Theoretical, In Vitro Antiproliferative, and In Silico Molecular Docking and Pharmacokinetics Studies of...

This study explores the design, synthesis, characterization, and pharmacological evaluation of chalcone-derived C-Mannich base compounds, which exhibit significant pharmacological potential in medicinal chemistry. A series of compounds 6(a-j) was designed and investigated for the physicochemical properties, drug-likeness, toxicity profile, and molecular interactions through in silico methods. Computational tools, including SwissADME online server and ProTox II web tool were utilized to assess their pharmacokinetics, druggability, and toxicity, while molecular docking investigations were performed with the ADT tools, AutoDock 4.2 software to ascertain the binding interactions of query molecules with critical protein targets, such as ESR1, ERBB2, PIK3CA, PIK3R1, EGFR, SRC, STAT3 and IGF1R. The selected compounds 6(a, c, e, i, and j) were synthesized via a modified Mannich reaction utilizing dehydrozingerone (DHZ) along with 3-hydroxy benzaldehyde and various secondary amines. The synthesized derivatives were characterized using the spectral and CHN elemental analysis. The in vitro antiproliferative potential of selected derivatives 6(a, c, e, i, and j) was evaluated against the MCF-7 (breast adenocarcinoma), A549 (Small cell lung carcinoma), HeLa (Cervical cancer), HeP2 (Colon cancer), HepG2 (Liver carcinoma) and NHDF (Normal Human Dermal Fibroplasts) the MTT assay using doxorubicin as standard. The study demonstrates that DHZ-derived C-Mannich base compounds possess significant anticancer efficacy, positioning them as promising candidates for subsequent therapeutic development.