Abstract
This study delves into the exploration of Clindamycin derivatives, specifically compounds 3 and 3e, to unveil their antitumor potential by employing a multidisciplinary approach. Screening a repertoire of 200 Clindamycin-associated targets pinpointed the Family A G-protein-coupled receptor as a prominent antitumor candidate. Subsequent analyses unearthed 16 pertinent antitumor proteins, with compound 3 exhibiting robust affinity towards a specific protein via stable hydrogen bonding. Molecular dynamics simulations underscored the adrenergic receptor β as a pivotal target, primarily situated in the plasma membrane and endoplasmic reticulum. These revelations hint towards compound 3's potential to bolster natural defense mechanisms against tumors by modulating immune responses within the tumor microenvironment, thus paving the way for novel avenues in antitumor drug development. Furthermore, employing the MTT assay, we evaluated the anti-HepG2 cell activity of compounds 3 and 3e, with 5-fluorouracil serving as the control drug. Results revealed that compound 3 exhibited significant differences (p < 0.01) across all concentrations (2.5, 5, 10 μg/mL) compared to the control group, paralleled by the pronounced differences (p < 0.01) observed with 5-fluorouracil.