PUBLICATION
Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents
- Authors
- Gunasekharan, M., Choi, T.I., Rukayadi, Y., Mohammad Latif, M.A., Karunakaran, T., Mohd Faudzi, S.M., Kim, C.H.
- ID
- ZDB-PUB-210911-4
- Date
- 2021
- Source
- Molecules 26(17): (Journal)
- Registered Authors
- Kim, Cheol-Hee
- Keywords
- anti-MRSA, molecular docking, pyrrolylated-chalcones, synthesis, zebrafish toxicity
- MeSH Terms
-
- Pyrroles/chemistry
- Pyrroles/pharmacology*
- Dose-Response Relationship, Drug
- Microbial Sensitivity Tests
- Chalcones/chemistry
- Chalcones/pharmacology*
- Methicillin-Resistant Staphylococcus aureus/drug effects*
- Molecular Structure
- Anti-Bacterial Agents/chemistry
- Anti-Bacterial Agents/pharmacology*
- Structure-Activity Relationship
- PubMed
- 34500755 Full text @ Molecules
Citation
Gunasekharan, M., Choi, T.I., Rukayadi, Y., Mohammad Latif, M.A., Karunakaran, T., Mohd Faudzi, S.M., Kim, C.H. (2021) Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents. Molecules. 26(17):.
Abstract
Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1-15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of -7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping