scholarly journals New Carbonic Anhydrase-II Inhibitors from Marine Macro Brown Alga Dictyopteris hoytii Supported by In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7074
Author(s):  
Kashif Rafiq ◽  
Ajmal Khan ◽  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Majid Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
2D Nmr ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Binding Behavior ◽  
In Silico Studies ◽  
Ic50 Values ◽  
First Time

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds (1–12) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate (3), dimethyl 2,6-dibromoterepthalate (4), and (E)-3-(4-(dimethoxymethyl)phenyl) acrylic acid (5) are isolated for the first time as a natural product, while the rest of the compounds (1, 2, 6–12) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1H, 13C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds (13–20) previously isolated by our group from the same source along with the currently isolated compounds (1–12) were screened against the CA-II enzyme. All compounds, except 6, 8, 14, and 17, were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds (1, 4, 5, 7, 9, 10, 12, 13, 15, 18, and 19) exhibited significant inhibitory activity against CA-II with IC50 values ranging from 13.4 to 71.6 μM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

scholarly journals New Synthetic 1H-1,2,3-Triazole Derivatives of 3-O-Acetyl-β-boswellic Acid and 3-O-acetyl-11-keto-β-boswellic Acid from Boswellia Sacra Inhibits Carbonic Anhydrase II in Vitro

2020 ◽  
Author(s):  
Satya Avula ◽  
Najeeb Ur Rehman ◽  
Majid Khan ◽  
Sobia Ahsan Halim ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
2D Nmr ◽  
Docking Studies ◽  
Biologically Active ◽  
Carbonic Anhydrase Ii ◽  
Boswellic Acid ◽  
Allosteric Site ◽  
Active Compounds ◽  
Boswellic Acids

Abstract Boswellic acids are genus specific to Boswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl-β-boswellic acid (ABA, 1) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 2) derivatives (10a-d and 11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. All compounds were characterized by 1H NMR, 13C NMR, 2D NMR (HMBC, HSQC, COSY and NOESY) experiments, ESI-MS, and when applicable by 19F NMR spectroscopy (10b, 10c and 11b, 11c). This series has displayed a moderate to strong inhibition against CA II with IC50 values of 13.2–60.1 µM. All the active compounds were reported for the first time for their CA II inhibition potential. Kinetics studies on the most active inhibitors (5 and 10b) were carried out to investigate their mode of inhibition and to determine their inhibition constants Ki. Both compounds (5 and 10b) were found to be non-competitive inhibitors with Ki values of 10.40 ± 0.013 and 14.25 ± 0.017 µM, respectively. Molecular docking studies showed that all compounds were well accommodated in the allosteric site of CA II. The current study has demonstrated the usefulness of incorporating a 1H-1,2,3-triazole moiety into the boswellic acids skeleton.

scholarly journals New synthetic 1H-1,2,3-triazole derivatives of 3-O-acetyl-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid from Boswellia sacra inhibits carbonic anhydrase II in vitro

2021 ◽  
Author(s):  
Satya Kumar Avula ◽  
Najeeb Rehman ◽  
Majid Khan ◽  
Sobia Ahsan Halim ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
2D Nmr ◽  
Docking Studies ◽  
Biologically Active ◽  
Carbonic Anhydrase Ii ◽  
Boswellic Acid ◽  
Allosteric Site ◽  
Active Compounds ◽  
Boswellic Acids

Abstract Boswellic acids are genus specific to Boswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl-β-boswellic acid (ABA, 1) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 2) derivatives (10a-d and 11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. All compounds were characterized by 1H NMR, 13C NMR, 2D NMR (HMBC, HSQC, COSY and NOESY) experiments, ESI-MS, and when applicable by 19F NMR spectroscopy (10b, 10c and 11b, 11c). This series has displayed a moderate to strong inhibition against CA II with IC50 values of 13.2–60.1 µM. All the active compounds were reported for the first time for their CA II inhibition potential. Kinetics studies on the most active inhibitors (5 and 10b) were carried out to investigate their mode of inhibition and to determine their inhibition constants Ki. Both compounds (5 and 10b) were found to be non-competitive inhibitors with Ki values of 10.40 ± 0.013 and 14.25 ± 0.017 µM, respectively. Molecular docking studies showed that all compounds were well accommodated in the allosteric site of CA II. The current study has demonstrated the usefulness of incorporating a 1H-1,2,3-triazole moiety into the boswellic acids skeleton.

