Discovery of New 7-Propanamide Benzoxaborole as Potent Anti-SKOV3 Agent via 3D-QSAR Models

Benzoxaboroles have garnered significant interest for their therapeutic potential in various diseases. Among them, 7-propanamide benzoxaborole has served as a new and valuable chemotype for anti-cancer agents, although their definitive intracellular target(s) remains elusive. Herein, three-dimensional quantitative structure-activity relationship (3D-QSAR) was used to systematically investigate the structure-activity relationships (SAR) of a series of 7-propanamide benzoxaboroles. Comparative molecular field analysis (CoMFA, r² = 0.991, q² = 0.626) and comparative molecular similarity indices analysis (CoMSIA, r² = 0.964, q² = 0.605) revealed critical structural determinants of 7-propanamide benzoxaboroles for inhibition of the ovarian cancer cell (SKOV3) proliferation. Based on the guidance of the critical structural determinants, we designed a new benzoxaborole compound <b>42</b> with high predicted inhibition activity values. In vitro proliferation assessment showed that compound <b>42</b> exhibited superior inhibitory potency to lead compound <b>1</b> and comparable activity to compound <b>41</b>. These findings indicated that the SAR of benzoxaborole compounds through 3D-QSAR can offer valuable theoretical insights for the structural optimization of new benzoxaboroles as anti-SKOV3 agents.