Antiplasmodial Activity of The Low Molecular Weight Compounds from Streptomyces sp. GMR22

Tarsa Ruli Tambunan; Jaka Widada; Ema Damayanti; Tutik Dwi Wahyuningsih; Mustofa Mustofa

doi:10.22146/ijp.634

Tarsa Ruli Tambunan Study Programfor Biotechnology, Graduate School, Universitas Gadjah Mada, Barek, Yogyakarta 55281, Indonesia
Jaka Widada Department of Agricultural Microbiology, Faculty of Agriculture, Universitas Gadjah Mada, Bulaksumur, Yogyakarta 55281, Indonesia
Ema Damayanti Study Programfor Biotechnology, Graduate School, Universitas Gadjah Mada, Barek, Yogyakarta 55281, Indonesia
Tutik Dwi Wahyuningsih Department of Chemistry, Universitas Gadjah Mada, Sekip Utara PO Box: BLS21, Yogyakarta 55281, Indonesia
Mustofa Mustofa Department ofPharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia

Keywords: low molecular weight compounds, Streptomyces, antiplasmodial, antimalarial

Abstract

Low molecular weight (LMW) antiplasmodial compounds isolated from bacteria, particularly Streptomyces have not been widely reported. This study aimed to identify LMW compounds from Streptomyces sp. GMR22 as antiplasmodial. Isolation of the LMW compounds from the supernatant of fermentation culture using solvent of n-hexane:ethylacetate (EtOAc) (85:15v/v)and identified using gas chromatography-mass spectrometry (GC-MS). Antiplasmodial assay of n-hexane:EtOAc extract was carried out in vitro against P. falciparum (3D7). Parasitemia percentage obtained through microscopic observations and 50% inhibitory concentration (IC₅₀) obtained through probit analysis. The antiplasmodial confirmation test was done by flow cytometry using SYBR Green I for Plasmodium DNA and anti-human CD235a for erythrocytes. The LMW compounds were investigated using SwissADME for drug-likeness. n-Hexane:EtOAc extract contained 21 LMW compounds from alcohol, hydrocarbon, ester, aromatic/diester, diester, fatty acid, and triester classes, which possessed moderate antiplasmodial activity with an IC₅₀ value of 38.61 ± 19.06 µg/mL. Confirmation by flow cytometry analysis showed that the extract at 50 µg/mL exhibited antiplasmodial activity based on a decreased Plasmodium DNA intensity as compared to the control group. The result of drug-likeness screening obtained that 3 LMW compounds were drug-likeness, namely phenylethyl alcohol, ethyl citrate, and di-n-butyl phthalate. Streptomyces sp. GMR22 produced LMW compounds as antiplasmodial, and further study was needed for identification of antiplasmodial active compounds.

Author Biography

Ema Damayanti, Study Programfor Biotechnology, Graduate School, Universitas Gadjah Mada, Barek, Yogyakarta 55281, Indonesia

ResearchDivisionfor Natural Product Technology, Indonesian Institute of Sciences, Jl. Jogja–Wonosari
Gunungkidul, Yogyakarta 55861, Indonesia

References

Alimuddin, A., Asmara, W., Widada, J., Mustofa, M., and Nurjasmi, R. (2010). An actinomycetes producing anticandida isolated from cajuput rhizosphere: partial identification of isolates and amplification of PKS-I genes. Indonesian Journal of Biotechnology, 15(1), 1-8.

Boyom, F. F., Ngouana, V., Kemgne, E. A. M., Zollo, P. H. A., Menut, C., Bessiere, J. M., Gut, J., and Rosenthal, P. J. (2011). Antiplasmodial volatile extracts from Cleistopholis patens Engler & Diels and Uvariastrum pierreanum Engl.(Engl. & Diels)(Annonaceae) growing in Cameroon. Parasitology research, 108(5), 1211-1217.

Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports, 7, 42717.

de Lima Procópio, R. E., da Silva, I. R., Martins, M. K., de Azevedo, J. L., and de Araújo, J. M. (2012). Antibiotics produced by Streptomyces. The Brazilian Journal of infectious diseases, 16(5), 466-471.

Dery, V., Duah, N. O., Ayanful-Torgby, R., Matrevi, S. A., Anto, F., and Quashie, N. B. (2015). An improved SYBR Green-1-based fluorescence method for the routine monitoring of Plasmodium falciparum resistance to anti-malarial drugs. Malaria Journal, 14(1), 1-6.

Durant, A. A., Rodríguez, C., Herrera, L., Almanza, A., Santana, A. I., Spadadora, C., and Gupta, M. P. (2014). Anti-malarial activity and HS-SPME-GC-MS chemical profiling of Plinia cerrocampanensis leaf essential oil. Malaria Journal, 13(1), 1-9.

Fitriastuti, D., Julianto, T. S., and Iman, A. W. N. (2020). Identification and Heme Polymerization Inhibition Activity (HPIA) Assay of Ethanolic Extract and Fraction of Temu Mangga (Curcuma mangga Val.) Rhizome. EKSAKTA: Journal of Sciences and Data Analysis, 20(1), 64-72.

