Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents

Abstract

Comprehensive SummaryA 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.

A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates

“…The energy gap (Δ E ) of HOMO and LUMO helps to describe the chemical reactivity of the molecule. A smaller energy gap between these orbitals indicates a more facile transition and higher molecular reactivity, which is conducive to the interaction with the target. − The Frontier molecular orbitals for the compounds are graphically depicted in Table . The diagrams clearly illustrate the distribution of charge throughout the molecular system.…”

Cyanomethylquinolones as a New Class of Potential Multitargeting Broad-Spectrum Antibacterial Agents

“…In addition to the increase in membrane permeability, cell membrane damage was anticipated to result in the leakage of cellular contents, which was also important evidence of membrane damage. , Herein, the nucleic acid leakage was measured through monitoring the optical density values at 260 nm of the treated bacteria. As shown in Figure , the OD values presented remarkable amplification as the administration of these active CQs 15 and 41 and the carboxyl analogue 42c and fused CQ 41 caused more leakage of nucleic acid than the other two active compounds.…”