Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin –induced diabetic albino wistar rats

Taha, Muhammad; Imran, Syahrul; Salahuddin, M.; Iqbal, Naveed; Uddin, Nizam; Shehzad, Adeeb; Farooq, Rai Khalid; Alomari, Munther; Khan, Khalid Mohammed

doi:10.1016/j.bioorg.2021.104808

Cited by 23 publications

(5 citation statements)

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“…In this context, acarbose, miglitol, metformin, voglibose, etc. are currently the only clinically licensed medications that can be used as monotherapy or in conjunction with insulin or other oral medications in the treatment of type-2 diabetes. , When these medications are taken regularly, they might cause unpleasant gastrointestinal side effects such as diarrhea, abdominal bloating, pain, and flatulence. − Based on the biological importance of α-glucosidase and the inefficiencies of existing drugs, the development of new α-glucosidase inhibitors is still an interesting target in medicinal chemistry research. − …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2,3-Dihydro-1,5-Benzothiazepines as α-Glucosidase Inhibitors: In Vitro, In Vivo, Kinetic, SAR, Molecular Docking, and QSAR Studies

Mehmood¹,

Mughal

Obaid

et al. 2022

ACS Omega

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In the present study, a series of 2,3-dihydro-1,5-benzothiazepine derivatives 1B – 14B has been synthesized sand characterized by various spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using in vitro and in vivo mechanism-based assays. The tested compounds 1B – 14B exhibited in vitro inhibitory potential against α-glucosidase with IC 50 = 2.62 ± 0.16 to 10.11 ± 0.32 μM as compared to the standard drug acarbose (IC 50 = 37.38 ± 1.37 μM). Kinetic studies of the most active derivatives 2B and 3B illustrated competitive inhibitions. Based on the α-glucosidase inhibitory effect, the compounds 2B , 3B , 6B , 7B , 12B , 13B , and 14B were chosen in vivo for further evaluation of antidiabetic activity in streptozotocin-induced diabetic Wistar rats. All these evaluated compounds demonstrated significant antidiabetic activity and were found to be nontoxic in nature. Moreover, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of the α-glucosidase enzyme (PDB ID 3AJ7 ). Additionally, quantitative structure–activity relationship (QSAR) studies were performed based on the α-glucosidase inhibitory assay. The value of correlation coefficient ( r ) 0.9553 shows that there was a good correlation between the 1B – 14B structures and selected properties. There is a correlation between the experimental and theoretical results. Thus, these novel compounds could serve as potential candidates to become leads for the development of new drugs provoking an anti-hyperglycemic effect.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2,3-Dihydro-1,5-Benzothiazepines as α-Glucosidase Inhibitors: In Vitro, In Vivo, Kinetic, SAR, Molecular Docking, and QSAR Studies

Mehmood¹,

Mughal

Obaid

et al. 2022

ACS Omega

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“…Here, ligand binding of the residues is conventional hydrogen bonds as ASP B:92 1.84 Å, ARG B:227 2.19 Å, TYR B:207 1.82 and LYS B: 168 5.23 Å, TYR B:134 2.68 Å, GLU B: 203 2.28 Å, and 2.96 Å carbon‐hydrogen bonds and finally van der Waals bonds such as ALA B:170, TRP B:47. The results showed that the protein binding algorithm was reasonable (Taha et al., 2021).…”

Section: Resultsmentioning

confidence: 99%

“…Molecular docking, drug‐like profiling, and kinetic analysis were performed to better illustrate the mechanism of inhibition of the compounds by the AChE enzyme (Taha et al., 2021). Chrysin and chlorogenic acid were used as the most active compound selected and its binding to the AChE enzyme was performed.…”

Section: Resultsmentioning

confidence: 99%

The effects of Daucus carota extract against PC3, PNT1a prostate cells, acetylcholinesterase, glutathione S‐transferase, and α‐glycosidase; an in vitro–in silico study

et al. 2021

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Daucus carota L. ssp. major (DCM) plant is widely used in traditional medicine to treat some types of cancer and various diseases. Therefore, we evaluated the biological activities of this plant to define its effects against prostate cancer (PCa), Alzheimer’s disease (AD), oxidation, and diabetes mellitus (DM) as well as identified its phenolic composition. To determine the anti‐cancer properties of the plant extract, we treated PCa cells with the extract at a concentration range of 0.25, 0.5, 1, 2, and 4 mg/ml. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. As a result of precise measurements at the millimolar level, it was observed that the plant extract showed an effective inhibition (IC50) against glutathione S‐transferase (GST; 12.84 mM), acetyl cholinesterase (AChE; 15.07 mM), and α‐Gly (11.75 mM) enzymes when compared with standard inhibitors. Antioxidant activities of DCM methanol extract were determined via two well‐known in vitro techniques. The extracts showed antioxidant activities against the DPPH and ABTS+. The LC‐ESI‐MS/MS was used to determine the phenolic compounds of methanol extract from DCM. Chlorogenic acid (2,089.096 µg/g), shikimic acid (193.14 µg/g), and coumarin (113.604 µg/g) were characterized as major phenolic compounds. In addition, the interactions of chlorogenic acid, chrysin, coumarin, and shikimic acid with the used three enzymes have been calculated using molecular docking simulation. Practical applications Plant natural phenolic compounds have protective effects such as anti‐inflammatory, antioxidant, anticarcinogen, and enzyme inhibitory. Therefore, it has an important place in the food and pharmaceutical industry. The present study aims to reveal the enzyme inhibitory, antioxidant, and anticarcinogenic properties of the Daucus carota ssp. Major (DCM) plant extract. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. DCM extract demonstrated considerable antioxidant activity and inhibitory potential on used metabolic enzymes. These biological effects are thought to have a relationship with rich chemical composition.

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“…With the current variety of antimicrobial drugs, sulfonamides [ 7 , 8 , 9 ], which are used in medicine [ 10 , 11 , 12 , 13 ] and veterinary medicine, still play an important role in the fight against and prevention of various types of infections, having antibacterial, hypoglycemic and other types of biological activity. Despite the diverse number of new antibacterial agents, sulfonamides are regularly prescribed for the treatment of various infectious diseases, type 2 diabetes mellitus [ 7 , 14 , 15 , 16 , 17 ] and urinary tract infections [ 18 ] and for first aid, using napkins from hemostatic collagen plates in combination with zeolite powder and antibacterial drugs [ 19 ]. Typical representatives of sulfonamides are sulfanilamide, sulfacyl sodium, urosulfan, sulgin, norsulfazol, phthalazol, etazol, sulfadimezin, sulfapyridazine, sulfamonomethoxine, sulfadimethoxine, sulfalene and saladosin.…”

Section: Introductionmentioning

confidence: 99%

Nature of Luminescence and Pharmacological Activity of Sulfaguanidine

et al. 2023

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Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.

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Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin –induced diabetic albino wistar rats

Cited by 23 publications

References 44 publications

Synthesis of Novel 2,3-Dihydro-1,5-Benzothiazepines as α-Glucosidase Inhibitors: In Vitro, In Vivo, Kinetic, SAR, Molecular Docking, and QSAR Studies

Synthesis of Novel 2,3-Dihydro-1,5-Benzothiazepines as α-Glucosidase Inhibitors: In Vitro, In Vivo, Kinetic, SAR, Molecular Docking, and QSAR Studies

The effects of Daucus carota extract against PC3, PNT1a prostate cells, acetylcholinesterase, glutathione S‐transferase, and α‐glycosidase; an in vitro–in silico study

Nature of Luminescence and Pharmacological Activity of Sulfaguanidine

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