Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves

Heba E Elsayed; Reem A Kamel; Reham R Ibrahim; Ahmed S Abdel-Razek; Mohamed A Shaaban; Marcel Frese; Norbert Sewald; Hassan Y Ebrahim; Fatma A Moharram

doi:10.3389/fchem.2021.760083

Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves

Front Chem. 2021 Oct 13:9:760083. doi: 10.3389/fchem.2021.760083. eCollection 2021.

Authors

Heba E Elsayed¹, Reem A Kamel², Reham R Ibrahim¹, Ahmed S Abdel-Razek³, Mohamed A Shaaban⁴, Marcel Frese⁵, Norbert Sewald⁵, Hassan Y Ebrahim¹, Fatma A Moharram¹

Affiliations

¹ Pharmacognosy Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt.
² Mansheyat El-Bakry General Hospital, Cairo, Egypt.
³ Microbial Chemistry Department, Genetic Engineering and Biotechnology Research Division, National Research Centre, Giza, Egyp.
⁴ Chemistry of Natural Compounds Department, Division of Pharmaceutical Industries, National Research Centre, Giza, Egypt.
⁵ Organic and Bio-organic Chemistry, Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.

Abstract

Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture of Aspergillus sp. retrieved from Tecoma stans (L.) Juss. ex Kunth leaves. Their anticancer and antimicrobial activities were evaluated in MTT and agar well diffusion assays, respectively. The cytotoxicity results showed that metabolite 3 displayed the best viability inhibition on the MCF-7 breast cancer cells with IC₅₀ = 225.21 µM, while 5 on the HepG2 hepatocellular carcinoma cells with IC₅₀ = 161.81 µM. 5 demonstrated a 60% apoptotic mode of cell death which is virtually correlated to its high docking affinity to Hsp90 ATP binding cleft (binding score -8.4 Kcal/mol). On the other side, metabolites 4 and 5 displayed promising antimicrobial activity especially on Pseudomonas aeruginosa with MIC = 125 μg/ml. The observed effect may be likely related to their excellent in silico inhibition of the bacterial DNA-gyrase kinase domain (binding score -10.28 Kcal/mol). To the best of our knowledge, this study is the first to report the promising cytotoxic and antibacterial activities of metabolites 3, 4, and 5 which needs further investigation and renovation to therapeutic leads.

Keywords: DNA-gyrase; Hsp90; anthraquinones; antimicrobial; aspergillus sp; cytotoxicity; xanthones.