Isatin thiazoles as antidiabetic: Synthesis, in vitro enzyme inhibitory activities, kinetics, and in silico studies

Abstract

Diabetes mellitus is one of the most prevalent diseases nowadays. Several marketed drugs are available for the cure and treatment of diabetes, but there is still a dire need of introducing compatible drug molecules with lesser side effects. The current study is based on the synthesis of isatin thiazole derivatives 4-30 via the Hantzsch reaction. The synthetic compounds were characterized using different spectroscopic techniques and evaluated for their α-amylase and α-glucosidase inhibition potential.Of 27 isatin thiazoles, five (4, 5, 10, 12, and 16) displayed good activities against the α-amylase enzyme with IC 50 values in the range of 22.22 ± 0.02-27.01 ± 0.06 µM, and for α-glucosidase, the IC 50 values of these compounds were in the range of 20.76 ± 0.17-27.76 ± 0.17 µM, respectively. The binding interactions of the active molecules within the active site of enzymes were studied with the help of molecular docking studies. In addition, kinetic studies were carried out to examine the mechanism of action of the synthetic molecules as well. Compounds 3a, 4, 5, 10, 12, and 16 were also examined for their cytotoxic effect and were found to be noncytotoxic. Thus, several molecules were identified as good antihyperglycemic agents, which can be further modified to enhance inhibition ability and to find the lead molecule that can act as a potential antidiabetic agent.

Synthesis of Thiazole‐Chalcone Hybrid Molecules: Antioxidant, Alpha(α)‐Amylase Inhibition and Docking Studies

“…[32][33][34][35][36][37][38][39][40][41][42][43][44] The hydrazinylthiazoles have also potential for α-amylase, anti-glycation and antioxidant activity as shown in Figure 2. [45,46] Based on the biological significance of thiazole and in continuation of our work on this particular nucleus, in the quest for new drugs, to overcome drug resistance challenges, herein we switched to molecular hybrid approach. The current project was designed to combine the thiazole and chalcone scaffolds together where ring A of chalcone is replaced by thiazole (Figure 3).…”

“…Thiazole nucleus is the key to dealing with various biological disorders like microbial infections, [28–29] inflammations, [30] thyroid disorder, histaminic issues, [31] and various viral infections [32–44] . The hydrazinylthiazoles have also potential for α‐amylase, anti‐glycation and antioxidant activity as shown in Figure 2 [45,46] …”

Synthesis of Arylidenehydrazinyl‐4‐methoxyphenylthiazole Derivatives: Docking Studies, Probing Type II Diabetes Complication Management Agents

“…[15] Thiazole derivatives have been well documented as an important pharmacologically active class in treatment of diabetes. [12,[16][17][18][19][20][21] Several thiazole derivatives have been used to treat diabetes and its complications as summarised in Figure 1. [22] The potential of hydrazinyl-thiazole derivatives in managing diabetes via αamylase inhibition, [22] glycation inhibition and antioxidant action (Figure 1D), [23] led us to design and synthesize compounds 3a-o.…”

“…Thiazole derivatives have been well documented as an important pharmacologically active class in treatment of diabetes [12,16–21] . Several thiazole derivatives have been used to treat diabetes and its complications as summarised in Figure 1 [22] .…”

Discovery of 5-Methylthiazole-Thiazolidinone Conjugates as Potential Anti-Inflammatory Agents: Molecular Target Identification and In Silico Studies

“…Thiazole ring was found to possess a significant broad spectrum of pharmacological and pharmaceutical actions in the biological system. Among them are anti-inflammatory [ 17 , 18 , 19 , 20 ], antimicrobial [ 21 , 22 ], anticancer [ 23 , 24 , 25 ], anti-HIV [ 26 , 27 ], antioxidant [ 28 , 29 ], antidiabetic [ 30 , 31 ], local anesthetic [ 32 ] activities, among many others [ 28 , 33 , 34 ]. Furthermore, thiazole scaffold is present in some FDA-approved drugs, such as tiazofurin [ 35 ], an antineoplastic drug, vitamin B1 [ 36 ], ritonavir, an approved drug against HIV [ 37 ], meloxicam [ 38 ] NSAID and abafungin, a broad-spectrum antifungal agent with a novel mechanism of action for the treatment of dermatomycoses ( Figure 2 ).…”