Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach
Abstract:Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4… Show more
“…[146] Their low IC 50 values proved them to be even better than the reference drug acarbose (IC 50 = 38. The same research group carried out the further expansion of research work, [74] to identify compounds 136 a-m and 137 am as potential targets which are synthesized by treating 22 a-b with 2-bromo-N-arylacetamides 135 a-m in presence of potassium carbonate in DMF (Scheme 20).…”
Section: Antidiabetic Activity Of 12-benzothiazine Derivativesmentioning
confidence: 99%
“…The remarkable features of these heterocycles can be witnessed by their large number of publications (1782) and citations (11592) in recent times. Here in this review, therapeutic applications of 1,2‐benzothiazines in the arena of anti‐inflammatory, [23–37] anticancer, [38–56] antimicrobial, [57–62] antioxidant, [56,58,63–66] antidiabetic, [67–74] nor‐A efflux pump inhibitor, [75] antiepileptic, [76] anti‐arthritis, [77] anti‐HIV‐1, [78–81] alkaline phosphate inhibitors, [82] anti‐monoamine oxidase, [83] anti‐11β‐hydroxysteroid dehydrogenase, [84–85] calpain‐1 inhibitors, [86–87] and hepatitis virus‐C [88–89] along with their corresponding synthesis have been visualized. The prominence attained by derivatives of thiazole [90–91] and thiazine [15,92] lead researchers to construct medications like alpelisib and prochlorperazine maleate and a lot more (Figure 1).…”
Benzothiazines are one of the significant nitrogen containing heterocyclic scaffolds which are found to be multipurpose in the fields of drug discovery and medicinal chemistry. They are realized to be effective in curing enzymatic diseases caused by COX-2, ALR-2 (Aldose reductase enzyme), ALP (Alkaline phosphatase), 11β-HSD 1 (11βhydroxysteroid dehydrogenase type 1) and proteolytic enzyme. These motifs act as a worthy candidate against cancerous cells, microorganisms, reactive oxygen species (ROS), viruses (HIV-1, HCV-NS5B) and monoamine oxidases. The objective of this review is to shed lime light on the medicinal and pharmacological aspects of 1,2-benzothiazine derivatives which have been discovered in recent times for the benefit of broad range of readers in chemistry fraternity [a
“…[146] Their low IC 50 values proved them to be even better than the reference drug acarbose (IC 50 = 38. The same research group carried out the further expansion of research work, [74] to identify compounds 136 a-m and 137 am as potential targets which are synthesized by treating 22 a-b with 2-bromo-N-arylacetamides 135 a-m in presence of potassium carbonate in DMF (Scheme 20).…”
Section: Antidiabetic Activity Of 12-benzothiazine Derivativesmentioning
confidence: 99%
“…The remarkable features of these heterocycles can be witnessed by their large number of publications (1782) and citations (11592) in recent times. Here in this review, therapeutic applications of 1,2‐benzothiazines in the arena of anti‐inflammatory, [23–37] anticancer, [38–56] antimicrobial, [57–62] antioxidant, [56,58,63–66] antidiabetic, [67–74] nor‐A efflux pump inhibitor, [75] antiepileptic, [76] anti‐arthritis, [77] anti‐HIV‐1, [78–81] alkaline phosphate inhibitors, [82] anti‐monoamine oxidase, [83] anti‐11β‐hydroxysteroid dehydrogenase, [84–85] calpain‐1 inhibitors, [86–87] and hepatitis virus‐C [88–89] along with their corresponding synthesis have been visualized. The prominence attained by derivatives of thiazole [90–91] and thiazine [15,92] lead researchers to construct medications like alpelisib and prochlorperazine maleate and a lot more (Figure 1).…”
Benzothiazines are one of the significant nitrogen containing heterocyclic scaffolds which are found to be multipurpose in the fields of drug discovery and medicinal chemistry. They are realized to be effective in curing enzymatic diseases caused by COX-2, ALR-2 (Aldose reductase enzyme), ALP (Alkaline phosphatase), 11β-HSD 1 (11βhydroxysteroid dehydrogenase type 1) and proteolytic enzyme. These motifs act as a worthy candidate against cancerous cells, microorganisms, reactive oxygen species (ROS), viruses (HIV-1, HCV-NS5B) and monoamine oxidases. The objective of this review is to shed lime light on the medicinal and pharmacological aspects of 1,2-benzothiazine derivatives which have been discovered in recent times for the benefit of broad range of readers in chemistry fraternity [a
“…The clinically available oral AGI drugs, acarbose, miglitol, and voglibose are therapeutic approaches to reduce the risk of T2DM. [6] These AGIs are associated with gastrointestinal adverse effects like stomach pain, diarrhoea, cramping, enhanced flatulence, and rectal bleeding. [7,8] The adverse effects of these drugs are forcing researchers to search a new, effective, and safer alternate molecules.…”
Section: Introductionmentioning
confidence: 99%
“…Thus, the identification of α ‐glucosidase inhibitors (AGIs) has sparked a lot of interest. The clinically available oral AGI drugs, acarbose, miglitol, and voglibose are therapeutic approaches to reduce the risk of T2DM [6] . These AGIs are associated with gastrointestinal adverse effects like stomach pain, diarrhoea, cramping, enhanced flatulence, and rectal bleeding [7,8] .…”
γ‐Butyrolactone (GBL) is a five‐membered heterocycle with an ester group that received much attention in drug development. They exhibit a broad range of biological activities like antiglaucoma, antibiotics, neuroprotective, antifungal, and diuretics, along with a few antidiabetic activities. Here, six GBL derivatives were synthesized via semi‐synthetic modification of naturally occurring acyclic monoterpene dihydrotagetone (DHT) isolated from the essential oil of Tagetes minuta. All GBL derivatives were screened for α‐glucosidase inhibitory (AGI) activity. Present studies demonstrated that ethyl substituted GBL derivative i. e., 5‐ethyl‐5‐isobutyl‐3‐methyldihydrofuran‐2(3H)‐one (IC50=5.88±0.21 μM) has the nearly similar α‐glucosidase inhibitory activity to the reference drug acarbose (IC50= 5.47±0.62 μM) while the DHT (IC50=15.32±1.44 μM) and its acid version i. e., 2,6‐dimethyl‐4‐oxoheptanoic acid (IC50=18.61±0.87 μM) has lowest inhibition activity in the same assay. Furthermore, molecular docking studies were conducted to explore binding interactions of the GBL derivatives with α‐glucosidase. This study discovered a new class of α‐glucosidase inhibitors.
“…Over the recent years, heterocyclic compounds have been extensively studied as α-glucosidase inhibitors [ 26 , 27 , 28 ]. More specifically, the benzimidazole ring system has emerged as an efficient template for new and potential anti-diabetic agents [ 29 , 30 , 31 ].…”
α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.
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