Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach

Ahmad, Siti Junaidah; Rahim, Mohd Badrin Hanizam Abdul; Baharum, Syarul Nataqain; Baba, Mohd Shukri; Zin, Noraziah Mohamad

doi:10.1155/2017/2189814

Cited by 8 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Streptomyces is the largest genus of the Actinobacteria phylum and the most important for the pharmaceutical industry [8]. Members of this group of Gram positive bacteria are well known for their outstanding capacity to produce active secondary metabolites, including antibiotic, antitumor, antimalarial and immunosuppressive agents [9][10][11][12][13]. Such variety of biological properties is due to the large diversity of structurally distinct compounds produced by over 900 species of Streptomyces [14].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

et al. 2020

View full text Add to dashboard Cite

Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The antimalarial compound gancidin was isolated from Streptomyces sp 7 . At doses of 6.25 and 3.125 μg/kg, it can inhibit nearly 80% of malarial parasites.…”

Section: Discussionmentioning

confidence: 99%

“…Animals and microbes have also been assessed 6 . Streptomyces is one of many microbial genera that has long been known for its anti-parasitic and anti-pathogenic metabolites, including antimalarials 7 .…”

Section: Introductionmentioning

confidence: 99%

In vitro Test for Inhibition of Plasmodium falciparum 3D7 Parasites using Streptomyces hygroscopicus subsp. hygroscopicus Strain i18, Isolated from a Pineapple Farm in Lampung

Setyaningrum¹,

Nukmal²,

Aeny³

et al. 2021

J Pure Appl Microbiol

View full text Add to dashboard Cite

Increasing natural ingredient awareness and utilization has created an increased demand for sources of natural medicinal ingredients, including sources of compound used to treat malaria. Streptomyces is a genus of prokaryote well recognized for its production of antibiotics and other pharmaceutically useful compound. This study aimed to assess the ability of unpurified fermentation metabolites to inhibit Plasmodium parasites. A strain of bacteria identified as Streptomyces hygroscopicus subsp. hygroscopicus strain i18 were isolated from pineapple fields in Lampung province, and was cultured and fermented on liquid synthetic Gause medium for 10 days. The supernatant was separated from the cells and extracted with ethyl acetate-methanol (1:1). Plasmodium falciparum 3D7 was used for antiplasmodial testing. Metabolites were tested qualitatively using a phytochemical approach. Saponins and triterpenoids were found to be present in the extract. Parasite inhibition as measured using probit analysis and yielded an IC50 value of 11.07 g.m/L. These findings suggest further examinations of this extract (e.g. assessment of off-target effects) are warranted.

show abstract

“…4 There are differences in the inhibitory activity due to the types of organic solvent used for the extraction. 27 Based on the IC 50 results and comparisons of the IC 50 value parameters, it could be inferred that the secondary metabolite compound of Streptomyces sp has the best inhibitory power. The mechanism of secondary metabolite of Streptomyces sp to inhibit the growth of Plasmodium falciparum is related to presence of chemical compounds that are active as inhibitors of proteases in Trypsin, Chymotrypsin and Proteinase K. 28 Proteases are needed by Plasmodium stage merozoites to breakdown and invase subsequent erythrocytes and to decrease hemoglobin by trophozoitin K. intraerythrocytic.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of secondary metabolite extract of Streptomyces sp. on Plasmodium falciparum in vitro: A study of soil sediment of Papua's Hamadi mangrove forest

Sandy

Sasto²

2020

JKKI

View full text Add to dashboard Cite

Background: Reports about the resistance of antimalarial drugs demand exploration and development of new drugs. Indonesia's vast maritime area and abundance of mangrove forests have the potential for the development and discovery of active anti-cancer substances, antibiotics and antiplasmodial. Studies on the potential of new drugs from this sector are still limited. Objective: The purpose of this study was to see the potential of Actinomycetes genus Streptomyces sp. as an antiplasmodial in the Hamadi Coast of Papua. Methods: Retrieval of mangrove soil sediments to isolate Streptomyces was located in the Hamadi-Jayapura mangrove forest. Selective isolation was conducted by SCA (Starch Casein Agar) selective media. Identification of Streptomyces sp was examined microscopically through observation of colony morphology and gram staining. The results of isolation of Streptomyces were then fermented on FM3 media until finally secondary metabolite extract of Streptomyces was obtained. The secondary metabolite extract of Streptomyces was tested for its inhibition on the development of Plasmodium falciparum. Result: Analysis of inhibition of the secondary metabolite extract of Streptomyces sp on the development of Plasmodium falciparum showed good results because the extract of Streptomyces sp with a concentration of 100 µg/mL could suppress average growth values of Plasmodium falciparum to only 0.66% with an average inhibitory value of 95.20%. This value followed levels of extract concentration by the lowest concentration of 0.01 µg/mL, the average value of Plasmodium falciparum growth which increased to 10.89% with an average inhibition value of 20.83%. IC 50 analysis of Plasmodium falciparum in culture for 48 hours was 0.12 µg/ mL, and this value was very good because a test of substance has very good inhibitory activity when the IC 50 value is ≤ 10 μg/mL. Conclusion: Streptomyces' secondary metabolite extract from mangrove sediments showed a very good ability to inhibit the growth of Plasmodium falciparum so that it could have potential as a source of antiplasmodial. Latar Belakang: Laporan adanya resistensi obat-obatan antimalaria menuntut eksplorasi dan pengembangan obat baru. Kawasan maratim Indonesia yang luas dan kelimpahan habitat hutan mangrove berpotensi untuk pengembangan dan penemuan zat aktif anti kanker, antibiotik, antiplasmodium. Informasi dan penelitian potensi obat baru dari sektor ini masih sangat terbatas dilakukan penelitian.

show abstract

Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach

Cited by 8 publications

References 56 publications

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

In vitro Test for Inhibition of Plasmodium falciparum 3D7 Parasites using Streptomyces hygroscopicus subsp. hygroscopicus Strain i18, Isolated from a Pineapple Farm in Lampung

Inhibition of secondary metabolite extract of Streptomyces sp. on Plasmodium falciparum in vitro: A study of soil sediment of Papua's Hamadi mangrove forest

Contact Info

Product

Resources

About