Antimicrobial, antiproliferative activities and molecular docking of metabolites from Alternaria alternata

• Published in: AMB Express Vol. 13; no. 1; p. 68
• Main Authors: Khazaal, Heba T., Khazaal, Mohamed T., Abdel-Razek, Ahmed S., Hamed, Ahmed A., Ebrahim, Hassan Y., Ibrahim, Reham R., Bishr, Mokhtar, Mansour, Yara E., El Dib, Rabab A., Soliman, Hesham S. M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 06.07.2023; Springer Nature B.V; SpringerOpen
• Subjects: Acetic acid; Adenocarcinoma; Alternaria; Alternaria alternata; Antibacterial activity; Antibacterial materials; Antimicrobial activity; Antimicrobial agents; Antiproliferatives; Binding sites; Bioactive compounds; Biomedical and Life Sciences; Biotechnology; Colocasia esculanta leaves; Dimers; DNA topoisomerase; E coli; Efflux; Endophytes; Ergosterol; Ethyl acetate; Fungi; Human prostatic adenocarcinoma; Hydrophobicity; Leaves; Life Sciences; Metabolites; Microbial Genetics and Genomics; Microbiology; Molecular docking; NMR; Nuclear magnetic resonance; Original; Original Article; Phenylalanine; Propagation; Prostate cancer; Tumor cell lines; Antimicrobial activity; leaves; Molecular docking; Human prostatic adenocarcinoma; Colocasia esculanta leaves; Alternaria alternata
• ISSN: 2191-0855; 2191-0855
• DOI: 10.1186/s13568-023-01568-1

Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), β -Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements. The ethyl acetate extract, as well as compounds 1, 3, 4 and 6 were evaluated for their antimicrobial activity using agar well-diffusion and broth microdilution assays. Molecular docking study was carried out to explore the pharmacophoric moieties that governed the binding orientation of antibacterial active compounds to multidrug efflux transporter AcrB and the ATP binding site to E. coli DNA gyrase using MOE software. Results revealed that the most active antibacterial compounds 4 and 6 bind with high affinity in the phenylalanine-rich cage and are surrounded with other hydrophobic residues. The antiproliferative activity of all isolated compounds was in vitro evaluated using the human prostatic adenocarcinoma cell lines DU-145, PC-3, PC-3 M, 22Rv1 and CWR-R1ca adopting MTT assay. Compound 4 was the most active against almost all tested cell lines, with IC 50 values 28.6, 21.6, 17.1 and 13.3 against PC-3, PC-3 M, 22Rv1 and CWR-R1ca cell lines, respectively. Graphical Abstract Key points Characterization of Alternaria alternata HE11 strain from Colocasia esculenta leaves First isolation of three dimeric naphtho-γ-pyrones from genus Alternaria Fonsecinone A and Asperpyrone B showed significant anti-prostate cancer and antibacterial activity, respectively