SOD inhibitors research from endophytics fungi extracts

Superoxide Dismutase (SOD) inhibito"rs are proven to be very interesting leads to cancer treatment and cisplatine resistance reversion [1]. The Nature is a huge “pot of gold” for new molecules research and among the living organisms; fungal endophytes represent an interesting renewable source of new compounds as their chemical investigation is quite recent in comparison to other organisms. In this study we investigated endophytes isolated from Amazonian plants, cultured on Malt-Agar medium and extracted by EtOAc. An in vitro enzymatic test, reproducible, fast and well adapted for fast-screening research of SOD inhibitors was developed in our research group. This method, based on pyrogallol colorimetric properties [2] allows to highlight both the anti-oxidant properties of extracts and their ability to inhibit the SOD. The preliminary results show an anti-SOD activity in 16 on 57 endophytic fungi extracts. In order to decipher putative active compounds on our SOD assay model, a dereplication strategy based on LC-HRMS profiling was undertaken. The most active strain, bellowing the Pestalotiopsis genus (20% inhibition of SOD activity), was selected and a LC-MS profile of this sample was performed in order to find furocoumarins moieties since benzopyranoids scaffold are potential inhibitors of SOD as shown by few reports [3]. A [M+H]⁺ ions at 235.096 compound, corresponding with aloesol, a coumarine derivative already identified in Pestalotiopsis genus [4], was found in our sample, as well as a lot of other furocoumarines moieties. We are now targeting the isolation and the purification of these compounds, to experience our hypothesis.

In conclusion, we confirmed that the pyrogallol test is indeed a good indicator for the SOD activity of natural samples, because its results match with bibliography. Moreover, we found new compound(s) responsible for anti-SOD activity, what provide a huge hope for cancer and parasitosis treatment.

Keywords: SuperOxide Dismutase, endophytes, metabolomic.

References:

[1] Papa L, Manfredi G, Germain D. SOD1, an unexpected novel target for cancer therapy. Genes Cancer 2014; 5:15 – 21

[2] Li X. Improved pyrogallol autoxidation method: a reliable and cheap superoxide scavenging assay suitable for all antioxidants. J Agric Food Chem 2012; 60: 6418 – 6424

[3] Raja SB, Murali MR, Roopa K, Devaraj SN. Imperatorin a furocoumarin inhibits periplasmic Cu-Zn SOD of Shigella dysenteriae their by modulates its resistance towards phagocytosis during host pathogen interaction. Biomed Pharmacother 2011; 65: 560 – 568

[4] Yang XL, Huang L, Li HY, Yang DF, Li ZZ. Two new compounds from the plant endophytic fungus Pestalotiopsis versicolor. J Asian Nat Prod Res 2015; 17: 333 – 337.