DM medicines now available cannot achieve a satisfactory level of glycemic control in DM patients, and have many side effects; therefore, new classes of anti-DM medicines are urgently needed. CADD techniques could be exploited to filter a large number of databases to produce efficient hits and to minimize the time and financial investments needed to discover novel anti-DM medications [ 6 ].…”

“…In our previous study, we discussed U.S. Food and Drug Administration (FDA) approved anti-DM medicines; insulin, biguanides, second generation sulfonylureas, alpha- glucosidase inhibitors, glinides, glucagon-like peptide-1 receptor agonists, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, bile acid sequestrants, dopamine agonists, amylin analogs, and sodium-dependent glucose cotransporter-2 inhibitors in detail [ 6 ]. However, currently available anti-DM drugs possess side effects such as headache, stomach upset, peripheral edema, increase in weight, and hypotension [ 7 ].…”

QSAR modelling and docking analysis of some thiazole analogues as alfa-glucosidase inhibitors

“…Thiazole and its derivatives have wide industrial application in pharmacy, liquid crystals, and polymers (de Souza, 2005). Thiazoles have several biological activities such as antioxidant, insecticidal, antitumor, anticonvulsant, anti-hyperlipidemic and antiinflammatory (Khan et al, 2016) Computer-aided drug design (CADD) is a unique area in drug discovery arena which apply the concept of molecular modelling to study the interaction between drugs and their target protein (Bibi and Sakata, 2016). QSAR is a molecular modeling technique widely used to correlate physicochemical properties of compounds and their experimentally determined activities (Alisi et al, 2018).…”

Molecular Modeling and Simulation of Transketolase from Orthosiphon stamineus

“…There are many drugs produced and available in the market in order to cure these diseases. Nevertheless, the drugs cannot reach the adequate level to control those diseases in patients and may cause side effects on patients in long term [1]. In recent years, computer-aided drug design became an alternative approach to produce drugs with higher effectiveness as it can accelerate new drug discovery and cheaper production.…”