Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking

2017 ◽  
Vol 14 (8) ◽  
pp. e1700035 ◽  
Author(s):  
Aamer Saeed ◽  
Parvez Ali Mahesar ◽  
Pervaiz Ali Channar ◽  
Fayaz Ali Larik ◽  
Qamar Abbas ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Mechanism ◽  
Urease Inhibitors ◽  
Design And Synthesis

scholarly journals Exploring Amantadine Derivatives as Urease Inhibitors: Molecular Docking and Structure–Activity Relationship (SAR) Studies

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7150
Author(s):  
Atteeque Ahmed ◽  
Aamer Saeed ◽  
Omar M. Ali ◽  
Zeinhom M. El-Bahy ◽  
Pervaiz Ali Channar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Amino Acid Residue ◽  
Alkyl Chain ◽  
Kinetic Mechanism ◽  
Vital Role ◽  
Urease Inhibitors ◽  
Design And Synthesis ◽  
Ic50 Value

This article describes the design and synthesis of a series of novel amantadine-thiourea conjugates (3a–j) as Jack bean urease inhibitors. The synthesized hybrids were assayed for their in vitro urease inhibition. Accordingly, N-(adamantan-1-ylcarbamothioyl)octanamide (3j) possessing a 7-carbon alkyl chain showed excellent activity with IC50 value 0.0085 ± 0.0011 µM indicating that the long alkyl chain plays a vital role in enzyme inhibition. Whilst N-(adamantan-1-ylcarbamothioyl)-2-chlorobenzamide (3g) possessing a 2-chlorophenyl substitution was the next most efficient compound belonging to the aryl series with IC50 value of 0.0087 ± 0.001 µM. The kinetic mechanism analyzed by Lineweaver–Burk plots revealed the non-competitive mode of inhibition for compound 3j. Moreover, in silico molecular docking against target protein (PDBID 4H9M) indicated that most of the synthesized compounds exhibit good binding affinity with protein. The compound 3j forms two hydrogen bonds with amino acid residue VAL391 having a binding distance of 1.858 Å and 2.240 Å. The interaction of 3j with amino acid residue located outside the catalytic site showed its non-competitive mode of inhibition. Based upon these results, it is anticipated that compound 3j may serve as a lead structure for the design of more potent urease inhibitors.

scholarly journals Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

Heliyon ◽  
2020 ◽  
Vol 6 (10) ◽  
pp. e05290
Author(s):  
Vagish Channa Basappa ◽  
Vivek Hamse Kameshwar ◽  
Karthik Kumara ◽  
Dileep Kumar Achutha ◽  
Lokanath Neratur Krishnappagowda ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Design And Synthesis ◽  
In Silico Molecular Docking

Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation

2020 ◽  
Vol 102 ◽  
pp. 104090
Author(s):  
Adel A. Marzouk ◽  
Salah A. Abdel-Aziz ◽  
Kamal S. Abdelrahman ◽  
Amira S. Wanas ◽  
Ahmed M. Gouda ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Design And Synthesis

scholarly journals Design and Synthesis of Various 5′-Deoxy-5′-(4-Substituted-1,2,3-Triazol-1-yl)-Uridine Analogues as Inhibitors of Mycobacterium tuberculosis Mur Ligases

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4953
Author(s):  
Vincent Hervin ◽  
Ritu Arora ◽  
Jyoti Rani ◽  
Srinivasan Ramchandran ◽  
Urmi Bajpai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Active Site ◽  
Inhibitory Effect ◽  
Natural Substrate ◽  
Screening Assay ◽  
One Pot ◽  
Peptidoglycan Biosynthesis ◽  
Design And Synthesis ◽  
Structure Activity

The synthesis of hitherto unknown 5′-deoxy-5′-(4-substituted-1,2,3-triazol-1-yl)-uridine and its evaluation, through an one-pot screening assay, against MurA-F enzymes involved in Mycobacterium tuberculosis (Mtb), are described. Starting from UDP-N-acetylmuramic acid (UDP-MurNAc), the natural substrate involved in the peptidoglycan biosynthesis, our strategy was to substitute the diphosphate group of UDP-MurNAc by a 1,2,3-triazolo spacer under copper-catalyzed azide-alkyne cycloaddition conditions. The structure-activity relationship was discussed and among the 23 novel compounds developed, N-acetylglucosamine analogues 11c and 11e emerged as the best inhibitors against the Mtb MurA-F enzymes reconstruction pathway with an inhibitory effect of 56% and 50%, respectively, at 100 μM. Both compounds are selective inhibitors of Mtb MurE, the molecular docking and molecular dynamic simulation suggesting that 11c and 11e are occupying the active site of Mtb MurE ligase.

scholarly journals Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4238
Author(s):  
Sergiy M. Kovalenko ◽  
Oleksandr G. Drushlyak ◽  
Svitlana V. Shishkina ◽  
Irina S. Konovalova ◽  
Illia O. Mariutsa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Combinatorial Libraries ◽  
Docking Studies ◽  
X Ray Diffraction ◽  
Docking Simulations ◽  
Design And Synthesis ◽  
Hbv Replication ◽  
Biological Studies ◽  
Reliable Design

Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CH3I has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CH3I led to the formation of both O- and N-methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of O-methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, 1H-NMR, 13C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate’s anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.

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