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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

Phylogenetic relationship between Penicillium radicum [SF] and other Penicillium sp. 2.
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f1: Phylogenetic relationship between Penicillium radicum [SF] and other Penicillium sp. 2.

Mentions: On the basis of morphological, cultural and physiological characteristics, the isolated strain was found to be closely related to ascomycetes (Table 1 and Fig. 1). This fungal strain was designated as SF and further identified on the basis of 18S rRNA homology studies and the sequence was submitted in the GenBank under accession no. KJ528407. A partial 18S rRNA gene sequence (1112 bp in length) of SF was compared with the sequences already available in the GenBank database through BLAST analysis and found to possess close similarity to some members of the class ascomycetes, like, Penicillium radicum (DQ891400.1), P. radicum (AY256855.1), P. variablie (AY3739393.1), P. islandicum (L14504.1) and Penicillium sp. Re 011124 (AB 080726.1) (Fig. 1). Finally, the neighbour-joining phylogenetic tree of the partial 18S rRNA sequence data confirmed that P. radicum (DQ891400.1) was most closely related to the strain SF with 100% sequence similarity (Fig. 1). Olive-green in coloured ellipsoidal conidia with roughened or spiral-striated walls (5 × 3.75 μm) were observed under scanning electron microscope (Supplementary Information: Figure SI1). The strain was submitted in Microbial Type Culture Collection (MTCC), Institute of Microbial Technology (IMTECH) (www.http://mtcc.imtech.res.in), Chandigarh, Punjab, India as Penicillium radicum MTCC 7584.


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)

Phylogenetic relationship between Penicillium radicum [SF] and other Penicillium sp. 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Phylogenetic relationship between Penicillium radicum [SF] and other Penicillium sp. 2.
Mentions: On the basis of morphological, cultural and physiological characteristics, the isolated strain was found to be closely related to ascomycetes (Table 1 and Fig. 1). This fungal strain was designated as SF and further identified on the basis of 18S rRNA homology studies and the sequence was submitted in the GenBank under accession no. KJ528407. A partial 18S rRNA gene sequence (1112 bp in length) of SF was compared with the sequences already available in the GenBank database through BLAST analysis and found to possess close similarity to some members of the class ascomycetes, like, Penicillium radicum (DQ891400.1), P. radicum (AY256855.1), P. variablie (AY3739393.1), P. islandicum (L14504.1) and Penicillium sp. Re 011124 (AB 080726.1) (Fig. 1). Finally, the neighbour-joining phylogenetic tree of the partial 18S rRNA sequence data confirmed that P. radicum (DQ891400.1) was most closely related to the strain SF with 100% sequence similarity (Fig. 1). Olive-green in coloured ellipsoidal conidia with roughened or spiral-striated walls (5 × 3.75 μm) were observed under scanning electron microscope (Supplementary Information: Figure SI1). The strain was submitted in Microbial Type Culture Collection (MTCC), Institute of Microbial Technology (IMTECH) (www.http://mtcc.imtech.res.in), Chandigarh, Punjab, India as Penicillium radicum MTCC 7584.

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