Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach

Kumaravel Kaliaperumal; Limbadri Salendra; Yonghong Liu; Zhiran Ju; Sunil Kumar Sahu; Sanniyasi Elumalai; Kumaran Subramanian; Nahaa M Alotaibi; Nawaf Alshammari; Mohd Saeed; Rohini Karunakaran

doi:10.3389/fmicb.2023.1216928

Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach

Front Microbiol. 2023 Oct 2:14:1216928. doi: 10.3389/fmicb.2023.1216928. eCollection 2023.

Authors

Affiliations

¹ Unit of Biomaterials Division, Department of Orthodontics, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai, India.
² New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, Rutgers University, New Brunswick, NJ, United States.
³ Key Laboratory of Tropical Marine Bio-Resources and Ecology, Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
⁴ Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou, China.
⁵ State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources, Sun Yat-sen University, Guangzhou, China.
⁶ Department of Biotechnology, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
⁷ Research Department of Microbiology, Sri Sankara Arts and Science College (Autonomous), Kanchipuram, Tamil Nadu, India.
⁸ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
⁹ Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia.
¹⁰ Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong, Malaysia.
¹¹ Centre for Excellence for Biomaterials Science AIMST University, Semeling, Bedong, Malaysia.
¹² Department of Bioinformatics, Saveetha School of Engineering, Saveetha University, Chennai, India.

^# Contributed equally.

Abstract

Introduction: Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties.

Methods: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening.

Results: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC₅₀ concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain.

Discussion: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

Keywords: HL60; anticancer; averufin; cytotoxicity; environment; fungi; molecular docking; sponges.

Grants and funding

The authors express their gratitude to the Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R356), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.