Inhibition Profiling of Urease and Carbonic Anhydrase II by High- Throughput Screening and Molecular Docking Studies of Structurally Diverse Organic Compounds

2020 ◽  
Vol 17 ◽  
Author(s):  
Majid Ali ◽  
Syed Majid Bukhari ◽  
Asma Zaidi ◽  
Farhan A. Khan ◽  
Umer Rashid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Metal Complexes ◽  
Organic Compounds ◽  
High Throughput ◽  
High Throughput Screening ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Molecular Docking Studies ◽  
Ic50 Values

Background:: Structurally diverse organic compounds and available drugs were screened against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening. Objective: The study was conducted to find out potential inhibitors of urease and carbonic anhydrase II. Methods:: Quantification of the possible HITs was carried out by determining their IC50 values. Results and Discussion:: of several screened compounds including derivatives of oxadiazole, coumarins, chromane-2, 4- diones and metal complexes of cysteine-omeprazole showed promising inhibitory activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active compounds with active sites of enzymes were investigated through molecular docking studies which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine possessing IC50 of 47 μM, interacts with one of the nickel metal atom of urease besides further interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409 along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values. Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II. Conclusion:: Among all the screened compounds, highly active inhibitor of carbonic anhydrase II was (4-(3- hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of carbonic anhydrase II through hydroxyl group of phenyl ring.

scholarly journals Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1694
Author(s):  
Kamel Arraki ◽  
Perle Totoson ◽  
Alain Decendit ◽  
Andy Zedet ◽  
Justine Maroilley ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Methanolic Extract ◽  
Significant Inhibition ◽  
Isolation And Identification ◽  
Vasorelaxant Effect ◽  
Methanolic Extracts ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
First Time

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.

scholarly journals Dual inhibitors of urease and carbonic anhydrase-II from Iris species

2019 ◽  
Vol 91 (10) ◽  
pp. 1695-1707 ◽  
Author(s):  
Muhammad Saleem ◽  
Sumaira Hareem ◽  
Ajmal Khan ◽  
Suad Naheed ◽  
Muslim Raza ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Significant Inhibition ◽  
Carbonic Anhydrase Ii ◽  
Natural Organic Compounds ◽  
Mass Spectrogram ◽  
Urease Enzyme ◽  
Dual Inhibitors ◽  
Inhibition Studies ◽  
First Time

Abstract Twenty seven (1–27) known natural organic compounds were isolated for first time from two species of Iris, i.e. loczyi and Iris unguicularis. The structures of these compounds were deduced from the spectral data of NMR, IR, and mass spectrogram. These were evaluated against urease and carbonic anhydrase inhibition studies. For carbonic anhydrase-II inhibition studies, these compounds were evaluated by biochemical mechanism based in vitro bio-assay. Some compounds showed significant inhibition against CA-II enzyme. Compartively, compound (12) showed IC50 value of 17.60 ± 0.08 μM against urease enzyme, while compound (3) was found to be most active against carbonic anhydrase-II, having an IC50 value of 66.27 ± 0.89 μM. Izalpinin (3), 5,7-dihydroxy-2′,6-dimethoxyisoflavone (9), 4′,5,7-trihydroxy-6-methoxyflavanone (16), 4′,5,7-trihydroxy-3′,8-dimethoxyflavanone (20), 8-methoxyeriodictyol (21), and mangiferin (26) were found to be dual inhibitors of both the enyzmes. The most active compounds were docked using Autodock Vina and i-GEMDOCK softwares. The docking and in-vitro results are in agreement which showed secondary interactions with the enzymes. The compounds can serve as therapeutic agents to treat urease and carbonic anhydrase associated disorders.

scholarly journals Structure Revision and Protein Tyrosine Phosphatase Inhibitory Activity of Drazepinone

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 714
Author(s):  
Fei Cao ◽  
Li Pan ◽  
Wen-Bin Gao ◽  
Yun-Feng Liu ◽  
Cai-Juan Zheng ◽  
...  
Keyword(s):  
Detailed Analysis ◽  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Chemical Shifts ◽  
Tyrosine Phosphatase ◽  
2D Nmr ◽  
Nmr Data ◽  
Structure Revision ◽  
Ic50 Values

