Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

Ann Med. 2022 Dec;54(1):2102-2114. doi: 10.1080/07853890.2022.2102205.

Abstract

Background: Penicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.

Methods: The metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.

Results: GC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4'-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml-1. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.

Conclusion: Metabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics. Key messagesThe first time explored complete metabolome through GC-MS and LC-MS-QTOF.Both in vivo & in vitro pharmacological investigation of P. claviforme.In silico molecular docking of LC-MS-QTOF metabolites.

Keywords: Penicillium claviforme; metabolic profiling; molecular docking; pharmacological activities.

MeSH terms

  • Analgesics / metabolism
  • Analgesics / pharmacology
  • Antioxidants* / pharmacology
  • Computational Biology
  • Humans
  • Molecular Docking Simulation
  • Penicillium* / metabolism

Substances

  • Analgesics
  • Antioxidants

Supplementary concepts

  • Penicillium vulpinum