Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site

2011 ◽  
Vol 19 (4) ◽  
pp. 1381-1389 ◽  
Author(s):  
Serdar Durdagi ◽  
Murat Şentürk ◽  
Deniz Ekinci ◽  
Halis Türker Balaydın ◽  
Süleyman Göksu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Mode ◽  
Docking Studies ◽  
Enzyme Active Site

scholarly journals 2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site

2020 ◽  
Vol 56 (59) ◽  
pp. 8297-8300
Author(s):  
Murat Bozdag ◽  
Claudiu T. Supuran ◽  
Davide Esposito ◽  
Andrea Angeli ◽  
Fabrizio Carta ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Mode ◽  
Lead Compound ◽  
Carbonic Anhydrase Inhibitors ◽  
Enzyme Active Site

2-Mercaptobenzoxazole represents an interesting lead compound alternative to the classical sulfonamides for the development of selective carbonic anhydrase inhibitors.

scholarly journals Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2418
Author(s):  
Zuo-Peng Zhang ◽  
Ze-Fa Yin ◽  
Jia-Yue Li ◽  
Zhi-Peng Wang ◽  
Qian-Jie Wu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Docking Studies ◽  
Active Site Residues ◽  
Single Crystal Diffraction ◽  
Docking Analysis ◽  
X Ray ◽  
Active Site Cavity ◽  
Molecular Docking Analysis ◽  
Positive Controls

To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the active site cavity of hCA IX by forming sufficient interactions with active site residues. The fragment of thiazolidinone played an important role in the binding of the molecules to the active site.

scholarly journals Aryl-4,5-dihydro-1H-pyrazole-1-carboxamide Derivatives Bearing a Sulfonamide Moiety Show Single-digit Nanomolar-to-Subnanomolar Inhibition Constants against the Tumor-associated Human Carbonic Anhydrases IX and XII

2020 ◽  
Vol 21 (7) ◽  
pp. 2621
Author(s):  
Priya Hargunani ◽  
Nikhil Tadge ◽  
Mariangela Ceruso ◽  
Janis Leitans ◽  
Andris Kazaks ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
Phenyl Ring ◽  
Drug Targets ◽  
Binding Mode ◽  
Docking Studies ◽  
Carbonic Anhydrases ◽  
Single Digit ◽  
Ca Ix ◽  
Shed Light

A series of new 3-phenyl-5-aryl-N-(4-sulfamoylphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide derivatives was designed here, synthesized, and studied for carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity against the human (h) isozymes I, II, and VII (cytosolic, off-target isoforms), and IX and XII (anticancer drug targets). Generally, CA I was not effectively inhibited, whereas effective inhibitors were identified against both CAs II (KIs in the range of 5.2–233 nM) and VII (KIs in the range of 2.3–350 nM). Nonetheless, CAs IX and XII were the most susceptible isoforms to this class of inhibitors. In particular, compounds bearing an unsubstituted phenyl ring at the pyrazoline 3 position showed 1.3–1.5 nM KIs against CA IX. In contrast, a subset of derivatives having a 4-halo-phenyl at the same position of the aromatic scaffold even reached subnanomolar KIs against CA XII (0.62–0.99 nM). Docking studies with CA IX and XII were used to shed light on the derivative binding mode driving the preferential inhibition of the tumor-associated CAs. The identified potent and selective CA IX/XII inhibitors are of interest as leads for the development of new anticancer strategies.

ChemInform Abstract: An Inhibitor-Like Binding Mode of a Carbonic Anhydrase Activator within the Active Site of Isoform II.

