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Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum.

Singh V, Praveen V, Tripathi D, Haque S, Somvanshi P, Katti SB, Tripathi CK - Sci Rep (2015)

Bottom Line: In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains.Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins).We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow-226031, Uttar Pradesh, India.

ABSTRACT
During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability.

No MeSH data available.


Related in: MedlinePlus

Fermentation profile of Penicillium radicum.
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f2: Fermentation profile of Penicillium radicum.

Mentions: The growth and fermentation profile of SF (P. radicum) was evaluated in Potato dextrose broth (PDB) medium and results have been summarized in Fig. 2. The log phase was observed between 20–48 h and maximum biomass (5.5 g/L) was found at 48 h of the fungal growth. The production of the antifungal metabolite commenced in the late log phase of the fungal growth and accumulated maximum (110 mg/L) in the stationary phase (approximately 120 h of the incubation) and decreased slowly, afterwards. The pH of the production medium decreased slightly during the growth of the fungus, whereas in the production phase it was increased from 4.0 to 5.5, which suggests that the extracellular metabolites formed during the late log phase might be of basic nature, hence increased the pH of the medium.


Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum.

Singh V, Praveen V, Tripathi D, Haque S, Somvanshi P, Katti SB, Tripathi CK - Sci Rep (2015)

Fermentation profile of Penicillium radicum.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4498184&req=5

f2: Fermentation profile of Penicillium radicum.
Mentions: The growth and fermentation profile of SF (P. radicum) was evaluated in Potato dextrose broth (PDB) medium and results have been summarized in Fig. 2. The log phase was observed between 20–48 h and maximum biomass (5.5 g/L) was found at 48 h of the fungal growth. The production of the antifungal metabolite commenced in the late log phase of the fungal growth and accumulated maximum (110 mg/L) in the stationary phase (approximately 120 h of the incubation) and decreased slowly, afterwards. The pH of the production medium decreased slightly during the growth of the fungus, whereas in the production phase it was increased from 4.0 to 5.5, which suggests that the extracellular metabolites formed during the late log phase might be of basic nature, hence increased the pH of the medium.

Bottom Line: In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains.Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins).We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow-226031, Uttar Pradesh, India.

ABSTRACT
During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability.

No MeSH data available.


Related in: MedlinePlus