Electronic, Structural and Molecular Implications of Curcumin and Its Relationship with Apoptosis in A549 Cells

This study investigates the electronic and molecular structure of curcumin through computational analysis, employing density functional theory (DFT) to determine its global reactivity descriptors (GRDs). Furthermore, the energy gap was determined by characterizing the HOMO-LUMO frontier molecular orbitals. The resulting electronic fingerprint indicates a highly reactive molecule with a remarkable capacity to donate electrons, giving it an electrophilic character. Curcumin is used in traditional Eastern medicine as an anti-inflammatory, antioxidant, and anticancer agent; it is a natural polyphenol derived from Curcuma longa. Recent studies have reported that curcumin exhibits significant antitumor activity against non-small cell lung cancer in the A549 cell line model. The global reactivity descriptors (GRDs) obtained in this study were found to correlate with findings from previous in vitro and in vivo experiments, supporting curcumin’s capacity to induce programmed cell death through multiple signaling pathways, including oxidative stress-mediated apoptosis, ferroptosis, and the activation of autophagy. The study further demonstrates a correlation between the observed synergistic effects of curcumin and conventional chemotherapeutic agents. Finally, these results offer a theoretical framework for understanding the relationship between global reactivity descriptors (GRDs) and the biological mechanisms of curcumin at the quantum level, supporting its potential as a complementary therapeutic agent in the treatment of lung cancer.