Metabolic and pharmacological profiling of <i>Penicillium claviforme</i> by a combination of experimental and bioinformatic approaches
Creators: name: Shah, Zafar Ali
name: Khan, Khalid
name: Iqbal, Zafar
name: Masood, Tariq
name: Hemeg, Hassan A.
name: Rauf, Abdur
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Physiology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: <i>Penicillium</i> produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of <i>Penicillium claviforme</i> (<i>P. claviforme</i>) (FBP-DNA-1205) was studied alongside pharmacological research in this study. The metabolic profile of <i>P. claviforme</i> 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 <i>in vitro</i> model was utilised to study the cytotoxic and antioxidant activities, while an <i>in vivo</i> model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis. 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 <i>P. claviforme</i> displayed significant cytotoxic activity <i>in vitro</i>, with an LD50 value of 92.22 µgml<sup>−1</sup>. The antinociceptive effects <i>in vivo</i> were dose-dependent significantly (<i>p</i> &lt; .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 <i>in silico</i> model. Metabolic profile of <i>P. claviforme</i> shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, <i>P. claviforme</i> exhibits substantial antioxidant and cytotoxic activities in an <i>in vitro</i> model as well as antinociceptive activity in an <i>in vivo</i> 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 <i>in vivo</i> &amp; <i>in vitro</i> pharmacological investigation of <i>P. claviforme</i>.<i>In silico</i> molecular docking of LC-MS-QTOF metabolites. The first time explored complete metabolome through GC-MS and LC-MS-QTOF. Both <i>in vivo</i> &amp; <i>in vitro</i> pharmacological investigation of <i>P. claviforme</i>. <i>In silico</i> molecular docking of LC-MS-QTOF metabolites.