Waste to drugs: identification of pyrolysis by-products as antifungal agents against Cryptococcus neoformans

Abstract

The fungi, Cryptococcus neoformans cause major infections such as cryptococcal meningitis and cryptococcosis. Therefore, we explored the use of Thioredoxin reductase (Trr1) from C. neoformans as a gene target for the development of novel antifungal agents. Trr1 plays an essential role in the survival in the oxidative environment of macrophages and is important for the virulence of C. neoformans. During the thermochemical conversion (pyrolysis) of lignocellulosic biomass (LCB), a cocktail of compounds is produced by the decomposition and degradation. In general, LCB-derived cocktail of compounds is a rich source of aromatic compounds that have been shown to be antifungal in nature. Usually, the aqueous phase produced during biomass pyrolysis is generally regarded as waste. Here, we used Parthenium hysterophorus biomass as the antifungal source and obtained the aqueous phase after pyrolysis. Using GC-MS analysis of the aqueous phase collected from P. hysterophorus biomass revealed the presence of a large number of aromatic and organic compounds. Using virtual screening, the compounds present in the aqueous phase were docked against Trr1 using GLIDE. Two promising candidates were analyzed further by performing molecular dynamics simulation using GROMACS, to establish stable interactions. We validated the computational results with clustering analysis. We report that 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl have a potent antifungal property and we postulate that they could be a potent antifungal agent against Trr1 of C. neoformans.

Communicated by Ramaswamy H. Sarma

Keywords:

• Biomass waste
• molecular docking
• antifungal
• molecular dynamics simulations
• pyrolysis

Acknowledgments

The authors gratefully acknowledged SASTRA Deemed University for research facility and infrastructure support.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

The research was funded by the TRR research scheme of SASTRA Deemed University. Authors Dr. Shanmugam S. R and Srividhya Krishnan sincerely thank DST for the financial support through INSPIRE grants DST/INSPIRE/04/2017/002528 and SASTRA START-UP grant. Dr. Ragothaman M. Yennamalli is supported by the UGC-Basic Science Research Startup Grant, University Grants Commission, Government of India (F.30-561/2021(BSR)) and National Agricultural Science Fund-Indian Council of Agricultural Research (NASF-ICAR), Government of India (F. No. NASF/SUTRA-02/2022-23/50). This work was supported by Department of Science and Technology, Ministry of Science and Technology, India.