Spectroscopic, Quantum Chemical, Molecular Docking and In Vitro Cytotoxicity Studies on 1-(Chloromethyl)anthraquinone: A potent Lung Cancer Drug

Abstract

In this work, a comprehensive investigation of 1-(Chloromethyl)anthraquinone (CMAQ) was carried out using a combination of spectroscopic, quantum chemical, molecular docking, and in vitro cytotoxicity approaches to evaluate its potential as an anticancer candidate. The molecular structure was optimized using Density Functional Theory (DFT) at the B3LYP/cc-pVTZ level, confirming a stable C₁ point group geometry with a HOMO–LUMO energy gap of 4.18 eV, indicative of moderate chemical reactivity and stability. Frontier molecular orbital analysis, global reactivity descriptors, Mulliken charge distribution, and Molecular Electrostatic Potential mapping revealed electron-rich carbonyl oxygen atoms as favorable electrophilic sites and a chloromethyl substituent susceptible to nucleophilic substitution. Vibrational assignments from FT-IR and FT-Raman spectra were consistent with theoretical predictions, validating the computational model. Time-dependent DFT simulations showed excellent agreement with experimental UV–Vis absorption, confirming n → π* transitions characteristic of anthraquinone derivatives. Molecular docking studies demonstrated stronger binding affinity of CMAQ toward DPP-4 (−7.42 kcal/mol) compared with p38α MAPK (−6.21 kcal/mol). In vitro cytotoxicity assays revealed potent activity of CMAQ against A549 lung cancer cells (IC₅₀ = 4.12 μg/mL) and moderate activity against HeLa cervical cancer cells (IC₅₀ = 13.25 μg/mL), with apoptosis-like morphological changes confirmed microscopically. Overall, the integrated findings highlight CMAQ as a promising lead compound with preferential efficacy against lung cancer, supported by both computational and experimental evidence.