New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.
Anti-Bacterial Agents
/ chemical synthesis
Antifungal Agents
/ chemical synthesis
Caffeic Acids
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Design
Fungi
/ drug effects
Gram-Negative Bacteria
/ drug effects
Gram-Positive Bacteria
/ drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Antimicrobial activity
CYP51
Caffeic acid derivatives
Docking
Gyrase
PASS
Phenolic acids.
Journal
Current topics in medicinal chemistry
ISSN: 1873-4294
Titre abrégé: Curr Top Med Chem
Pays: United Arab Emirates
ID NLM: 101119673
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
11
2018
revised:
31
12
2018
accepted:
07
01
2019
pubmed:
25
1
2019
medline:
25
4
2019
entrez:
25
1
2019
Statut:
ppublish
Résumé
Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.
Sections du résumé
BACKGROUND
BACKGROUND
Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity.
OBJECTIVE
OBJECTIVE
The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi.
METHODS
METHODS
In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method.
RESULTS
RESULTS
Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg).
CONCLUSION
CONCLUSIONS
Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.
Identifiants
pubmed: 30674263
pii: CTMC-EPUB-96013
doi: 10.2174/1568026619666190122152957
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antifungal Agents
0
Caffeic Acids
0
caffeic acid
U2S3A33KVM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
292-304Informations de copyright
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