Synthesis and In-Vitro Evaluation of Raloxifene–Oxalyl Chloride Conjugate Targeting Breast Cancer

Anticancer drugs mostly produce minimal to severe side effects due to lack of selectivity. The present work envisaged selective targeting of MCF-7 breast cancer cells by synthesizing an ester conjugate using oxalyl chloride of drug raloxifene targeted for steroidal estrogen receptor alpha. The objective was to synthesize and evaluate raloxifene–oxalyl chloride conjugate as anticancer drug with side effects reduced by increasing selectivity. Synthesis of the conjugate was carried out by reflux condensation of acid chloride of oxalyl chloride with raloxifene. In vitro methods viz. lipophilicity, solubility, protein binding, drug release and permeation, hydrolysis, and cytotoxicity were employed for characterization and evaluation of the drug conjugate. The solubility and partition coefficient studies had an outcome of better solubility and lipophilicity while protein binding studies revealed a low protein binding capacity of the drug conjugate. The hemolytic study showed lesser RBC lysis with significant cytotoxicity compared to the parent drug and a selective diffusion at the pH of cancer cells rather than pH of normal cells, and hence increasing the specificity and minimizing the adverse effects. Hydrolytic study of the conjugate signified minimal hydrolysis of the conjugate at various pH, simulated gastric fluid, and simulated intestinal fluid. The synthesized conjugate thus ratifies to be a useful prodrug in reducing the systemic toxicity of raloxifene as well as selectively targeting the cancerous cells.