title: Benzaldehyde Schiff bases regulation to the metabolism, hemolysis, and virulence genes expression in vitro and their structure-microbicidal activity relationship.
abstract: There is an urgent need to develop new antibacterial agents because of multidrug resistance by bacteria and fungi. Schiff bases (aldehyde or ketone-like compounds) exhibit intense antibacterial characteristics, and are therefore, promising candidates as antibacterial agents. To investigate the mechanism of action of newly designed benzaldehyde Schiff bases, a series of high-yielding benzaldehyde Schiff bases were synthesized, and their structures were determined by NMR and MS spectra data. The structure-microbicidal activity relationship of derivatives was investigated, and the antibacterial mechanisms were investigated by gene assays for the expression of functional genes in vitro using Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The active compounds were selective for certain active groups. The polar substitution of the R2 group of the amino acids in the Schiff bases, affected the antibacterial activity against E. coli and S. aureus; specific active group at the R3 or R4 groups of the acylhydrazone Schiff bases could improve their inhibitory activity against these three tested organisms. The antibacterial mechanism of the active benzaldehyde Schiff bases appeared to regulate the expression of metabolism-associated genes in E. coli, hemolysis-associated genes in B. subtilis, and key virulence genes in S. aureus. Some benzaldehyde Schiff bases were bactericidal to all the three strains and appeared to regulate gene expression associated with metabolism, hemolysis, and virulence, in vitro. The newly designed benzaldehyde Schiff bases possessed unique antibacterial activity and might be potentially useful for prophylactic or therapeutic intervention of bacterial infections.
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China; Guizhou University, Guiyang 550025, Guizhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China; The Second Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550003, Guizhou, China.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Xia
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China; Guizhou University, Guiyang 550025, Guizhou, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China.
authors.forename: Hua-Yong
authors.initials: HY
authors.lastname: Lou
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China.
authors.forename: Tang-Jingjun
authors.initials: TJ
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China. Electronic address: wdpan@163.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, Guizhou, China. Electronic address: luoheng71050@aliyun.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Luo
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D015394:Molecular Structure; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D014774:Virulence / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D001547:Benzaldehydes; D012545:Schiff Bases; C032175:benzaldehyde
keywords: Antibacterial activity; Benzaldehyde Schiff base; Regulating gene expression; Synthesis