# _applied sciences_
## 1 Introduction  
Type 2 diabetes, marked by persistent hyperglycemia, is tied to obesity, insulin resistance, and systemic inflammation (metaflammation) that damages beta cells in the pancreas [1]. The disease contributes significantly to the prevalence of non-communicable diseases globally. Managing it often involves inhibiting \(\alpha\)-glucosidase, an enzyme that helps convert complex carbohydrates into glucose. Existing pharmaceutical inhibitors, including acarbose and miglitol, help lower post-meal glucose levels but have drawbacks. They can be contraindicated for patients with gastrointestinal disorders and may not effectively control blood sugar levels. Thus, the pursuit of new compounds to act as \(\alpha\)-glucosidase inhibitors for diseases like type 2 diabetes is critical [2]. They could potentially enhance glycemic control, decrease long-term complications, and improve overall disease management [3].  
Currently, a large number of discoveries in the field of inhibitors are devoted to the synthesis of \(N\)-heterocyclic compounds. Benzimidazoles, thiadiazoles, thiazole, and triazoles are recommended as good inhibitors of \(\alpha\)-glucosidase, acetylcholine, and butyrylcholinesteraseerase [4; 5; 6; 7]. Among the various classes of compounds obtained from natural resources, triterpenoids also show potent antidiabetic activity, including \(\alpha\)-glucosidase-inhibiting effects [8; 9; 10; 11]. For example, oleanolic acid (OA) derivatives, such as oxime esters, showed inhibitory activities against \(\alpha\)-glucosidase and \(\alpha\)-amylase [12], a series ofbenzylidene derivatives exhibited excellent to moderate inhibitory effects, and inhibition kinetics results showed that the leading analogs were reversible and mixed-type inhibitors of \(\alpha\)-glucosidase and \(\alpha\)-amylase [13; 14]. OA indole derivatives with various electron-withdrawing groups possessed anti-\(\alpha\)-glucosidase activities and demonstrated the capacity to form ligand-enzyme complexes with \(\alpha\)-glucosidase enzymes [15]. However, in the field of metabolic disorders, researchers have not achieved such progress as with CDDO (an OA derivative), a potent anticancer agent which was evaluated in phase I clinical trials for the treatment of advanced solid tumors and lymphoma via the activation of Nrf2 in peripheral blood mononuclear cells and the inhibition of NF-\(\kappa\)B and cyclin D1 in tumor biopsies [16]. All this proves that oleanolic acid is a promising scaffold for obtaining new pharmacological agents, and the search for new inhibitors based on it remains an urgent and priority task.  
Keeping in mind the importance of these types of compounds, in this study, oleanolic acid derivatives containing nicotinic, isonicotinic, methoxycinnamic, succinic, polyamines, amides, arylidene, propargylaminoalkyl, and azepano fragments were synthesized, and their potencies as antidiabetic agents were investigated. It was found that the majority of the compounds exhibit significant \(\alpha\)-glucosidase-inhibiting properties. The \(N\)-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide with the most potential, obtained via a one-pot Cu (I)-catalyzed Mannich reaction, was the most active compound acting as a noncompetitive inhibitor, with a Ki (the dissociation constant of the enzyme-inhibitor complex) value estimated at 3.01 uM. The leading compound demonstrated that it can prevent inflammatory responses and the generation of ROS in immune cells and act synergistically with acarbose to ameliorate hyperglycemia. This exploration can provide alternative therapies while fostering a better understanding of immunometabolic disorders, thereby paving the path for targeted and potent treatments.