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Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives
- Source :
- Journal of Medicinal Chemistry
- Publication Year :
- 2014
- Publisher :
- American Chemical Society (ACS), 2014.
-
Abstract
- On the basis of recently reported abyssinone II and olympicin A, a series of chemically modified flavonoid phytochemicals were synthesized and evaluated against Mycobacterium tuberculosis and a panel of Gram-positive and -negative bacterial pathogens. Some of the synthesized compounds exhibited good antibacterial activities against Gram-positive pathogens including methicillin resistant Staphylococcus aureus with minimum inhibitory concentration as low as 0.39 μg/mL. SAR analysis revealed that the 2-hydrophobic substituent and the 4-hydrogen bond donor/acceptor of the 4-chromanone scaffold together with the hydroxy groups at 5- and 7-positions enhanced antibacterial activities; the 2',4'-dihydroxylated A ring and the lipophilic substituted B ring of chalcone derivatives were pharmacophoric elements for antibacterial activities. Mode of action studies performed on selected compounds revealed that they dissipated the bacterial membrane potential, resulting in the inhibition of macromolecular biosynthesis; further studies showed that selected compounds inhibited DNA topoisomerase IV, suggesting complex mechanisms of actions for compounds in this series.
- Subjects :
- DNA Topoisomerase IV
Methicillin-Resistant Staphylococcus aureus
Chalcone
Stereochemistry
Flavonoid
Substituent
Chemistry Techniques, Synthetic
Microbial Sensitivity Tests
Phloroglucinol
Article
Structure-Activity Relationship
chemistry.chemical_compound
Minimum inhibitory concentration
Chalcones
Biosynthesis
Chlorocebus aethiops
Drug Discovery
Animals
Topoisomerase II Inhibitors
Structure–activity relationship
Mode of action
Vero Cells
chemistry.chemical_classification
Mycobacterium tuberculosis
Anti-Bacterial Agents
3. Good health
chemistry
Chromones
DNA Gyrase
Molecular Medicine
Macromolecule
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 57
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....c4db5e07550e7043455e95f863939b0f