Impact of Molecular Symmetry/Asymmetry on Insulin-Sensitizing Treatments for Type 2 Diabetes

Abstract

Although the advantages and disadvantages of asymmetrical thiazolidinediones as insulin-sensitizers have been well-studied, the relevance of symmetry and asymmetry for thiazolidinediones and biguanides has scarcely been explored. Regarding symmetrical molecules, only one thiazolidinedione and no biguanides have been evaluated and proposed as an antihyperglycemic agent for treating type 2 diabetes. Since molecular structure defines physicochemical, pharmacological, and toxicological properties, it is important to gain greater insights into poorly investigated patterns. For example, compounds with intrinsic antioxidant properties commonly have low toxicity. Additionally, the molecular symmetry and asymmetry of ligands are each associated with affinity for certain types of receptors. An advantageous response obtained in one therapeutic application may imply a poor or even adverse effect in another. Within the context of general patterns, each compound must be assessed individually. The current review aimed to summarize the available evidence for the advantages and disadvantages of utilizing symmetrical and asymmetrical thiazolidinediones and biguanides as insulin sensitizers in patients with type 2 diabetes. Other applications of these same compounds are also examined as well as the various uses of additional symmetrical molecules. More research is needed to exploit the potential of symmetrical molecules as insulin sensitizers.

Natural Compounds as DPP-4 Inhibitors: 3D-Similarity Search, ADME Toxicity, and Molecular Docking Approaches

“…Visual analysis of each docked NP revealed that all poses are located within the DPP-4 receptor-binding cavity. The high affinity for a receptor is conditioned by the number of rotatable bonds (RBN), the polarity, and the length of the ligand [72]. The selected NPs, with the best CG4 docking scores, displayed the same or greater RBN except for ZINC524732009, a similar length/size, and lower polarity than diabetes-approved drugs (Table 1), which could favor a longer interaction with the receptor.…”