ChemInform ◽  
2012 ◽  
Vol 43 (10) ◽  
pp. no-no
Author(s):  
Khyati Dave ◽  
Marc A. Ilies ◽  
Andrea Scozzafava ◽  
Claudia Temperini ◽  
Daniela Vullo ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Mode

Enzyme Inhibition, Kinetic, and Molecular Docking Studies of α-glucosidase

2020 ◽  
Vol 16 (2) ◽  
pp. 155-161
Author(s):  
Ebrahim S. Moghadam ◽  
Mohammad A. Faramarzi ◽  
Somayeh Imanparast ◽  
Mohsen Amini
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Kinetic Studies ◽  
Developed Countries ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Active Site Residues ◽  
Efficient Treatment ◽  
Enzyme Active Site

Background: Diabetes mellitus (DM) is an important global health problem especially in developed countries and insufficient lifestyle induces this phenomenon. Finding efficient treatment for DM is an interesting goal for researchers. Objective: Herein we tried to design and synthesize a series of quinazoline derivatives and investigate their bioactivity as possible α-Glucosidase inhibitor agents. Method: Compounds 1-14 were synthesized using a multicomponent reaction. 1HNMR, 13C NMR, MS, and IR spectroscopy were used for the characterization of synthesized compounds. α- Glucosidase inhibitory activity of compounds 1-14 was evaluated using p-nitrophenyl‐α‐Dglucopyranoside (pNPG) as a substrate of the α-glucosidase enzyme (EC3.2.1.20, Saccharomyces cerevisiae). The mechanism of inhibition of the α-glucosidase enzyme was investigated using kinetic studies. Molecular docking was also done using autodock software to find the possible mode of interaction of compound 8 and the enzyme active site. Results: Most of the tested compounds showed higher activity in inhibition of the enzyme in comparison to the standard, acarbose. Compound 8 exerted the best activity with the IC50 value of 291.5 μM. A kinetic study indicated a competitive inhibition of the α-glucosidase enzyme by compound 8. Finally, docking studies showed the interactions between compound 8 and enzyme active site residues. Conclusion: 2,4-Diarylquinazoline scaffold has good antidiabetic activity, so it is interesting to synthesize more 2,4-diarylquinazoline derivatives and evaluate their antidiabetic activities.

scholarly journals Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and molecular docking studies

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 452-464 ◽  
Author(s):  
Syed Mobasher Ali Abid ◽  
Sana Aslam ◽  
Sumera Zaib ◽  
Syeda Mahwish Bakht ◽  
Matloob Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Potent Inhibitor ◽  
Binding Mode ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Monoamine Oxidases ◽  
Mao B

Binding mode of potent inhibitor (green) & cognate ligand (pink) in the active site of MAO-B.

Synthesis, biological evaluation and docking studies of some novel isatin-3-hydrazonothiazolines

RSC Advances ◽  
2016 ◽  
Vol 6 (65) ◽  
pp. 60826-60844 ◽  
Author(s):  
Maqbool Ahmad ◽  
Humayun Pervez ◽  
Sumera Zaib ◽  
Muhammad Yaqub ◽  
Muhammad Moazzam Naseer ◽  
...  
Keyword(s):  
Active Site ◽  
Binding Mode ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Jack Bean Urease ◽  
Jack Bean

The putative binding mode of compound 6i in the active site of Jack bean urease.

Synthesis, Docking Studies and Biological Evaluation of Novel N-(2-(3-fluorophenyl)- quinolin-5-yl)benzamide Derivatives as Potent Anti-breast Cancer Agents

2020 ◽  
Vol 5 (2) ◽  
pp. 97-102
Author(s):  
Shrimant V. Rathod ◽  
Kailas W. Shinde ◽  
Prashant S. Kharkar ◽  
Chetan P. Shah ◽  
Ajit V. Ingle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Active Site ◽  
Cancer Cell Line ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Assay Method ◽  
Enzyme Active Site ◽  
Kinesin Spindle Protein ◽  
Benzamide Derivatives ◽  
Better Than

A novel series of quinoline benzamide derivatives have been synthesized and screened for their anticancer activity against a breast cancer cell line (MDA-MB-231) by MTT assay method. All the synthesized compounds were confirmed by spectral characterization viz. FTIR, 1H & 13C NMR and MS. All the molecules demonstrated potency less than 35 μM and were better than standard cisplatin but not comparable to doxorubicin. Compound 3i (IC50 = 6.86 μM) exhibited better promising anti-breast cancer activity among various synthesized molecules and in addition, docking of compound 3i into kinesin spindle protein (KSP) active site was performed in order to predict the affinity and the orientation at the enzyme active site.

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