Tetralone derivatives have previously proven their potential activity as anticancer candidates. The potential anticancer activity of a series of tetralone compounds 3–14 with a sulfonamide scaffold was synthesized and investigated.. The invitro anticancer evaluation in the present study was done on a seven different human cancerous cells. Following studying the safety of all the synthesized compounds on normal human cells, IC50 values were identified for promising compound 11. Our findings showed that compound 11 selectively has anti-breast potentiality (MCF-7). Upon studying the molecular effect of compound 11 on different apoptotic proteins like BCL2, Bax, and caspase-7, compound 11 signaled an apoptotic cascade in breast cancer cells, producing cell cycle arrest at the G2/M phase. Investigation of the binding interaction, dynamic nature, and protein-ligand stability was carried out using molecular dynamics (MD) simulation. MD simulation analytical characteristics (RMSD, RMSF, and RoG) indicated that compound 11 was stable during the 20 ns MD simulation investigation. Meanwhile, MD simulation showed that compound 11 selectively targeted the catalytic-binding pocket residues, with the naphthalene group interacting into the small hydrophobic pocket provided by Asn 94, Arg 133, Tyr 137, Ile 139, Ala 148, Tyr 149, Cys 196, Val 197, and Val 198 in caspase-7, and by the residues Tyr 46, Ala 49, Phe 50, Leu 53, Val 71, Leu 75, Arg 84, Ala 87 and Ser 90 in BCL2 receptor. The absorption, metabolism, and carcinogenic properties of compound 11 ADMET predictions were carried out. Based on our physicochemical, docking, dynamics simulation, and ADMET prediction results, compound 11 is considered as a new effective and selective anticancer candidate.