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Limonoids from Melia azedarach Fruits as Inhibitors of Flaviviruses and Mycobacterium tubercolosis.

Sanna G, Madeddu S, Giliberti G, Ntalli NG, Cottiglia F, De Logu A, Agus E, Caboni P - PLoS ONE (2015)

Bottom Line: The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs.The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach.Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, Italy.

ABSTRACT
The biological diversity of nature is the source of a wide range of bioactive molecules. The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs. The present work was carried out to investigate the cytotoxicity, antiviral and antimycobacterial activity of the methanol extract and of four identified limonoids from the fruits of Melia azedarach (Meliaceae). The extract and purified limonoids were tested in cell-based assays for antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses and against Mycobacterium tuberculosis. Very interestingly, 3-α-tigloyl-melianol and melianone showed a potent antiviral activity (EC50 in the range of 3-11μM) against three important human pathogens, belonging to Flaviviridae family, West Nile virus, Dengue virus and Yellow Fever virus. Mode of action studies demonstrated that title compounds were inhibitors of West Nile virus only when added during the infection, acting as inhibitors of the entry or of a very early event of life cycle. Furthermore, 3-α-tigloyl-melianol and methyl kulonate showed interesting antimycobacterial activity (with MIC values of 29 and 70 μM respectively). The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach. They are known as cytotoxic compounds against different cancer cell lines, while their potential as antiviral and antibacterial was poorly investigated. Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need.

No MeSH data available.


Related in: MedlinePlus

Yield reduction assay.2A. Reduction of WNV titre in presence of not cytotoxic concentrations of melianone (20μM) and 3-tigloyl-melianol (15μM). 2’-C-methylguanosine was used as reference compound (at 4μM). 2B. The BHK-21 monolayers treated with the above compounds did not show significant cytopathic effects at the tested concentrations.
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pone.0141272.g002: Yield reduction assay.2A. Reduction of WNV titre in presence of not cytotoxic concentrations of melianone (20μM) and 3-tigloyl-melianol (15μM). 2’-C-methylguanosine was used as reference compound (at 4μM). 2B. The BHK-21 monolayers treated with the above compounds did not show significant cytopathic effects at the tested concentrations.

Mentions: The potential virucidal activity of 4 and 5 was investigated, incubating a WNV solution containing 5x105 PFU/ml for 45 min. at 37°C with two concentrations of each compound (6 and 20μM for 4; 20 and 50μM for 5). Tested compounds failed to affect the WNV infectivity (Fig 1), suggesting that the inhibition of WNV replication observed in cell-based assays is not due to the inactivation of virions, but can be totally attributed to an interference of compounds with the viral life cycle. The antiviral activity of 4 and 5 was further evaluated in an yield reduction assay, in order to demonstrate the reduction of virus titre in presence of two active compounds, during a single round of viral infection. Not cytotoxic concentrations of respectively 20 μM for 5 and 15μM for 4 were used; a reduction of virus titre was observed for both compounds (Fig 2).


Limonoids from Melia azedarach Fruits as Inhibitors of Flaviviruses and Mycobacterium tubercolosis.

Sanna G, Madeddu S, Giliberti G, Ntalli NG, Cottiglia F, De Logu A, Agus E, Caboni P - PLoS ONE (2015)

Yield reduction assay.2A. Reduction of WNV titre in presence of not cytotoxic concentrations of melianone (20μM) and 3-tigloyl-melianol (15μM). 2’-C-methylguanosine was used as reference compound (at 4μM). 2B. The BHK-21 monolayers treated with the above compounds did not show significant cytopathic effects at the tested concentrations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612778&req=5

pone.0141272.g002: Yield reduction assay.2A. Reduction of WNV titre in presence of not cytotoxic concentrations of melianone (20μM) and 3-tigloyl-melianol (15μM). 2’-C-methylguanosine was used as reference compound (at 4μM). 2B. The BHK-21 monolayers treated with the above compounds did not show significant cytopathic effects at the tested concentrations.
Mentions: The potential virucidal activity of 4 and 5 was investigated, incubating a WNV solution containing 5x105 PFU/ml for 45 min. at 37°C with two concentrations of each compound (6 and 20μM for 4; 20 and 50μM for 5). Tested compounds failed to affect the WNV infectivity (Fig 1), suggesting that the inhibition of WNV replication observed in cell-based assays is not due to the inactivation of virions, but can be totally attributed to an interference of compounds with the viral life cycle. The antiviral activity of 4 and 5 was further evaluated in an yield reduction assay, in order to demonstrate the reduction of virus titre in presence of two active compounds, during a single round of viral infection. Not cytotoxic concentrations of respectively 20 μM for 5 and 15μM for 4 were used; a reduction of virus titre was observed for both compounds (Fig 2).

Bottom Line: The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs.The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach.Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, Italy.

ABSTRACT
The biological diversity of nature is the source of a wide range of bioactive molecules. The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs. The present work was carried out to investigate the cytotoxicity, antiviral and antimycobacterial activity of the methanol extract and of four identified limonoids from the fruits of Melia azedarach (Meliaceae). The extract and purified limonoids were tested in cell-based assays for antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses and against Mycobacterium tuberculosis. Very interestingly, 3-α-tigloyl-melianol and melianone showed a potent antiviral activity (EC50 in the range of 3-11μM) against three important human pathogens, belonging to Flaviviridae family, West Nile virus, Dengue virus and Yellow Fever virus. Mode of action studies demonstrated that title compounds were inhibitors of West Nile virus only when added during the infection, acting as inhibitors of the entry or of a very early event of life cycle. Furthermore, 3-α-tigloyl-melianol and methyl kulonate showed interesting antimycobacterial activity (with MIC values of 29 and 70 μM respectively). The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach. They are known as cytotoxic compounds against different cancer cell lines, while their potential as antiviral and antibacterial was poorly investigated. Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need.

No MeSH data available.


Related in: MedlinePlus