R2- C(S)- NH- N =CH- R1 [R1 = o-OCH2CH3 & R2 = C4H9N (2-EBP), R1 = o-OCH2CH3 & R2 = C4H9NO (2EBM), R1 = p-OCH2CH3 & R2 = C4H9N (4-EBP), and R1 = p-OCH2CH3 & R2 = C4H9NO (4-EBM)] have been synthesized. The ligands have been verified via various spectroscopic methods such as IR, NMR, etc. Single- crystal X-ray diffraction methods were applied to identify the structure of 4-EBP. Absorption/emission spectroscopic titration was used to assess the interaction of ligands to calf thymus (CT) DNA. DNA binding studies revealed interactions characterized by hyperchromicity and a slight redshift. 4-EBP showed the highest binding constant (1.58 x 105), indicating that it binds stronger to CT-DNA. The red shift and significant hypochromic shift seen in the fluorescence titration spectra of the BSA binding probes showed the strong interaction of the ligand to BSA. EGFR protein docking investigations verified the potential of the ligands to treat its targets. 4-EBP has the highest docking score (-6.7987 kcal) compared to other synthesized ligands. The B3LYP/6-311 G (d, p) ++ was implemented to calculate density functional theory (DFT). All ligands have a LogP value below 5, indicating lipophilic properties suitable for SwissADME studies. All new ligands follow Lipinski's drug class rules. Low synthetic input levels between 2 and 3 indicate the best results for this material. Each ligand (2-EBP to 4EBM) has been marked to perform as an oral drug candidate. To test the anticancer potential of four ligands (2EBP to 4-EBM). 4-EBP showed good efficacy against endothelial and liver cancer cells, with IC50 values of 21.2 +/- 0.1 and 45.3 +/- 0.1 against MCF-7 and HepG-2 respectively. C1 [Singh, Vipin; Sreekanth, Anandaram] Natl Inst Technol Tiruchirappalli, Dept Chem, Tiruchirappalli 620015, Tamil Nadu, India. [Haribabu, Jebiti] Univ Atacama, Fac Med, Carreras 1579, Copiapo 1532502, Chile. [Arulraj, Arunachalam] Univ Tecnol Metropolitana UTEM, Fac Ingn, Dept Elect, Av Jose Pedro Alessandri 1242, Santiago 7800002, Chile. [Vediyappan, Ramesh] Madurai Kamaraj Univ, Sch Chem, Dept Organ Chem, Madurai 625021, Tamil Nadu, India. C3 National Institute of Technology (NIT System); National Institute of Technology Tiruchirappalli; Universidad de Atacama; Universidad Tecnologica Metropolitana; Madurai Kamaraj University