Design, Synthesis, In Silico Testing, and In Vitro Evaluation of Thiazolidinone-Based Benzothiazole Derivatives as Inhibitors of α-Amylase and α-Glucosidase

Abstract

In this study, a stepwise reaction afforded thiazolidinone-based benzothiazole derivatives 1–15, and the synthesized derivatives were then screened for biological significance and found to be the leading candidates against α-amylase and α-glucosidase enzymes. Almost all derivatives showed excellent to good activity ranging against α-amylase, IC50 = 2.10 ± 0.70 to 37.50 ± 0.70 μM, and α-glucosidase, IC50 = 3.20 ± 0.05 to 39.40 ± 0.80 μM. Some analogues such as 4 (2.40 ± 0.70 and 3.50 ± 0.70 μM), 5 (2.30 ± 0.05 and 4.80 ± 0.10 μM), and 6 (2.10 ± 0.70 and 3.20 ± 0.70 μM) were found with folds better activity than that of the standard drug acarbose (9.10 ± 0.10 and 10.70 ± 0.10 μM), respectively. Moreover, the structure–activity relationship (SAR) has been established for all compounds. A molecular docking study has been carried out to explore the binding interactions against α-amylase and α-glucosidase enzymes.

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

“…Indole-linked derivatives of thiazolidinone 31 a-t were synthesized and tested for their in vitro α-amylase and αglucosidase inhibitory potential by Khan and coauthors. [88] Tested analogs exhibited good to moderate potential, while compounds In another work, Khan and coauthors [89] synthesized benzothiazole clubbed thiazolidinone derivatives 32 a-o and evaluated them for antidiabetic potential using α-amylase and glucosidase enzymes. Compounds were found to show notice-able potency, while compounds 32 d (IC 50 = 2.40 and 3.50 μM), 32 e (IC 50 = 2.30 and 4.80 μM), and 32 f (IC 50 = 2.10 and 3.20 μM) were found more effective than reference, Acarbose (IC 50 = 9.10 and 10.70 μM).…”

“…In another work, Khan and coauthors [89] synthesized benzothiazole clubbed thiazolidinone derivatives 32 a – o and evaluated them for antidiabetic potential using α‐amylase and α‐glucosidase enzymes. Compounds were found to show noticeable potency, while compounds 32 d (IC 50 =2.40 and 3.50 μM), 32 e (IC 50 =2.30 and 4.80 μM), and 32 f (IC 50 =2.10 and 3.20 μM) were found more effective than reference, Acarbose (IC 50 =9.10 and 10.70 μM).…”

Semi-synthesis, α-amylase inhibition, and kinetic and molecular docking studies of arylidene-based sesquiterpene coumarins isolated from Ferula tunetana Pomel ex Batt

“…3,4 One of the main approaches to managing DM involves inhibiting the α-amylase enzyme, which is responsible for cleaving carbohydrates (starch and oligosaccharides) into small sugar units, ultimately leading to hyperglycemia and the subsequent development of diabetes. 5 In this regard, the inhibition of the α-amylase enzyme plays an important role in the treatment of diabetes. In fact, targeting α-amylase inhibitors with small molecules is one of the methods to find new antidiabetic drugs.…”

SPE–UPLC–MS/MS for Determination of 36 Monomers of Alkylphenol Ethoxylates in Tea

“…Gas chromatography (GC) and liquid chromatography (LC) are usually coupled to mass spectrometry to analyze APEOs [ 30 ]. Nevertheless, when APEOs contain more than five ethoxylation units, their volatility and thermal stability become poor, requiring derivatization for GC–MS analysis [ 33 ]. LC–MS/MS was developed to analyze APEOs, providing better selectivity and lower detection limits [ 34 ].…”