Inhibition of Aspergillus fumigatus Biofilm and Cytotoxicity Study of Natural Compound Cis-9-Hexadecenal

Abstract

Clinical limitations and drug-resistance are the basis of the search for new antifungal therapeutics against biofilm forming pathogen Aspergillus fumigatus. Cis-9-hexadecenal is a natural compound present in various plants extracts, but its antifungal activity against A. fumigatus is still unexplored. The aim of present study was to evaluate the antifungal efficacy of cis-9-hexadecenal on A. fumigatus, specifically its biofilm and to assess its cytotoxicity. Broth micro-dilution method revealed that cis-9hexadecenal inhibited 90% of planktonic growth of A. fumigatus at 0.078 mg/ml. In-vitro combinatorial effect between drug amphotericin B and cis-9-hexadecenal was studied by checkerboard assay. Cis-9-hexadecenal, in combination to amphotericin-B had additive effect and showed enhanced drug efficacy against A. fumigatus. The effect of cis-9-hexadecenal on pre-formed biofilm was analyzed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scanning electron microscopy. In MTT assay, minimum biofilm-eradicating concentration-80 of cis-9-hexadecenal was 0.156 mg/ml. Scanning electron micrograph showed absence of extracellular matrix and tangled hyphae in cis-9-hexadecenal treated biofilm whereas these structures were present in both untreated and amphotericin-B treated biofilm. Drug-likeness was predicted through in-silico ADMET studies. The study envisaged that cis-9-hexadecenal followed Lipinski's rule but had a higher Log P value indicating that it's not hydrophilic. The compound can be modified to enhance the absorption and permeation. Cell cytotoxicity study exhibited that cis-9-hexadecenal was not toxic to normal human lung epithelial cell line L-132 upto 0.62 mg/ml. The study concluded that cis-9-hexadecenal might be explored further as a potential therapeutic molecule for A. fumigatus associated diseases.

Isoeugenol affects expression pattern of conidial hydrophobin gene RodA and transcriptional regulators MedA and SomA responsible for adherence and biofilm formation in Aspergillus fumigatus

“…The biofilm of A. fumigatus was cultured in a 12-well polystyrene plate at calculated IC 50 of isoeugenol to analyse its effect (Manavathu et al 2014 ). To check biofilm eradication property of isoeugenol, biofilm was fully grown on 12-well polystyrene plate for 48 h and then, treated with IC 50 of isoeugenol for another 24 h (Hoda et al 2019 ; Sav et al 2018 ). To visualise the effect of isoeugenol, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were performed and samples were processed as described by González-Ramírez et al ( 2016 ), with minor modifications.…”

In-silico screening of plant-derived antivirals against main protease, 3CLpro and endoribonuclease, NSP15 proteins of SARS-CoV-2

“…The qualitative measurement of absorption, distribution, metabolism, excretion, and toxicity profile of selected compounds were predicted by using SwissADME program ( http://www.swissadme.ch/index.php ) (Hoda et al., 2019 ). The major ADME-Tox properties parameters include Molecular weight, H-bond acceptor, H-bond donors, Predicted octanol/water partition coefficient (MLogP), Total Polar Surface Area (TPSA), Lipinski (drug likeness), GI absorption, BBB permeant, Bioavailability score.…”

cis-9-Hexadecenal, a Natural Compound Targeting Cell Wall Organization, Critical Growth Factor, and Virulence of Aspergillus fumigatus

“…The computational study has reported C-9-H as a stable compound at varied conditions. 17 In the docking analysis, low binding energy of −4.95 kcal/mol was observed which was stabilized by hydrophobic interaction and hydrogen bond between C-9-H and the amino acid residues of PKS protein. The hydrogen bonds were formed at Thr-264 and Ser 171 residue of PKS active domain ( Figure 10).…”

“…18 It has been observed that C-9-H inhibited biofilm formation in A. fumigatus and was not cytotoxic to human normal lung epithelial cell line L-132. 17 ADME/Tox study has also revealed that C-9-H is a stable compound at varied physiological conditions and is safe for human consumption. 17 It has been described as an aliphatic long-chain volatile compound that helps in fatty acid degradation and has characteristic strong fragrance.…”

“…17 ADME/Tox study has also revealed that C-9-H is a stable compound at varied physiological conditions and is safe for human consumption. 17 It has been described as an aliphatic long-chain volatile compound that helps in fatty acid degradation and has characteristic strong fragrance. 19 It has also been used in the synthesis of lipidized-soluble and longacting insulin to enhance its hypoglycaemic effect.…”