In Silico Exploration of Dietary Polyphenol, Bisdemethoxycurcumin as a Potential CXCL12 Inhibitor in Breast Cancer Treatment

Abstract

Breast cancer stands as one of the most prevalent malignancies in women worldwide. The World Health Organization reported 2.3 million new cases and 685,000 fatalities due to breast cancer in 2020. In India alone, 162,468 new diagnoses and 87,090 deaths were recorded in 2018. CXCL12, also known as stromal cell-derived factor 1 (SDF-1), plays a significant role in tumor progression and metastasis in breast cancer, rendering it a promising target for intervention. Curcumin and its derivatives are known to inhibit breast cancer and enhance the efficacy of chemotherapeutic drugs. This study explores the potential of Bisdemethoxycurcumin, a synthesized derivative of curcumin, as a CXCL12 inhibitor in breast cancer. Our in-silico screening of Bisdemethoxycurcumin demonstrated a strong binding affinity to CXCL12, surpassing that of the reference compound, Plerixafor. We also compared our lead molecule with the reference compound (Plerixafor). Conversely, we observe that Bisdemethoxycurcumin shows a good binding affinity with the target protein and shows a strong bond interaction, particularly H-bond interaction in molecular docking and MD simulation studies both. Our findings identify Bisdemethoxycurcumin as a lead compound for future studies, necessitating validation through in vitro and in vivo investigations.