New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro

Rafiq, Kashif; Khan, Majid; Muhammed, Niaz; Khan, Ajmal; Rehman, Najeeb Ur; Al-Yahyaei, Balqees Essa Mohammad; Khiat, Mohammed; Halim, Sobia Ahsan; Shah, Zarbad; Csük, René; Al‐Harrasi, Ahmed

doi:10.1007/s00044-020-02696-0

Cited by 24 publications

(8 citation statements)

References 58 publications

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“…The docking experiment was carried out on Molecular Operating Environment (MOE version 2020.0901) 29 . Previously, we have tested the docking performance of MOE through re-docking protocol and MOE showed good efficiency 5 , 7 , 29 , 30 . In this work, the protein file was prepared for docking by QuickPrep module of MOE which add missing hydrogens on each residue of protein to fulfil their valency and calculates partial charges (via Amber10: EHT force field).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Pasha

Khan

Ullah

et al. 2023

Sci Rep

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Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a–y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14–115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.

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Section: Resultsmentioning

confidence: 99%

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Pasha

Khan

Ullah

et al. 2023

Sci Rep

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“…The docking study of the active compounds was conducted in molecular operating environment [42] on the X-ray crystal structure of isomaltase from Saccharomyces cerevisiae in complex with alpha-D-glucopyranose (PDB code: 3A4A, resolution: 1.60 Å) [43]. In our previous studies [11,40,44], we have thoroughly checked the docking performance of applied docking protocol via re-docking of acarbose in the active site of α-glucosidase where MOE was found efficient with an RMSD value of 0.36 Å. The enzyme file was handled through QuickPrep module of MOE to add missing hydrogen atoms on each residue and to calculate partial charges using pre-defined force field (Amber10:EHT force field).…”

Section: Molecular Dockingmentioning

confidence: 99%

“…Due to their easy synthesis and active pharmacophore group (C=N moiety), hydrazones mostly display good biological and catalytic activities [2]. The Schiff base moiety is a valuable group which is found several bioactive compounds including antioxidant [3,4], antibacterial [5,6], anti-fungal, antiviral [6,7], anti-diabetic [2], anticancer [8], antitumor [9], xanthine oxidase and α-glucosidase inhibitors [10][11][12], antiinflammatory [13], and anti-convulsant molecules [14]. Khan et al synthesized and reported the flurbiprofen derivatives as novel α-amylase inhibitors [15], whereas studies have also shown the potent inhibitory potential of Schiff's bases for cyclooxygenase enzymes (COX-I and COX-II) [15,16].…”

Section: Introductionmentioning

confidence: 99%

Bio-Oriented Synthesis of Novel (S)-Flurbiprofen Clubbed Hydrazone Schiff’s Bases for Diabetic Management: In Vitro and In Silico Studies

et al. 2022

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A new series of (S)-flurbiprofen derivatives 4a–4p and 5a–5n were synthesized with different aromatic or aliphatic aldehydes and ketones to produce Schiff’s bases and their structures were confirmed through HR-ESI-MS, 1H, and 13C-NMR spectroscopy. The α-glucosidase inhibitory activities of the newly synthesized compounds were scrutinized, in which six compounds 5k, 4h, 5h, 4d, 4b, and 5i showed potent inhibition in the range of 0.93 to 10.26 µM, respectively, whereas fifteen compounds 4c, 4g, 4i, 4j, 4l, 4m, 4o, 4p, 5c, 5d, 5j, 5l, 5m, 5n and 1 exhibited significant inhibitory activity with IC50 in range of = 11.42 to 48.39 µM. In addition, compounds 5g, 5f, 4k, 4n, and 4f displayed moderate-to-low activities. The modes of binding of all the active compounds were determined through the molecular docking approach, which revealed that two residues, specifically Glu277 and His351 are important in the stabilization of the active compounds in the active site of α-glucosidase. Furthermore, these compounds block the active site with high binding energies (−7.51 to −3.36 kcal/mol) thereby inhibiting the function of the enzyme.

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“…are not selective causing the undesirable side effects. Recently we have investigated the interaction of CA-II isozymes with several types of natural and synthetic compounds [46,47,52,53]. Furthermore, 1,3,4-oxadiazole derivatives were found to be strong inhibitors against carbonic anhydrase II enzyme [39][40][41][42]44].…”

Section: Chemistrymentioning

confidence: 99%

“…with phenylalanine hydrazide (1, 0.5 mmol, 1 equiv.) in ethanol at refluxing temperature in 90% yield [52] (Scheme 2). The oxidative cyclization of 3a-l to 4a-l was achieved by utilizing molecular iodine in the presence of potassium carbonate (1.8 mmol, 3 equiv.)…”

Section: Chemistrymentioning

confidence: 99%

Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors

et al. 2022

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Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids (4a–l), characterized by 1H- and 13C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives 4a–l exhibited selective inhibition against CA-II. All the compounds (except 4d) exhibited good to moderate CA-II inhibitory activities with IC50 value in range of 12.1 to 53.6 µM. Among all the compounds, 4a (12.1 ± 0.86 µM), 4c (13.8 ± 0.64 µM), 4b (19.1 ± 0.88 µM) and 4h (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II.

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New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro

Cited by 24 publications

References 58 publications

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Bio-Oriented Synthesis of Novel (S)-Flurbiprofen Clubbed Hydrazone Schiff’s Bases for Diabetic Management: In Vitro and In Silico Studies

Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors

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