Waste to drugs: identification of pyrolysis by-products as antifungal agents against Cryptococcus neoformans
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Published on: February 14, 2018
Srividhya Krishnan1,2, Krishnakant Gupta3, Subramaniyasharma Sivaraman1,2
1Department of Biotechnology, School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, India.
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.
Insights
Researchers identified potent antifungal compounds from plant waste. These compounds target Thioredoxin reductase (Trr1) in Cryptococcus neoformans, offering a novel strategy against fungal infections.
Area of Science:
- Mycology
- Biochemistry
- Computational Chemistry
Background:
- Cryptococcus neoformans causes serious infections like cryptococcal meningitis.
- Thioredoxin reductase (Trr1) is crucial for C. neoformans virulence and survival.
- Lignocellulosic biomass pyrolysis yields antifungal aromatic compounds.
Purpose of the Study:
- To identify novel antifungal agents targeting C. neoformans Trr1.
- To explore the potential of Parthenium hysterophorus pyrolysis aqueous phase as an antifungal source.
Main Methods:
- GC-MS analysis of P. hysterophorus pyrolysis aqueous phase.
- Virtual screening and molecular docking of identified compounds against C. neoformans Trr1 using GLIDE.
- Molecular dynamics simulations using GROMACS and clustering analysis for validation.
Main Results:
- GC-MS revealed numerous aromatic and organic compounds in the aqueous phase.
- 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl were identified as promising candidates.
- Computational analysis confirmed stable interactions of these compounds with C. neoformans Trr1.
Conclusions:
- Parthenium hysterophorus pyrolysis aqueous phase contains compounds with antifungal potential.
- 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl show promise as novel antifungal agents.
- These compounds represent a new therapeutic avenue against C. neoformans infections by targeting Trr1.
