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Article

Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study

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Drug Discovery Research Group, Faculty of Pharmacy, Sanata Dharma University, Campus III, Paingan, Maguwoharjo, Sleman 55282, Indonesia
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Pharmacy Program, Faculty of Science and Technology, Ma Chung University, Malang 65151, Indonesia
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Faculty of Pharmacy, Padjadjaran University, Jatinangor, Sumedang 45363, Indonesia
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Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institute of Biotechnology Malaysia, Halaman Bukit Gambir, Bayan Lepas 11900, Malaysia
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Pharmaceutical Technology Department, School of Pharmaceutical Sciences and USM-RIKEN Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Minden 11800, Malaysia
*
Author to whom correspondence should be addressed.
Academic Editor: Elisa Nuti
Molecules 2020, 25(20), 4691; https://doi.org/10.3390/molecules25204691
Received: 18 September 2020 / Revised: 11 October 2020 / Accepted: 12 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue Metalloenzyme Inhibitors and Activators II)
Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a step-by-step in vitro screening against MMP9 was performed from its crude extract, partitions until fractions using FRET-based assay. The partitions were obtained by performing liquid–liquid extraction on the methanol extract using n-hexane, ethylacetate, n-butanol, and water representing nonpolar to polar solvents. The fractions were made from the selected partition, which demonstrated the best inhibition percentage toward MMP9, using column chromatography. Of the 200 compounds screened, 20 compounds that scored the binding affinity −11.2 to −8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. Six of the eight crude extracts demonstrated inhibition toward MMP9 with the IC50 24 to 823 µg/mL. The partitions (1 mg/mL) of Ageratum conyzoides aerial parts and Ixora coccinea leaves showed inhibition 94% and 96%, whereas their fractions showed IC50 43 and 116 µg/mL, respectively toward MMP9. Using MTT assay, the crude extract of Ageratum exhibited IC50 22 and 229 µg/mL against 4T1 and T47D cell proliferations, respectively with a high safety index concluding its potential anti-breast cancer from herbal. View Full-Text
Keywords: MMP9; PEX9; cancer; bioguided; fractionation; ageratum; screening; in silico; in vitro MMP9; PEX9; cancer; bioguided; fractionation; ageratum; screening; in silico; in vitro
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MDPI and ACS Style

Hariono, M.; Rollando, R.; Karamoy, J.; Hariyono, P.; Atmono, M.; Djohan, M.; Wiwy, W.; Nuwarda, R.; Kurniawan, C.; Salin, N.; Wahab, H. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study. Molecules 2020, 25, 4691. https://doi.org/10.3390/molecules25204691

AMA Style

Hariono M, Rollando R, Karamoy J, Hariyono P, Atmono M, Djohan M, Wiwy W, Nuwarda R, Kurniawan C, Salin N, Wahab H. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study. Molecules. 2020; 25(20):4691. https://doi.org/10.3390/molecules25204691

Chicago/Turabian Style

Hariono, Maywan, Rollando Rollando, Jasson Karamoy, Pandu Hariyono, M. Atmono, Maria Djohan, Wiwy Wiwy, Rina Nuwarda, Christopher Kurniawan, Nurul Salin, and Habibah Wahab. 2020. "Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study" Molecules 25, no. 20: 4691. https://doi.org/10.3390/molecules25204691

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