Abstract Cancer is a global health crisis, ranking as one of the leading causes of mortality worldwide. Its persistent increase in incidence is driven by the intricate nature of tumor biology, rapid mutations, drug resistance, and limited efficacy of many current treatment options. These challenges highlight the need for mechanistically defined small-molecule therapeutics that selectively target tumor vulnerabilities while sparing normal tissues. Fluorinated scaffolds are of translational interest due to their ability to enhance metabolic stability, bioavailability, and drug-like properties. In this study, we synthesized and characterized a focused library of s-trifluoromethyl phenyl acetamide derivatives (N3-N6 and V1-V8) via a series of chemical reactions. The structural integrity of these compounds was verified through a combination of analytical techniques, including melting point determination, Proton Nuclear Magnetic Resonance (1H NMR), Carbon-13 Nuclear Magnetic Resonance (13C NMR), and Infrared (IR) spectroscopy. The s-trifluoromethyl phenyl acetamide scaffold is of particular interest in medicinal chemistry due to its favorable pharmacological properties, including enhanced stability, lipophilicity, and metabolic resistance. These compounds were evaluated for anticancer activity across a broad panel of human and murine cancer models, including colorectal cancer (HT-29, MC38, CT26and COLO 205), hepatic (C3a and PLC/PRF5), pancreatic (Suit-2, MiaPaca2, As-PC1 and Panc 02. 03), breast (MDA-MB-468, MDA-MB-231, BT20, MCF7, 4T1, 4T1 paclitaxel resistant, JIMT-1, ZR-75-1, E0771, T47D, and HCC1806) and ovarian (OVCAR-5) cell lines. Normal mammary epithelial cells (MCF10A) were included to assess therapeutic selectivity Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr LB031.
Eltokhy et al. (Fri,) studied this question.