From the marine-derived fungus Penicillium sumatrense (Trichocomaceae), a pair of enantiomers [(+)-1 and (−)-1] were isolated with identical 1D NMR data to drazepinone, which was originally reported to have a trisubstituted naphthofuroazepinone skeleton. In this study, we confirmed the structures of the two enantiomers as drazepinone and revised their structures by detailed analysis of extensive 2D NMR data and a comparison of the calculated 13C chemical shifts, ECD, VCD, and ORD spectra with those of the experiment ones. (+)-1 and (−)-1 were evaluated for their PTP inhibitory activity in vitro. (−)-1 showed selective PTP inhibitory activity against PTP1B and TCPTP with IC50 values of 1.56 and 12.5 μg/mL, respectively.

scholarly journals PTP1B INHIBITORS FROM ISODON TERNIFOLIUS COLLECTED IN VIETNAM

2020 ◽  
Vol 58 (5) ◽  
pp. 533
Author(s):  
Nguyen Phi-Hung
Keyword(s):  
Enzyme Activity ◽  
Inhibitory Activity ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Chemical Structures ◽  
Whole Plant ◽  
Ic50 Values ◽  
Ptp1b Inhibitors ◽  
First Time

From the whole plant of Isodon ternifolius collected in Vietnam, four triterpens including ursaldehyde (1), ursolic acid (2), b-sitosterol (3) and b-sitosteryl ferulate (4) were purified. Their chemical structures were determined by interpretation of NMR and MS data and comparison with the literatures. Compounds 1-4 were evaluated for their inhibitory activity against PTP1B enzyme activity using in vitro assay. Compounds 1 and 2 displayed potential activities with IC50 values of 16.92 ± 0.12 and 3.42 ± 0.45 μM, respectively. This is the first time that compounds 1 and 4 have been isolated from the Isodon genus and I. ternifolius has been evaluated for the PTP1B inhibitory activity.

The inhibitory Effects of Some Artificial Food Colorings on α-amylase and α-glucosidase: In Vitro and In Silico Studies

2021 ◽  
Vol 17 ◽  
Author(s):  
Reguia Mahfoudi ◽  
Amar Djeridane ◽  
Djilali Tahri ◽  
Mohamed Yousfi
Keyword(s):  
In Silico ◽  
Hydrophobic Interactions ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Qsar Study ◽  
Molegro Virtual Docker ◽  
Artificial Food ◽  
In Silico Studies ◽  
Ic50 Values

Background: Inhibition of α-amylase and α-glucosidase is considered as an important therapeutic target to manage type 2 diabetes mellitus (T2DM), reducing postprandial hyperglycemia (PPHG). Objective: The present work explored the antidiabetic activities of five artificial food colorings by α-amylase and α-glucosidase enzyme inhibition in vitro and in Silico. Methods: In this study, inhibition of α-amylase and α-glucosidase were evaluated. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (food colorings) was followed by QSAR and molecular docking studies. Results: The in vitro results obtained show that the blue patent (SIN131) exhibited more potent inhibition with IC50 values of 0.03± 0.01 mM and 0.014±0.001 mM against α-amylase and α-glucosidase inhibition respectively compared to acarbose. The QSAR study found a strong correlation between IC50 values with four molecular descriptors. This linear regression confirms that a strong polarity (Apol) and a low hydrophobia (ALogP) favor the inhibitory effect of these colorings toward both enzymes. Also, a negative role of the number of heavy atoms has been demonstrated in the phenomenon of inhibition of this enzyme. Finally, the descriptor εlumo (electronic affinity) plays a crucial role on the inhibitory power of these dyes toward both enzymes by electron transfer. The virtual screening of the inhibition of α-amylase and α-glucosidase by these colorings, using Molegro Virtual Docker (MVD), allowed us to obtain stable complexes with interaction energies resulting from the place of hydrogen bonds and several hydrophobic interactions. However, the sulfonate groups of these colorings can be the major factors in the inhibition of these enzymes. On the other hand, Rerank Score with the pose are perfectly correlated (R2> 0.76) to the inhibitory activity of these food colorings measured experimentally. Conclusion: The present study suggests that the Blue Patent V (SIN131) effectively act as α-amylase and α-glucosidase inhibitor leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels.

Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

MedPharmRes ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 15-25
Author(s):  
Dao Tran ◽  
Son Tran ◽  
Vi Nguyen ◽  
Tri Le ◽  
Minh Thai ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Condensation Reaction ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Studies ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Ellman’S Method

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

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