Herdini, C., Mubarika, S., Hariwiyanto, B., Wijayanti, N., Hosoyama, A., Yamazoe, A., Nojiri, H., and Widada, J. (2017). Secondary bioactive metabolite gene clusters identification of anticandida-producing Streptomyces sp. GMR22 isolated from Wanagama forest as revealed by genome mining approach. Indonesian Journal of Pharmacy, 28(1), 26-33.

Isaka, M., Yangchum, A., Rachtawee, P., Komwijit, S., and Lutthisungneon, A. (2010). Hopane-type triterpenes and binaphthopyrones from the scale insect pathogenic fungus Aschersonia paraphysata BCC 11964. Journal of natural products, 73(4), 688-692.

Jenett‐Siems, K., Mockenhaupt, F. P., Bienzle, U., Gupta, M. P., and Eich, E. (1999). In vitro antiplasmodial activity of Central American medicinal plants. Tropical Medicine & International Health, 4(9), 611-615.

Jiang, Z., Kempinski, C., and Chappell, J. (2016). Extraction and analysis of terpenes/terpenoids. Current protocols in plant biology, 1(2), 345-358.

Kaharudin, F. A., Zohdi, R. M., Mukhtar, S. M., Sidek, H. M., Bihud, N. V., Rasol, N. E., Ahmad, F. B., and Ismail, N. H. (2020). In vitro antiplasmodial and cytotoxicity activities of crude extracts and major compounds from Goniothalamus lanceolatus. Journal of ethnopharmacology, 254, 112657.

Kotepui, M., Piwkham, D., PhunPhuech, B., Phiwklam, N., Chupeerach, C., and Duangmano, S. (2015). Effects of malaria parasite density on blood cell parameters. PLoS One, 10(3), e0121057.

Lambros, C., and Vanderberg, J. P. (1979). Synchronization of Plasmodium falciparum erythrocytic stages in culture. The Journal of parasitology, 418-420.

Lipinski, C. A. (2004). Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337-341.

Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46(1-3), 3-26.

Mota, M. L., Lobo, L. T. C., da Costa, J. M. G., Costa, L. S., Rocha, H. A., e Silva, L. F. R., Pohlit, A. M., and de Andrade Neto, V. F. (2012). In vitro and in vivo antimalarial activity of essential oils and chemical components from three medicinal plants found in northeastern Brazil. Planta medica, 78(07), 658-664.

Mustofa, Sholikhah, E., and Wahyuono, S. (2007). In vitro and in vivo antiplasmodial activity and cytotoxicity of extracts of Phyllanthus niruri L. herbs traditionally used to treat malaria in Indonesia. Southeast Asian J Trop Med Public Health, 38(4), 609-615.

Nurjasmi, R., Widada, J., and Ngadiman, N. (2009). Diversity of actinomycetes at several forest types in Wanagama I Yogyakarta and their potency as a producer of antifungal compound. Indonesian Journal of Biotechnology, 14(2), 1196-1205.

Roy, R. N., Laskar, S., and Sen, S. K. (2006). Dibutyl phthalate, the bioactive compound produced by Streptomyces albidoflavus 321.2. Microbiological research, 161(2), 121-126.

Schmidt, R., Cordovez, V., De Boer, W., Raaijmakers, J., and Garbeva, P. (2015). Volatile affairs in microbial interactions. The ISME journal, 9(11), 2329-2335.

Sukmawati, N. (2018). Potency of volatile organic compounds from Streptomyces sp. GMR22 and GMY01 in inhibiting Fusarium oxysporum f.sp. cubense (Foc). growth. Undergraduate Thesis, Universitas Gadjah Mada, Indonesia.

Trager, W., and Jenson, J. B. (1978). Cultivation of malarial parasites. Nature, 273(5664), 621-622.

Tyc, O., Song, C., Dickschat, J. S., Vos, M., and Garbeva, P. (2017). The ecological role of volatile and soluble secondary metabolites produced by soil bacteria. Trends in microbiology, 25(4), 280-292.

Wu, Y., Yuan, J., E, Y., Raza, W., Shen, Q., and Huang, Q. (2015). Effects of volatile organic compounds from Streptomyces albulus NJZJSA2 on growth of two fungal pathogens. Journal of basic microbiology, 55(9), 1104-1117.

Xing, M., Zheng, L., Deng, Y., Xu, D., Xi, P., Li, M., Kong, G., and Jiang, Z. (2018). Antifungal activity of natural volatile organic compounds against litchi downy blight pathogen Peronophythora litchii. Molecules, 23(2), 358.

Yamada, Y., Kuzuyama, T., Komatsu, M., Shin-ya, K., Omura, S., Cane, D. E., and Ikeda, H. (2015). Terpene synthases are widely distributed in bacteria. Proceedings of the National Academy of Sciences, 112(3), 857-862.