title: Impaired ergosterol biosynthesis mediated fungicidal activity of Co(II) complex with ligand derived from cinnamaldehyde.
abstract: In this study, we have used aldehyde function of cinnamaldehyde to synthesize N, N'-Bis (cinnamaldehyde) ethylenediimine [C20H20N2] and Co(II) complex of the type [Co(C40H40N4)Cl2]. The structures of the synthesized compounds were determined on the basis of physiochemical analysis and spectroscopic data ((1)H NMR, FTIR, UV-visible and mass spectra) along with molar conductivity measurements. Anticandidal activity of cinnamaldehyde its ligand [L] and Co(II) complex was investigated by determining MIC80, time-kill kinetics, disc diffusion assay and ergosterol extraction and estimation assay. Ligand [L] and Co(II) complex are found to be 4.55 and 21.0 folds more efficient than cinnamaldehyde in a liquid medium. MIC80 of Co(II) complex correlated well with ergosterol inhibition suggesting ergosterol biosynthesis to be the primary site of action. In comparison to fluconazole, the test compounds showed limited toxicity against H9c2 rat cardiac myoblasts. In confocal microscopy propidium iodide (PI) penetrates the yeast cells when treated with MIC of metal complex, indicating a disruption of cell membrane that results in imbibition of dye. TEM analysis of metal complex treated cells exhibited notable alterations or damage to the cell membrane and the cell wall. The structural disorganization within the cell cytoplasm was noted. It was concluded that fungicidal activity of Co(II) complex originated from loss of membrane integrity and a decrease in ergosterol content is only one consequence of this.
authors.affiliation: Oral Microbiology Laboratory, Faculty of Dentistry, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait. Electronic address: sheikh@hsc.edu.kw.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Shreaz
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, P.O. Box 30002, Al Madinah Al Munawarrah, Saudi Arabia.
authors.forename: Rayees A
authors.initials: RA
authors.lastname: Shiekh
authors.affiliation: Department of Applied Sciences & Humanities, Jamia Millia Islamia (A Central University), P.O. Box 110025, New Delhi, India.
authors.forename: Vaseem
authors.initials: V
authors.lastname: Raja
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310, UTM, Skudai, Johor, Malaysia.
authors.forename: Waseem A
authors.initials: WA
authors.lastname: Wani
authors.affiliation: Oral Microbiology Laboratory, Faculty of Dentistry, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait.
authors.forename: Jawad M
authors.initials: JM
authors.lastname: Behbehani
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D004875:Ergosterol / Q000096:biosynthesis*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D008024:Ligands; D046529:Microscopy, Electron, Transmission; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D005659:Fungicides, Industrial; D008024:Ligands; D003035:Cobalt; D000171:Acrolein; C012843:cinnamaldehyde; D004875:Ergosterol
keywords: Anticandidal activity; Candida; Cinnamaldehyde; Co(II) complex; Ergosterol biosynthesis