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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

Effect of melianone and 3-α-tigloyl-melianol on WNV adsorption kinetic.BHK-21 cells were incubated during 0, 15, 30 and 60 min. at 4°C with WNV in the absence or presence of compounds. Each value represents a mean of duplicate assays. Treatment with both compounds doesn’t reduce the virus titre.
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pone.0141272.g004: Effect of melianone and 3-α-tigloyl-melianol on WNV adsorption kinetic.BHK-21 cells were incubated during 0, 15, 30 and 60 min. at 4°C with WNV in the absence or presence of compounds. Each value represents a mean of duplicate assays. Treatment with both compounds doesn’t reduce the virus titre.

Mentions: To better define the process of inhibition, the kinetics of virus adsorption in the presence of compounds was finally evaluated. As a matter of fact, low-temperature treatment allows binding of WNV to the cell surface receptors but prevents the internalization of virus particles into the cells [35,36]. BHK cells were incubated with WNV (m.o.i. = 1) and compounds for different times at 4°C, using 15μM for 4 and 20μM for 5. Results reported in Fig 4 show that the treatment with both compounds doesn’t reduce the virus titre in comparison to untreated infected control, suggesting that inhibition occurs after the adsoption step.


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)

Effect of melianone and 3-α-tigloyl-melianol on WNV adsorption kinetic.BHK-21 cells were incubated during 0, 15, 30 and 60 min. at 4°C with WNV in the absence or presence of compounds. Each value represents a mean of duplicate assays. Treatment with both compounds doesn’t reduce the virus titre.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0141272.g004: Effect of melianone and 3-α-tigloyl-melianol on WNV adsorption kinetic.BHK-21 cells were incubated during 0, 15, 30 and 60 min. at 4°C with WNV in the absence or presence of compounds. Each value represents a mean of duplicate assays. Treatment with both compounds doesn’t reduce the virus titre.
Mentions: To better define the process of inhibition, the kinetics of virus adsorption in the presence of compounds was finally evaluated. As a matter of fact, low-temperature treatment allows binding of WNV to the cell surface receptors but prevents the internalization of virus particles into the cells [35,36]. BHK cells were incubated with WNV (m.o.i. = 1) and compounds for different times at 4°C, using 15μM for 4 and 20μM for 5. Results reported in Fig 4 show that the treatment with both compounds doesn’t reduce the virus titre in comparison to untreated infected control, suggesting that inhibition occurs after the adsoption step.

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