Pseudopyronine B: A Potent Antimicrobial and Anticancer Molecule Isolated from a Pseudomonas mosselii

Abstract

In continuation of our search for new bioactive compounds from soil microbes, a fluorescent Pseudomonas strain isolated from paddy field soil of Kuttanad, Kerala, India was screened for the production of bioactive secondary metabolites. This strain was identified as Pseudomonas mosselii through 16S rDNA gene sequencing followed by BLAST analysis and the bioactive metabolites produced were purified by column chromatography (silica gel) and a pure bioactive secondary metabolite was isolated. This bioactive compound was identified as Pseudopyronine B by NMR and HR-ESI-MS. Pseudopyronine B recorded significant antimicrobial activity especially against Gram-positive bacteria and agriculturally important fungi. MTT assay was used for finding cell proliferation inhibition, and Pseudopyronine B recorded significant antitumor activity against non-small cell lung cancer cell (A549), and mouse melanoma cell (B16F10). The preliminary MTT assay results revealed that Pseudopyronine B recorded both dose- and time-dependent inhibition of the growth of test cancer cell lines. Pseudopyronine B induced apoptotic cell death in cancer cells as evidenced by Acridine orange/ethidium bromide and Hoechst staining, and this was further confirmed by flow cytometry analysis using Annexin V. Cell cycle analysis also supports apoptosis by inducing G2/M accumulation in both A549 and B16F10 cells. Pseudopyronine B treated cells recorded significant up-regulation of caspase 3 activity. Moreover, this compound recorded immunomodulatory activity by enhancing the proliferation of lymphocytes. The production of Pseudopyronine B by P. mosselii and its anticancer activity in A549 and B16F10 cell lines is reported here for the first time. The present study has a substantial influence on the information of Pseudopyronine B from P. mosselii as potential sources of novel drug molecule for the pharmaceutical companies, especially as potent antimicrobial and anticancer agent.

Novel Pseudomonas Species Prevent the Growth of the Phytopathogenic Fungus Aspergillus flavus

“…Its significance lies in facilitating swarming motility and biofilm formation while exhibiting zoosporicidal and antifungal activities [ 70 ]. Another compelling cluster identified at the genome level was pseudopyronine A/pseudopyronine B, demonstrating potent activity against plant pathogenic fungi [ 71 ]. Moreover, the genomic cluster responsible for the lipopeptide viscosin production was also identified.…”

Discovery of Phloeophagus Beetles as a Source of Pseudomonas Strains That Produce Potentially New Bioactive Substances and Description of Pseudomonas bohemica sp. nov.

“…Several of the isolates obtained in this study appeared to be potential candidates to produce antimicrobial substances, being several strains identified as Pseudomonas some of the best antimicrobial producers, according to our screening. This genus is known to produce antimicrobials and other interesting bioactive compounds (Laine et al, 1996 ; Stintzi et al, 1996 ; Raaijmakers et al, 1997 ; Marinho et al, 2009 ; Bauer et al, 2015 ; Nishanth Kumar et al, 2016 ; Ganne et al, 2017 ). Based on that, strains Pseudomonas IA19 T , Pseudomonas A2-NA12, Pseudomonas A2-NA13 were selected for further analysis of their genetic potential to produce pharmaceutically interesting molecules by sequencing and mining their genomes.…”

“…This strain also displayed moderate inhibition of other Firmicutes ( Listeria welshimeri ) and Actinobacteria ( Micrococcus luteus, Arthrobacter crystallopoietes , and Corynebacterium xerosis ), as well as anti-leishmanial and algaecide activities (Bauer et al, 2015 ). Moreover, pseudopyronine B has also shown antitumoral activity (Nishanth Kumar et al, 2016 ). These compounds have been identified in different species of the genus Pseudomonas and in the genus Alteromonas (Bauer et al, 2015 ).…”

Efficacy of a series of alpha-pyrone derivatives against Leishmania (L.) infantum and Trypanosoma cruzi

“…Scheme 1. Synthesis of alkanoyl and alkyl pyrones (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Reagents and conditions: a) Acyl chloride (2.1 eq.…”

“…[10] Both alpha-and gammapyrones have been reported to exhibit biological properties including antitumor, antimicrobial and anti-HIV activities. [9][10][11] There are only a few reports describing the evaluation of the pyrone class of natural products for activity towards infectious diseases such as leishmaniasis and Chagas disease. For example, gamma-pyrones 1 and 2, isolated from the seeds of Podolepsis hieracioides (Asteraceae), exhibit in vitro antileishmanial activity in the micromolar range while kojic acid (3), isolated from Aspergillus fungi, demonstrates in vitro and in vivo antileishmanial efficacy (Figure 1).…”