Abstract 5743: Design and synthesis of novel strifluoromethyl-thiazolidine analogs as anticancer agents

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. This underscores the urgent need for novel therapeutic approaches that offer greater efficacy and safety. Targeted therapies using small molecules are a promising strategy due to their ability to selectively inhibit cancer cells, minimizing damage to normal tissues. A library of derivatives (N3-N6 and V1-V8) containing the trifluoromethyl phenyl acetamide core was synthesized 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 trifluoromethyl phenyl acetamide scaffold is of particular interest in medicinal chemistry due to its favorable pharmacological properties, including enhanced stability, lipophilicity, and metabolic resistance. Our study aimed to synthesize and evaluate derivatives of trifluoromethyl phenyl acetamide for their cytotoxic potential against various cell lines, such as colorectal cancer (HT-29, MC38, CT26and COLO 205), hepatic (C3a and PLC/PRF), pancreatic (Suit-2, MiaPaca2, As-PC1 and Panc 02.03, CI66), 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 breast epithelial cell line MCF10a was included to evaluate the toxicity of lead compounds. Based on the SRB assay the 12 compounds exhibited variable but significant cytotoxic effects in various cancer cell lines. Further experiments are in progress to validate the most effective compounds in selected cancer models. Citation Format: Mohamed A. Eltokhy, Eman A. Fayed, Moustafa S. Abusaif, Ahmed Rageb, Aya Thabet, Yousry A. Ammar, Sanjay K. Srivastava. Design and synthesis of novel strifluoromethyl-thiazolidine analogs as anticancer agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5743.