Identification of benzothiazole‐rhodanine derivatives as α‐amylase and α‐glucosidase inhibitors: Design, synthesis, in silico, and in vitro analysis

Abstract

A novel series of benzothiazole-rhodanine derivatives (A1-A10) were designed and synthesized, with the aim of developing possible antidiabetic agents and the spectral characterization of these compounds was done using infrared spectroscopy (IR), proton-nuclear magnetic resonance ( 1 H-NMR), carbon-nuclear magnetic resonance (C 13 -NMR), and high resolution mass spectroscopy (HR-MS) techniques. In vitro hypoglycemic potential of the compounds was evaluated by performing α-amylase and α-glucosidase enzyme inhibitory assays. In addition, these compounds were subjected to in silico analysis. Based on the results, compounds A5, A6, and A9 displayed good activity in comparison with the standard acarbose. Based on Lineweaver-Burk plots, it was concluded that compounds A5 and A9 displayed competitive type of enzyme inhibition. Molecular dynamic simulations were conducted to evaluate the stability of the ligand-protein complex by the calculation of the root mean square deviation, root means square fluctuation, and solvent accessible surface area.diabetes mellitus, in silico analysis, molecular dynamics, pharmacophore, rhodanines | INTRODUCTIONDiabetes mellitus (DM) is a chronic metabolic disorder that causes a significant challenge for the healthcare system across the globe. Such a high prevalence of diabetes has boosted the search for novel alternatives. Owing to high blood glucose in diabetes, a series of complications such as blindness, high blood pressure, kidney, and stroke disorders may result. 1 Diabetes was anticipated to affect 415 million people in 2015, with type 2 diabetes (T2DM) accounting for more than 90% of cases, with the number expected to rise to 642 million by 2040. For controlling glycemia, there has been a development of a few synthetic drugs such as acarbose, metformin, and sitagliptin. However, many side effects have been resulted due to the consumption of these drugs, such as flatulence, diarrhea, and hypoglycemia. It is well-known that postprandial hyperglycemia is an important contributing factor to the progression of T2DM, therefore, postprandial management of hyperglycemia is one of the therapeutic approaches to combating T2DM diabetes. α-amylase and α-glucosidase are the two main carbohydrate digestive enzymes associated with postprandial hyperglycemia in T2DM patients. The alpha-1, 4-glycosidic bond

Recent Studies of Nitrogen and Sulfur Containing Heterocyclic Analogues as Novel Antidiabetic Agents: A Review

“…determined that compounds containing rhodanine benzothiazole are α‐amylase and α‐glucosidase inhibitors. Due to the electron‐donating group (OH) positioned at position‐4, compound 45 has strong inhibitory effects on α‐glucosidase and α‐amylase activity with IC 50 : 24.61±1.76 μM and 24.64±2.10 μM respectively [53] …”

“…Due to the electron-donating group (OH) positioned at position-4, compound 45 has strong inhibitory effects on α-glucosidase and α-amylase activity with IC 50 : 24.61 � 1.76 μM and 24.64 � 2.10 μM respectively. [53] Patil Ser497, and Ser505. [54] RB C et al identified rhodanine benzothiazole compounds as α-amylase and α-glucosidase inhibitors.…”

α‐Amylase Inhibitors Based on Thiazolidinone Skeleton: A Promising Approach in Diabetes Management

“…Benzothiazole clubbed derivatives of rhodanine 25 a – j were synthesized by Srinivasa and coauthors [82] and evaluated for their antidiabetic potential against α‐amylase and α‐glucosidase enzymes. Compounds 25 e and 25 i displayed comparable inhibitory potential with IC 50 =24.22 and 24.64 μM, respectively, against α‐amylase enzyme with standard Acarbose (IC 50 =24.35 μM), whereas with α‐glucosidase, compounds 25 g and 25 i displayed significant inhibition with IC 50 =24.74 and 24.61 μM, respectively.…”

Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease

“…In case of analog 5 and 6, interactions were found such as vander Waals, conventional hydrogen bond, Pi-anion, Pi-Sigma, alkyl, Pi-alkyl, salt bridge, halogen, Pi-sulphur, etc. The further detail of docking study were summarized as in our previous articles [ 30 , 31 , 32 , 33 , 34 , 35 ] and the assay protocols of both the activities have been added in Supplementary file [ 36 , 37 ].…”