scholarly journals Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

2022 ◽  
Vol 8 ◽  
Author(s):  
Entesar A. Hassan ◽  
Ihsan A. Shehadi ◽  
Awatef M. Elmaghraby ◽  
Hadir M. Mostafa ◽  
Salem E. Zayed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Docking Analysis ◽  
Excellent Activity ◽  
New Compounds

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

scholarly journals Synthesis, biological evaluation and molecular docking studies of new 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonate derivatives on human aldose reductase enzyme

2021 ◽  
Author(s):  
Gül Özdemir ◽  
Namık Kılınç ◽  
Sevda Manap ◽  
Murat Beytur ◽  
Muzaffer Alkan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Diffusion Method ◽  
Alkyl Aryl ◽  
Molecular Docking Studies ◽  
New Compounds

A series of 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (3) were synthesized from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 2-ethoxy-4-formyl-phenyl benzenesulfonate (2). N-acetyl derivatives (4) of compounds 3 were also obtained. Then, the compounds 3 have been treated with morpholine and 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize 2-ethoxy-4-{[1-(morpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (5) and 2-ethoxy-4-{[1-(2,6-dimethylmorpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (6), respectively. The structures of twenty-six new compounds were identified by using elemental analysis, IR, 1H NMR, 13C NMR, and MS spectral data. In addition, in vitro antibacterial activities of the new compounds were evaluated against six bacteria such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klepsiella pneumonia according to agar well diffusion method. Furthermore, in order to determine the possible antidiabetic properties of the synthesized 1,2,4-triazole derivatives, inhibition effects on the AR enzyme were investigated and molecular docking studies were carried out to determine the receptor-ligand interactions of these compounds. IC50 values of triazole-derived compounds (6a, 6b, 6d-g) against AR enzyme were determined as 0.95 µM, 0.75 µM, 1.83 µM, 0.62 µM, 1.05 µM, 1.06 µM, respectively. Considering the docking scores and binding energies obtained docking studies, it has been shown that molecules fit very well to the active site of the AR enzyme.

Synthesis, in silico pharmacokinetics and biological evaluation of some new thiazolidinedione as PPAR-γ agonists and antibacterial agents

2021 ◽  
Vol 18 ◽  
Author(s):  
Zohor Mohammad Mahdi Alzhrani ◽  
Mohammad Mahboob Alam ◽  
Syed Nazreen
Keyword(s):  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Biological Evaluation ◽  
New Drugs ◽  
Diabetic Patients ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Ppar Γ

Background: The frequent uses of antimicrobial agents to treat infections in diabetic patients make them more drug resistance than non diabetic patients which accounts for higher mortality rate of diabetic patients. Therefore, it is a necessity today to synthesize new drugs with dual mode of action as antidiabetic and antibacterial agents. In the present work, new derivatives containing thiazolidinedione and 1,3,4-oxadiaozle have been synthesized and screened for PPAR-γ and antibacterial activities. Methods: Compound 5-12 have been synthesized from 2-methoxy benzaldehyde and thiazolidinedione and characterized using different spectroscopic techniques such as IR, NMR and mass spectrometry. These compounds were tested for in vitro PPAR-γ transactivation, PPAR-γ gene expression and antibacterial activities. Finally molecular docking was carried out to see the binding interactions of molecules with the target protein. Results: All the compounds follow Lipinski rule suggesting the synthesized derivatives have good drug likeness properties. Compound 11 and 12 exhibited promising PPAR-γ transactivation with 73.69% and 76.50%, respectively as well as showed significant antibacterial activity with comparable MIC of 3.12 μg/disc to standard drug amoxicillin. The docking result was found to be in consistent with the in vitro PPAR-γ transactivation results. Conclusion: Compounds 11 and 12 can be further investigated as lead molecules for the development of new and effective antidiabetic and antibacterial agents.

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.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

scholarly journals Enantioselective Synthesis, Tautomerism, Molecular Docking And Biological Evaluation of 4-Hydroxy-3-(3-Oxo-1-Phenylbutyl)-2H-Chromen-2-One Analogues

2021 ◽  
Author(s):  
Zakia Afzal ◽  
Naghmana Rashid ◽  
Humaira Nadeem ◽  
Arif-ullah Khan
Keyword(s):  
Molecular Docking ◽  
Anticoagulant Activity ◽  
Enantiomeric Excess ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Chiral Hplc ◽  
Aryl Group ◽  
Standard Drug ◽  
Antibacterial And Antifungal Activities

Abstract Keeping in view the aim of better alternatives of 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one (warfarin), eleven analogs of warfarin have been synthesized with the goal to increase enantioselectivity of (S) enantiomer by using appropriate catalyst and minimize tautomerism by replacing methyl group of the side chain with aryl group. There are many reports of the serious complications with warfarin use, which are associated with the tautomeric forms of warfarin. The key step was highly enantioselective Michael addition of variously substituted chalcone and 4-hydroxycoumarin by using cinchona based 9-amino-9-deoxyepiquinine as chiral catalyst. Synthesized compounds were characterized by IR, 1HNMR,13CNMR, EIMS and CD studies. Enantiomeric excess (%ee) was determined by chiral HPLC which was upto 98%. Synthesized analogues were screened for anticoagulant, antibacterial and antifungal activities. In-vitro anticoagulant activity was evaluated by plasma recalcification time (PRT) method and out of eleven, ten synthesized compounds showed improved IC50 values as compaired to IC50 values of standard drug warfarin. Compound 4 showed 68.25% inhibation against staphylococcus aureus and compound 7 showed 68% inhibation against bacillus subtillis, gram positive strains of bacteria, compound 6 shows 70% inhibation against fungal strain candida albicans. Furthermore, molecular docking studies were carried out with Vitamin K1 epoxide reductase VKOR1 receptor 3kp9, a potential target of warfarin for anticoagulant activity.

scholarly journals 1,2,3-triazole-dithiocarbamate-naphthalimides: Synthesis, characterization, and biological evaluation

2020 ◽  
pp. 174751982096697
Author(s):  
Qiu Mei Chen ◽  
Zhen Li ◽  
Guang Xun Tian ◽  
Yi Chen ◽  
Xiang Hua Wu
Keyword(s):  
Antimicrobial Agents ◽  
Analytical Techniques ◽  
Antibacterial Activities ◽  
Biological Evaluation ◽  
Antitumor Activities ◽  
X Ray Crystallography ◽  
Mtt Method ◽  
New Compounds ◽  
Clinical Drug

Fifteen novel dithiocarbamate-derived naphthalimides as a type of potential anticancer and antimicrobial agents were synthesized and characterized by spectral and analytical techniques. The structures of 2b, 5a, and 7b were established by X-ray crystallography. Their in vitro antitumor activities were evaluated by the MTT method against MDA-MB-231, HepG-2, PC12, as well as A549. Based on the results of the MTT assay, compound 7c bearing a morpholinyl substituent displayed the highest activity and selectivity toward HepG-2 cancer cells with an IC50 of 10.86 µM. All new compounds were screened for their antimicrobial activity against Candida albicans, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. The preliminary results showed that compound 7d (an N-methyl piperazine) showed high efficacy against B. subtilis with a minimum inhibitory concentration value of 7.6 µM, which was superior to that of the clinical drug, Cefuroxim. It is found that the anticancer and antibacterial activities of the dithiocarbamate-naphthalimide derivatives were significantly enhanced when bearing a 1,2,3-triazole group.

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 ◽  
Sumera Zaib ◽  
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. The binding site analysis of potent compounds revealed similar interactions as were found by cognate ligands within the active sites of enzymes.

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.

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