Limonoids from Melia azedarach Fruits as Inhibitors of Flaviviruses and Mycobacterium tubercolosis.
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.
Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, Italy.
Giuseppina
G
Sanna
Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, Italy.
Silvia
S
Madeddu
Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, Italy.
Gabriele
G
Giliberti
Department of Life and Environmental Sciences, High Resolution Mass Spectrometry Laboratory, University of Cagliari, Italy.
Nikoletta G
NG
Ntalli
Department of Life and Environmental Sciences, High Resolution Mass Spectrometry Laboratory, University of Cagliari, Italy.
Filippo
F
Cottiglia
Department of Life and Environmental Sciences, Section of Medical Microbiology, University of Cagliari, Italy.
Alessandro
A
De Logu
Department of Life and Environmental Sciences, Section of Medical Microbiology, University of Cagliari, Italy.
Emanuela
E
Agus
Department of Life and Environmental Sciences, High Resolution Mass Spectrometry Laboratory, University of Cagliari, Italy.
Pierluigi
P
Caboni
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D005416:Flavivirus / Q000187:drug effects*; D018177:Flavivirus Infections / Q000188:drug therapy / Q000821:virology; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031586:Melia azedarach / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D036701:Limonins; D010936:Plant Extracts