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

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

doi:10.3389/fchem.2021.760083

Heba E Elsayed, Reham R Ibrahim + Show 7 more

Open Access

https://doi.org/10.3389/fchem.2021.760083

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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.

Highlights

Terrestrial plants are colonized by an infinite number of micro-organisms, denoted as endophytes (Uzma et al, 2018)
A pure colony of the endophytic fungus Aspergillus sp. was isolated from T. stans leaves and characterized based on its morphologic traits just as the diameter of the colonies (42–53 mm) after 7 days of incubation on potato dextrose agar (PDA) medium at 25°C, the deep green abundant smooth conidia with white mycelia, and the dark brown colour shown on the reverse (Figure 1A)
The ethyl acetate extract (EtOAc) of the rice culture of the isolated fungi exerts cytotoxic potential in a dose response manner in Microculture tetrazolium assay (MTT) assay with IC50 equivalent to 186.66 ± 9.4 and 158.54 ± 7.2 μg/ml on MCF-7 and HepG2 cell lines, respectively (Table 1)

Summary

Introduction

Terrestrial plants are colonized by an infinite number of micro-organisms, denoted as endophytes (Uzma et al, 2018). Endophytes are often bacteria or fungi that inhabit the internal plant tissues in a symbiotic relationship (Uzma et al, 2018). Such special co-existence afforded unique, structurally diverse metabolites. Some of which demonstrate potential biological activities as antimicrobial, Biological Activity of Aspergillus Metabolites antioxidant, anticancer, immunosuppressive, and antiinflammatory (Uzma et al, 2018; Keshri et al, 2021). Among the renowned fungal endophytes, is Aspergillus (Vadlapudi et al, 2017) which is considered a ubiquitous genus in the fungal kingdom and constitute near 185 species. Insights are directed to endophytes as alternate sources for the discovery of potent antimicrobial and anticancer agents

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