scholarly journals DESIGN, SYNTHESIS, MOLECULAR DOCKING, ADMET STUDIES AND BIOLOGICAL EVALUATION OF PYRAZOLINE INCORPORATED 1, 2, 3-TRIAZOLE BENZENE SULPHONAMIDES

2019 ◽  
pp. 6-15
Author(s):  
SRAVANTHI SILIVERI ◽  
NAGARAJU BASHABOINA ◽  
HARINADHA BABU VAMARAJU ◽  
Shiva Raj
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Anti Inflammatory ◽  
Potassium Oxonate

Objective: The main objective of this work was to design, synthesize and evaluate the novel pyrazoline incorporated 1,2,3-triazole benzene sulphonamides for cytotoxic and anti-gout activities also to perform Insilco molecular docking studies. Methods: Designed compounds were synthesized by condensation of different substituted chalcones (3a-i) with hydrazine hydrate and substituted phenylhydrazines. All the synthesized compounds were characterized on the basis of physical and spectral data. To predict the affinity and activity of the ligand molecule Libdock program was employed to generate different bioactive binding poses of designing molecules at the active site of protein Phosphatidylinositol 3-kinase (PI3Kα). Title compounds were evaluated for cytotoxic activity by using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and anti-gout activity by potassium oxonate induced assay. Results: All the synthesized compounds showed characteristic peaks in FTIR, 1H, 13C NMR and MASS spectral analysis. In molecular docking studies, compound 3i has shown good binding affinity to the active site of PI3Kα with a docking score of 145.031 and 4 hydrogen bonding interactions with least hepatotoxicity and good bioavailability when compared with that of reference ligand KKR exhibited a Libdock score of 88.35. Remaining compounds also have a good binding affinity with a minimum of 2 bonding interactions and having better absorption, distribution, metabolism, elimination and toxicity (ADMET) profile. The same compound (3i) exhibited the highest cytotoxic activity with an IC50 value of 4.54µg/ml. Compound 4d was evaluated for anti-inflammatory activity and it has significantly ameliorated against potassium oxonate induced gout in mice when compared with that of standard drug allopurinol due to its anti-inflammatory property. Conclusion: We designed and synthesized a novel series of title compounds in quantitative yields and performed docking studies. New derivatives have a good binding affinity towards PI3Kα enzyme, good bioavailability, least hepatotoxicity and significant cytotoxic activity.

scholarly journals Microwave-Assisted Synthesis, Molecular Docking Studies and Biological Evaluation of Benzothiazole Containing Novel Indole Derivatives

2021 ◽  
Vol 33 (11) ◽  
pp. 2755-2761
Author(s):  
Shaheen Sultana ◽  
P. Pandian ◽  
B. Rajkamal
Keyword(s):  
Molecular Docking ◽  
Reaction Mechanism ◽  
Anticancer Activity ◽  
Mannich Base ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Microwave Assisted

The synthesis of novel indole derivatives 4a-o using a microwave assisted method via Schiff’s base and Mannich base reaction mechanism was described. Compounds 3a-c were synthesized via reaction of 2-amino benzothiazole with substituted isatin by Schiff base reaction mechanism. Also, indole derivatives 4a-o were synthesized via reaction of compounds 3a-c with substituted benzaldehydes by Mannich base reaction. The biological potentials of the newly synthesized indole derivatives were evaluated for their anthelmintic activity and in vitro anticancer activity by MTT assay. The anticancer activity results suggested that indole derivatives 4c-o have activity against MCF-7 and SKOV3 cells in comparison with doxorubicin as standard drug. Furthermore, the molecular docking studies of these novel derivatives of indole showed good agreement with the biological results when their binding pattern and affinity towards the active site of EGFR was also investigated.

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

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.

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

2015 ◽  
Vol 42 (3) ◽  
pp. 2707-2729 ◽  
Author(s):  
Pravin S. Mahajan ◽  
Mukesh D. Nikam ◽  
Vijay M. Khedkar ◽  
Prakash C. Jha ◽  
Dhiman Sarkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Molecular Docking Studies ◽  
Anti Inflammatory

scholarly journals Molecular Docking Studies, Analgesic and Anti-inflammatory Screening of Some Novel Quinazolin-4-one Derivatives

2021 ◽  
Vol 33 (5) ◽  
pp. 1058-1062
Author(s):  
K.N. Rajini Kanth ◽  
Ch. Jaswanth Kumar ◽  
D. Eswar Tony ◽  
Sk. Munwar ◽  
Rama Rao Nadendla ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Hydrogen Bonding Interactions ◽  
Anti Inflammatory ◽  
Pharmacological Screening ◽  
Analgesic Activities ◽  
Cox 2 Inhibitors ◽  
Further Development

Molecular docking studies was performed on 20 analogous novel quinazolin-4-one derivatives as cox-2 inhibitors using glide tool of maestro 11.4 application of Schrodinger software. Anti-inflammatory and analgesic activities were further evaluated for the compounds. Based on docking studies, the binding affinity of QZN-16 was found to be -10.32 kcal/mol. In order to understand the significance of R-substituents on the quinazoline-4-one nucleus, the findings of hydrogen bonding interactions between designated ligands with binding site region of 4cox were studied. The ligands which are having high docking score were subjected to pharmacological screening. The compound QZN-16 has shown analgesic and anti-inflammatory activity at a dose level of 50 and 100 mg/kg body weight, respectively when compared with standard drug indomethacin. The newly designed quinazoline-4-one derivatives may serve as lead molecules for further development.

scholarly journals In silico molecular docking studies of some phytochemicals against peroxisome-proliferator activated receptor gamma (PPAR-γ)

2018 ◽  
Vol 5 (2) ◽  
pp. 001-005
Author(s):  
H. A. Ahmed ◽  
I. Y. Alkali
Keyword(s):  
Molecular Docking ◽  
Insulin Sensitivity ◽  
Binding Affinity ◽  
Docking Studies ◽  
Peroxisome Proliferator ◽  
Autodock Vina ◽  
Peroxisome Proliferator Activated Receptor ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Ppar Γ

Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in glucose, lipid metabolism, adipocyte proliferation and differentiation and insulin sensitivity. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPAR-γ. TZDs are antidiabetic agents that target adipose tissue and improve insulin sensitivity, and they are currently being used in the treatment of type 2 diabetes. The study was carried out in order to discover new phytochemicals that have the ability to stimulate the PPAR-γ using molecular docking studies. AutoDock vina was used as molecular-docking tool in order to carry out the docking simulations. Nine phytochemicals namely plumbagin, quercetin, isovitexin, mangiferin, syringin, lupe-20-ene-3-one, purine 2, 6-dione, diosmetin and β sitosterol and pioglitazone a standard drug were docked against PPAR-γ using AutoDock vina and the results were analyzed using binding affinity. The results revealed that the compounds have significant binding affinity towards the PPAR-γ comparable to pioglitazone the standard drug. Based on the findings of this study these phytochemicals can serve as source of antidiabetic drugs via the mechanism of inhibition of PPAR-γ.

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