Identification of novel pyrazole–rhodanine hybrid scaffolds as potent inhibitors of aldose reductase: design, synthesis, biological evaluation and molecular docking analysis

A series of novel pyrazole–rhodanine derivatives was designed, synthesized, and biologically evaluated for their potential inhibitory effect on both aldehyde reductase (ALR1) and aldose reductase (ALR2).

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Novel Derivatives of Rhodanine-3-Hippuric Acid as Active Inhibitors of Aldose Reductase: Synthesis, Biological Evaluation, and Molecular Docking Analysis

Russian Journal of Bioorganic Chemistry ◽

10.1134/s1068162019050066 ◽

2019 ◽

Vol 45 (5) ◽

pp. 405-415

Author(s):

Stephen Kumar Celestina ◽

Kaveri Sundaram ◽

Subban Ravi

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Hippuric Acid ◽

Biological Evaluation ◽

Docking Analysis ◽

Derivatives Of ◽

Molecular Docking Analysis

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Tetrahydroquinolinone derivatives as potent P-glycoprotein inhibitors: design, synthesis, biological evaluation and molecular docking analysis

MedChemComm ◽

10.1039/c7md00178a ◽

2017 ◽

Vol 8 (10) ◽

pp. 1919-1933 ◽

Cited By ~ 10

Author(s):

S. Ranjbar ◽

O. Firuzi ◽

N. Edraki ◽

O. Shahraki ◽

L. Saso ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Phenyl Ring ◽

Biological Evaluation ◽

Design Synthesis ◽

Docking Analysis ◽

P Glycoprotein ◽

Glycoprotein Inhibitors ◽

Molecular Docking Analysis

Tetrahydroquinolinones bearing a phenyl ring with electron-withdrawing substitution showed remarkable P-glycoprotein inhibitory activity and significantly increased rhodamine accumulation in MES-SA/DX5 cells.

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Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

10.21203/rs.3.rs-54676/v1 ◽

2020 ◽

Author(s):

Mohsinul Mulk Bacha ◽

Humaira Nadeem ◽

Shafiq Ur Rehman ◽

Sadia Sarwar ◽

Aqeel Imran ◽

...

Keyword(s):

Acetic Acid ◽

Molecular Docking ◽

Aldose Reductase ◽

Diabetic Complications ◽

Docking Studies ◽

Biological Evaluation ◽

Aldehyde Reductase ◽

Standard Drug ◽

Molecular Docking Studies

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.

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Quorum Sensing Inhibiting Activity of Cefoperazone and Its Metallic Derivatives on Pseudomonas aeruginosa

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.716789 ◽

2021 ◽

Vol 11 ◽

Author(s):

Nourhan G. Naga ◽

Dalia E. El-Badan ◽

Heba S. Rateb ◽

Khaled M. Ghanem ◽

Mona I. Shaaban

Keyword(s):

Pseudomonas Aeruginosa ◽

Molecular Docking ◽

Quorum Sensing ◽

Virulence Factors ◽

Cobalt Complex ◽

Inhibitory Effect ◽

Iron Complex ◽

Dilution Method ◽

Docking Analysis ◽

Molecular Docking Analysis

The last decade has witnessed a massive increase in the rate of mortalities caused by multidrug-resistant Pseudomonas aeruginosa. Therefore, developing new strategies to control virulence factors and pathogenicity has received much attention. One of these strategies is quorum sensing inhibition (QSI) which was developed to control Pseudomonas infection. This study aims to validate the effect of one of the most used β-lactam antibiotics; cefoperazone (CFP) and its metallic-derivatives on quorum sensing (QS) and virulence factors of P. aeruginosa. Assessment of quorum sensing inhibitory activity of CFP, cefoperazone Iron complex (CFPF) and cefoperazone Cobalt complex (CFPC) was performed by using reporter strain Chromobacterium violaceum ATCC 12472. Minimal inhibitory concentration (MIC) was carried out by the microbroth dilution method. The influence of sub-MICs (1/4 and 1/2 MICs) of CFP, CFPF and CFPC on virulence factors of P. aeruginosa was evaluated. Data was confirmed on the molecular level by RT-PCR. Also, molecular docking analysis was conducted to figure out the possible mechanisms of QSI. CFP, CFPF, and CFPC inhibited violacein pigment production of C. violaceum ATCC 12472. Sub-MICs of CFP (128- 256 μg/mL), and significantly low concentrations of CFPC (0.5- 16 μg/mL) and CFPF (0.5- 64 μg/mL) reduced the production of QS related virulence factors such as pyocyanin, protease, hemolysin and eliminated biofilm assembly by P. aeruginosa standard strains PAO1 and PA14, and P. aeruginosa clinical isolates Ps1, Ps2, and Ps3, without affecting bacterial viability. In addition, CFP, CFPF, and CFPC significantly reduced the expression of lasI and rhlI genes. The molecular docking analysis elucidated that the QS inhibitory effect was possibly caused by the interaction with QS receptors. Both CFPF and CFPC interacted strongly with LasI, LasR and PqsR receptors with a much high ICM scores compared to CFP that could be the cause of elimination of natural ligand binding. Therefore, CFPC and CFPF are potent inhibitors of quorum sensing signaling and virulence factors of P. aeruginosa.

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