5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Background: Infectious diseases symbolize a global consequential strain on public health security and impact on the socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in crucial need for the discovery and development of novel entity for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using classical methods of organic synthesis. Results: All 20 synthesized compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species. It should be mentioned that all compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Furthermore, 18 compounds appeared to be more potent than streptomycin against Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli. Three the most active compounds 4h, 5b, and 5g appeared to be more potent against MRSA than ampicillin, while streptomycin did not show any bactericidal activity. All three compounds displayed better activity also against resistant strains P. aeruginosa and E. coli than ampicillin. Furthermore, all compounds were able to inhibit biofilm formation 2- to 4-times more than both reference drugs. Compounds were evaluated also for their antifungal activity against eight species. The evaluation revealed that all compounds exhibited antifungal activity better than the reference drugs bifonazole and ketoconazole. Molecular docking studies on antibacterial and antifungal targets were performed in order to elucidate the mechanism of antibacterial activity of synthesized compounds. Conclusion: All tested compounds showed good antibacterial and antifungal activity better than that of reference drugs and three the most active compounds could consider as lead compounds for the development of new more potent agents.

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Griseofulvin Derivatives: Synthesis, Molecular Docking and Biological Evaluation

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190523080136 ◽

2019 ◽

Vol 19 (13) ◽

pp. 1145-1161 ◽

Cited By ~ 4

Author(s):

Victor Kartsev ◽

Athina Geronikaki ◽

Anthi Petrou ◽

Boris Lichitsky ◽

Marina Kostic ◽

...

Keyword(s):

Antimicrobial Activity ◽

Molecular Docking ◽

Antifungal Activity ◽

Organic Synthesis ◽

Docking Studies ◽

Biological Evaluation ◽

Design And Synthesis ◽

Microdilution Method ◽

New Compounds ◽

Better Than

Background:Griseofulvin - a mold metabolite produced by Penisilium griseofulvum is known as an antifungal drug.Objective:Thus, the goal of this paper is the design and synthesis of new griseofulvin derivatives and evaluation of their antifungal activity.Methods:Forty-two new compounds were synthesized using classical methods of organic synthesis and evaluated for their antimicrobial activity by microdilution method.Results:All forty-two new compounds exhibited very good activity against eight tested micromycetes with MIC ranging from 0.0075-0.055 mg/ml and MFC from 0.02-024 mg/ml. All compounds exhibited better activity than reference drugs ketoconazole (7-42 times) and bifonazole (3-16 fold). The most promising was compound 15. The most sensitive fungal was found to be T. viride, while the most resistant, as was expected, was A. fumigatus. It should be mentioned that most of compounds exhibited better activity than griseofulvin.:The molecular docking studies revealed that the most active compound have the same hydrophobic and H-bonding interactions with Thr276 residue observed for griseofulvin forming 3 hydrogen bonds while griseofulvin only one. In general, the molecular docking results coincide with experimental.Conclusion:Forty-two giseofulvin derivatives were designed, synthesized and evaluated for antimicrobial activity. These derivatives revealed good antifungal activity, better than reference drugs ketoconazole, bifonazole, and griseofulvin as well.

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Antibacterial activity of xylose-derived LpxC inhibitors – synthesis, biological evaluation and molecular docking studies

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104603 ◽

2020 ◽

pp. 104603

Author(s):

Alexander Dreger ◽

Katharina Hoff ◽

Oriana Agoglitta ◽

Sven-Kevin Hotop ◽

Mark Brönstrup ◽

...

