Antimalarial secondary metabolites from Morinda lucida
- Authors: Chithambo, Bertha
- Date: 2017
- Subjects: Botanical chemistry , Anthraquinones , Antimalarials , Rubiaceae -- Therapeutic use , Malaria -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/45730 , vital:25535
- Description: Antimalarial activities of secondary metabolites from Morinda lucida (Rubiaceae), were investigated. Even though M. lucida is traditionally used to treat malaria, diabetes, jaundice, hypertension, dysentery and many other diseases, the compounds in this plant have not yet been fully investigated and characterised. Most of the studies that have been done on this plant focused on the medicinal properties of the crude extracts but have not gone further to isolate and characterise the compounds. In this study, the methanol - dichloromethane crude extract from the bark of M. lucida was fractionated into fractions 1-8. Fractions 2-5 were purified in order to isolate active secondary metabolites. The isolated pure compounds were characterised and identified. An in vitro antimalarial assay was carried out on the crude extract, fractions, pure compounds and solutions made from different combinations of pure compounds using the parasite lactate dehydrogenase (pLDH) assay. An IC50 done on the methanolic crude extract gave a value of 25 µg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Each of the pure compounds tested had very little activity. Their activities were increased when samples from the different compounds were mixed. One of these mixtures reduced malaria viability to about 22 % at 20 µM and gave an IC50 value of 17 µM. Antibacterial assays were also carried out on the crude extract and fractions. Fractions 2 and 3 were relatively active (MIC values ranging between 125-1000 µg/mL) against M. cattarhalis and E. faecalis. Fraction 2 was also the most active on S. typhimurium and S. aureus (MIC value of 1000 µg/mL) compared with the other fractions. This same fraction also showed some activity against M. tuberculosis with MIC90 and MIC99 values of 40.9 and 46.3 µg/mL respectively in an anti-tuberculosis assay.The following compounds, comprising of iridoids (asperuloside and asperulosidic acid), terpenoids (stigmasterol, P-sitosterol, campesterol, lanosterol and cycloartenol) and anthraquinones [5,15-O-dimethylmorindol, 1,7-dihydroxy-2-methoxy-5-(methoxymethyl) anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone], were isolated. All these compounds have been isolated from different plants before with the exception of 1,7-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone which were tentatively assigned the structures due to insufficient data. To the best of our knowledge, this is the first report on the identification of all of the mentioned compounds, with the exception of ß-sitosterol and stigmasterol, from M. lucida. Molecular docking was performed on one of the isolated anthraquinones (5,15-O- dimethylmorindol) to check if it can bind to cytochrome bci, a known target for atovaquone. This compound interacted with the same amino acids that atovaquone, a well known antimalarial agent, interacted with on cytochrome bc1 indicating a possible similar mode of action.
- Full Text:
- Date Issued: 2017
- Authors: Chithambo, Bertha
- Date: 2017
- Subjects: Botanical chemistry , Anthraquinones , Antimalarials , Rubiaceae -- Therapeutic use , Malaria -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/45730 , vital:25535
- Description: Antimalarial activities of secondary metabolites from Morinda lucida (Rubiaceae), were investigated. Even though M. lucida is traditionally used to treat malaria, diabetes, jaundice, hypertension, dysentery and many other diseases, the compounds in this plant have not yet been fully investigated and characterised. Most of the studies that have been done on this plant focused on the medicinal properties of the crude extracts but have not gone further to isolate and characterise the compounds. In this study, the methanol - dichloromethane crude extract from the bark of M. lucida was fractionated into fractions 1-8. Fractions 2-5 were purified in order to isolate active secondary metabolites. The isolated pure compounds were characterised and identified. An in vitro antimalarial assay was carried out on the crude extract, fractions, pure compounds and solutions made from different combinations of pure compounds using the parasite lactate dehydrogenase (pLDH) assay. An IC50 done on the methanolic crude extract gave a value of 25 µg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Each of the pure compounds tested had very little activity. Their activities were increased when samples from the different compounds were mixed. One of these mixtures reduced malaria viability to about 22 % at 20 µM and gave an IC50 value of 17 µM. Antibacterial assays were also carried out on the crude extract and fractions. Fractions 2 and 3 were relatively active (MIC values ranging between 125-1000 µg/mL) against M. cattarhalis and E. faecalis. Fraction 2 was also the most active on S. typhimurium and S. aureus (MIC value of 1000 µg/mL) compared with the other fractions. This same fraction also showed some activity against M. tuberculosis with MIC90 and MIC99 values of 40.9 and 46.3 µg/mL respectively in an anti-tuberculosis assay.The following compounds, comprising of iridoids (asperuloside and asperulosidic acid), terpenoids (stigmasterol, P-sitosterol, campesterol, lanosterol and cycloartenol) and anthraquinones [5,15-O-dimethylmorindol, 1,7-dihydroxy-2-methoxy-5-(methoxymethyl) anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone], were isolated. All these compounds have been isolated from different plants before with the exception of 1,7-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone which were tentatively assigned the structures due to insufficient data. To the best of our knowledge, this is the first report on the identification of all of the mentioned compounds, with the exception of ß-sitosterol and stigmasterol, from M. lucida. Molecular docking was performed on one of the isolated anthraquinones (5,15-O- dimethylmorindol) to check if it can bind to cytochrome bci, a known target for atovaquone. This compound interacted with the same amino acids that atovaquone, a well known antimalarial agent, interacted with on cytochrome bc1 indicating a possible similar mode of action.
