| Summary: | In our previous work, the partitions (1 mg/mL) of <i>Ageratum conyzoides</i> (AC) aerial parts and <i>Ixora coccinea</i> (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC<sub>50</sub> 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC<sub>50</sub> determinations for AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC <i>n</i>-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC<sub>50</sub> as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10<sup>−2</sup> µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC <i>n</i>-hexane demonstrated IC<sub>50</sub> 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC<sub>50</sub> 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC<sub>50</sub> 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC<sub>50</sub> 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.
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