Keyword(s):

Antibacterial Activity ◽

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies

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Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

Molecules ◽

10.3390/molecules24152815 ◽

2019 ◽

Vol 24 (15) ◽

pp. 2815 ◽

Cited By ~ 10

Author(s):

Pisano ◽

Kumar ◽

Medda ◽

Gatto ◽

Pal ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Molecular Docking ◽

Structural Features ◽

Docking Studies ◽

Trna Synthetase ◽

Hydroxyl Groups ◽

Bacterial Strains ◽

Active Compounds ◽

Molecular Docking Studies

Antibiotic resistance is one of the main public health concerns of this century. This resistance is also associated with oxidative stress, which could contribute to the selection of resistant bacterial strains. Bearing this in mind, and considering that flavonoid compounds are well known for displaying both activities, we investigated a series of hydroxy-3-arylcoumarins with structural features of flavonoids for their antibacterial activity against different bacterial strains. Active compounds showed selectivity against the studied Gram-positive bacteria compared to Gram-negative bacteria. 5,7-Dihydroxy-3-phenylcoumarin (compound 8) displayed the best antibacterial activity against Staphylococcus aureus and Bacillus cereus with minimum inhibitory concentrations (MICs) of 11 g/mL, followed by Staphylococcus aureus (MRSA strain) and Listeria monocytogenes with MICs of 22 and 44 g/mL, respectively. Moreover, molecular docking studies performed on the most active compounds against Staphylococcus aureus tyrosyl-tRNA synthetase and topoisomerase II DNA gyrase revealed the potential binding mode of the ligands to the site of the appropriate targets. Preliminary structure–activity relationship studies showed that the antibacterial activity can be modulated by the presence of the 3-phenyl ring and by the position of the hydroxyl groups at the coumarin scaffold.

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Appendix A. dithioloquinolinethiones as new potential multitargeted antibacterial and antifungal agents: Synthesis, biological evaluation and molecular docking studies

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2019.04.046 ◽

2019 ◽

Vol 175 ◽

pp. 201-214 ◽

Cited By ~ 3

Author(s):

V. Kartsev ◽

Khidmet S. Shikhaliev ◽

A. Geronikaki ◽

Svetlana M. Medvedeva ◽

Irina V. Ledenyova ◽

...

Keyword(s):

Molecular Docking ◽

Antifungal Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies ◽

Antibacterial And Antifungal

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5-Benzyliden-2-(5-Methylthiazol-2-Ylimino)Thiazolidin-4-Ones as Antimicrobial Agents. Design, Synthesis, Biological Evaluation and Molecular Docking Studies

Antibiotics ◽

10.3390/antibiotics10030309 ◽

2021 ◽

Vol 10 (3) ◽

pp. 309

Author(s):

Michelyne Haroun ◽

Christophe Tratrat ◽

Aggeliki Kolokotroni ◽

Anthi Petrou ◽

Athina Geronikaki ◽

...

Keyword(s):

Molecular Docking ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Design Synthesis ◽

Molecular Docking Studies ◽

E Coli ◽

Antibacterial And Antifungal Activities ◽

Lanosterol Demethylase

In this study, we report the design, synthesis, computational and experimental evaluation of the antimicrobial activity, as well as docking studies of new 5-methylthiazole based thiazolidinones. All compounds demonstrated antibacterial efficacy, some of which (1,4,10 and 13) exhibited good activity against E. coli and B. cereus. The evaluation of antibacterial activity against three resistant strains, MRSA, P. aeruginosa and E. coli, revealed that compound 12 showed the best activity, higher than reference drugs ampicillin and streptomycin, which were inactive or exhibited only bacteriostatic activity against MRSA, respectively. Ten out of fifteen compounds demonstrated higher potency than reference drugs against a resistant strain of E. coli, which appeared to be the most sensitive species to our compounds. Compounds 8, 13 and 14 applied in a concentration equal to MIC reduced P. aeruginosa biofilm formation by more than 50%. All compounds displayed antifungal activity, with compound 10 being the most active. The majority of compounds showed better activity than ketoconazole against almost all fungal strains. In order to elucidate the mechanism of antibacterial and antifungal activities, molecular docking studies on E. coli Mur B and C. albicans CYP51 and dihydrofolate reductase were performed. Docking analysis of E. coli MurB indicated a probable involvement of MurB inhibition in the antibacterial mechanism of tested compounds while docking to 14α-lanosterol demethylase (CYP51) and tetrahydrofolate reductase of Candida albicans suggested that probable involvement of inhibition of CYP51 reductase in the antifungal activity of the compounds. Potential toxicity toward human cells is also reported.

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