- Full Text:
- Date Issued: 2017
Characterisation, antimalarial and biological activities of secondary metabolites from leaves of anonidium mannii
- Authors: Makoni, Pfungwa Gervase
- Date: 2017
- Subjects: Anonidium mannii -- Therapeutic use , Botanical chemistry , Annonaceae -- Therapeutic use , Apocynaceae -- Therapeutic use , Malaria -- Chemotherapy , Tuberculosis -- Chemotherapy , Bacterial diseases -- Chemotherapy , Cancer -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4797 , vital:20725
- Description: Anonidium mannii is a plant of the Annonaceae genus which is used traditionally in Africa for the treatment of gonorrhoea, malaria, cancer, skin inflammation and dysentery. In this study we will evaluate antimalarial, antifungal, anti - tuberculosis, antibacterial activities and cytotoxicity of different fractions in order to provide a scientific rationale for the traditional use of Anonidium mannii as well as provide possible novel drugs in the treatment of multi drug resistant strains of parasites and bacteria. Extracts from dried leaves were obtained by using solvent extraction and different fractions obtained using column chromatography eluted with solvents of varying polarities to obtain a wide range of metabolites. The antimalarial activity of the various fractions and some pure compounds was evaluated using plasmodium lactate dehydrogenase (pLDH) assay. Cytotoxicity was evaluated using HeLa cells while anti – tuberculosis assay was evaluated using the green fluorescent protein. Antibacterial activity of the extracts was evaluated using micro-dilution assay against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) bacteria and Gram-negative (Escherichia coli and Salmonella typhi) bacteria. Antifungal activity was evaluated against Candida albicans. The antimalarial assays yielded some fractions with promising IC50 values. The selected fractions yielded activities ranging between 0.73 μg/mL and 20.23 μg/mL. The fraction with the best activity was obtained from a hexane/ethyl acetate fraction. AM1C, a cholestane, showed the best activity from the pure metabolites that were screened. AM3C, stigmasterol, a pure compound gave the best antifungal activity with an MIC of 0.063 μg/mL. AM9C another pure compound (sterol) showed the best activity against S. typhi with a value of 0.031 μg/mL. AM2C a pure compound showed an activity of 0.063 μg/mL against E. faecalis. The best cytotoxicity was demonstrated by the fraction C2AM3P with a cell viability of 7.1 ± 0.2 % while AM1C had a viability of 20.2 ± 1.2 %. Several pure metabolites were isolated and four of these were positively identified as steroids. Of these steroids the structure of three novel metabolites from A. mannii was deduced. The study showed promising antibacterial, antifungal, anti – tuberculosis, antimalarial and anticancer activity of A. mannii. These results validate the use of A. manni against cancer, skin inflammation which is caused by fungus, malaria and bacterial diseases.
- Full Text:
- Date Issued: 2017
- Authors: Makoni, Pfungwa Gervase
- Date: 2017
- Subjects: Anonidium mannii -- Therapeutic use , Botanical chemistry , Annonaceae -- Therapeutic use , Apocynaceae -- Therapeutic use , Malaria -- Chemotherapy , Tuberculosis -- Chemotherapy , Bacterial diseases -- Chemotherapy , Cancer -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4797 , vital:20725
- Description: Anonidium mannii is a plant of the Annonaceae genus which is used traditionally in Africa for the treatment of gonorrhoea, malaria, cancer, skin inflammation and dysentery. In this study we will evaluate antimalarial, antifungal, anti - tuberculosis, antibacterial activities and cytotoxicity of different fractions in order to provide a scientific rationale for the traditional use of Anonidium mannii as well as provide possible novel drugs in the treatment of multi drug resistant strains of parasites and bacteria. Extracts from dried leaves were obtained by using solvent extraction and different fractions obtained using column chromatography eluted with solvents of varying polarities to obtain a wide range of metabolites. The antimalarial activity of the various fractions and some pure compounds was evaluated using plasmodium lactate dehydrogenase (pLDH) assay. Cytotoxicity was evaluated using HeLa cells while anti – tuberculosis assay was evaluated using the green fluorescent protein. Antibacterial activity of the extracts was evaluated using micro-dilution assay against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) bacteria and Gram-negative (Escherichia coli and Salmonella typhi) bacteria. Antifungal activity was evaluated against Candida albicans. The antimalarial assays yielded some fractions with promising IC50 values. The selected fractions yielded activities ranging between 0.73 μg/mL and 20.23 μg/mL. The fraction with the best activity was obtained from a hexane/ethyl acetate fraction. AM1C, a cholestane, showed the best activity from the pure metabolites that were screened. AM3C, stigmasterol, a pure compound gave the best antifungal activity with an MIC of 0.063 μg/mL. AM9C another pure compound (sterol) showed the best activity against S. typhi with a value of 0.031 μg/mL. AM2C a pure compound showed an activity of 0.063 μg/mL against E. faecalis. The best cytotoxicity was demonstrated by the fraction C2AM3P with a cell viability of 7.1 ± 0.2 % while AM1C had a viability of 20.2 ± 1.2 %. Several pure metabolites were isolated and four of these were positively identified as steroids. Of these steroids the structure of three novel metabolites from A. mannii was deduced. The study showed promising antibacterial, antifungal, anti – tuberculosis, antimalarial and anticancer activity of A. mannii. These results validate the use of A. manni against cancer, skin inflammation which is caused by fungus, malaria and bacterial diseases.
- Full Text:
- Date Issued: 2017
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