Quinazolinone azolyl ethanols: potential lead antimicrobial agents with dual action modes targeting methicillin-resistant Staphylococcus aureus DNA.
OBJECTIVE
Due to bacterial drug resistance, a new series of quinazolinone azolyl ethanols were synthesized and evaluated.


RESULTS
In vitro antibacterial assay showed that triazolyl ethanol quinazolinone 3a was the most active compound, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimal inhibitory concentration value of 8 µg/ml, which was superior to chloromycin and comparable to norfloxacin. Molecular docking study displayed that compound 3a could interact with MRSA DNA by the formation of hydrogen bonds. Further interactions of quinazolinone 3a with MRSA DNA suggested that it could intercalate into MRSA DNA to form 3a-DNA complex. DNA cleavage properties of 3a-Cu2+and 3a-Zn2+complexes were confirmed by agarose gel electrophoresis experiments.


CONCLUSIONS
Compound 3a should be a potential lead antibacterial molecule with dual action modes.
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, China.
Xin-Mei
XM
Peng
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, China.
Li-Ping
LP
Peng
School of Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China.
Shuo
S
Li
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, China.
Srinivasa Rao
SR
Avula
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, China.
Vijaya Kumar
VK
Kannekanti
Drug Development Core, Faculty of Health Sciences, University of Macau, Macau, China.
Shao-Lin
SL
Zhang
Drug Development Core, Faculty of Health Sciences, University of Macau, Macau, China.
Kin Yip
KY
Tam
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, China.
Cheng-He
CH
Zhou
DNA cleavage; DNA intercalation; antibacterial; antifungal; imidazole; quinazolinone; triazole