Antiproliferative Effect of 24‐Deoxysericoside From <scp> <i>Terminalia macroptera</i> </scp> Guill. &amp; Perr. (Combretaceae) Against Breast Carcinoma: In Vitro, Molecular Docking and <scp>ADME</scp> Assessment

Abstract

ABSTRACT Background Terminalia macroptera (Combretaceae) is an important medicinal plant in the traditional pharmacopeia in most tropical areas, where its different parts are used in treating illnesses including cancer. Aims In this study, two oleanane‐type triterpenoids: terminolic acid (TM32) and arjungenin (TM34), together with three saponins: arjunglucoside I (TM35), 24‐deoxysericoside (TM36) and chebuloside II (TM37) from T. macroptera , were screened for their cytotoxic effects against breast cancer cell lines. Methods and Results The compounds were isolated using column chromatography and characterized from their NMR data. Their cytotoxic and antiproliferative effects against estrogen non‐sensitive (MDA‐MB 231) and estrogen sensitive (MCF‐7) breast cancer cell lines were evaluated. Against estrogen non‐sensitive (MDA‐MB 231) cancer cell lines, deoxysericoside (TM36) was profoundly active compared to the control. Terminolic acid (TM32), arjungenin (TM34), and arjunglucoside I (TM35) were also active. Against estrogen sensitive (MCF‐7) breast cancer cell lines, deoxysericoside (TM36) exhibited significant activity ( p &lt; 0.05) compared to control experiments. The most active compound had an optimum concentration of 30 μg/mL. Deoxysericoside (TM36) showed concentration‐dependent inhibition percentages at 15 and 30 μg/mL, and MDA‐MB 231 breast carcinoma cells were more susceptible. MDA‐MB 231 treated with 15 and 30 μg/mL of deoxysericoside (TM36) showed significant reduction ( p &lt; 0.05) in clone formation after 48 h when compared to untreated controls, suggesting that it can restrict cancer to a preliminary stage. The deoxysericoside (TM36) reduced cell migration with dose‐dependent improvement in wound healing at 15 and 30 μg/mL, revealed by the micrographs. Molecular docking indicated that the compounds fit well into hERα and PI3Kα receptor binding sites, forming stable complexes with binding energies in ranges of −9.04 to −5.02 kcal mol −1 (hERα receptor) and −8.84 to −5.97 kcal mol −1 (PI3Kα receptor). The compounds exhibited appreciable drug likeness predicted using SwissADME. Conclusion The studies showed that the isolated compounds could be used for the development of anticancer therapies.