Comprehensive Report
Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents
Yi-Xin Wang,
Zhao Deng,
Aisha Bibi,
Bo Fang,
Cheng-He Zhou,
Yi-Xin Wang
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorZhao Deng
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorAisha Bibi
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Bo Fang
College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing, 402160 China
E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Cheng-He Zhou
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
E-mail: [email protected], [email protected]Search for more papers by this authorYi-Xin Wang,
Zhao Deng,
Aisha Bibi,
Bo Fang,
Cheng-He Zhou,
Yi-Xin Wang
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorZhao Deng
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorAisha Bibi
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Bo Fang
College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing, 402160 China
E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Cheng-He Zhou
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715 China
E-mail: [email protected], [email protected]Search for more papers by this authorComprehensive Summary
A type of unique azole-hybridized acylhydrazonyl aloe emodins (AAEs) were developed as new antibacterial agents for combating bacterial infections. Some target AAEs showed strong antibacterial activities, especially, tetrazolylthioether AAE 27a exhibited broad antibacterial spectrum with 16—256 folds and 8—64 folds more active antibacterial efficacy than the reference drugs aloe emodin and norfloxacin, respectively. Tetrazolylthioether AAE 27a also gave low hemolysis and cytotoxicity, as well as favorable bioavailability. Preliminary mechanism explorations revealed that tetrazolylthioether AAE 27a could cause bacterial membrane depolarization and damage the cell membrane, resulting in nucleic acid leakage. Moreover, compound 27a could intercalate into DNA to impede its replication and form supramolecular 27a-DNA gyrase complex to disturb the function of DNA gyrase. These findings would provide valuable insights for the further exploration of azolyl acylhydrazonyl aloe emodins as new potential antibacterial candidates.
Supporting Information
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Appendix S1: Supporting Information |
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