Rangappa S. Keri

Discovery of Novel Oxadiazole‐Triazole Hybrids as Lung and Cervical Cancer Agents: Synthesis, Docking, Biological Evaluation, and SAR Studies

ABSTRACT The number of new cancer cases and cancer‐related fatalities continues to rise nowadays as a result of better lives and higher survival rates. Recent research has primarily focused on developing multi‐target drug designs. A new series of fluorinated 1,3,4‐oxadiazole‐1,2,3‐triazole hybrids was designed and synthesized with high yield utilizing the substructure approach. The newly synthesized compounds were characterized using spectral analyses, including NMR ( 1 H, 13 C, and 19 F), mass spectrometry (MS), and high‐performance liquid chromatography (HPLC). Additionally, their in vitro anti‐cancer activity was evaluated against lung cancer A549 and cervical cancer HeLa cell lines. The results indicated that a number of the synthesized hybrids showed encouraging cytotoxic effects, significantly reducing cell proliferation in comparison to the control groups. Compounds ( 7c ), ( 9a ), and ( 9b ) exhibited high cytotoxicity against lung cancer cell lines, with IC 50 values of 19.47 to 21.65 μg/mL. Compound ( 7c ) exhibited significant activity against lung cancer, with an IC 50 value of 19.47 μg/mL. Compounds ( 7c ), ( 9a ), and ( 9b ) exhibited broad cytotoxic effects against the HeLa cell line, with IC 50 values of 17.07 μg/mL for ( 7c ), 19.21 μg/mL for ( 9a ), and 20.85 μg/mL for ( 9b ). Compound ( 7b ) outperformed the other compounds in anticancer activity against the cervical carcinoma HeLa cell line. In silico drug‐like properties indicated that they could be promising molecular frameworks for further studies. The binding modes of compounds ( 9a ) and ( 9b ) were analyzed, revealing the most favorable poses of these compounds within the active site of the tested EGFR (PDB ID: 8SC7) through a molecular docking study. Molecular dynamics simulations of compounds ( 9a ) and ( 9b ) highlighted the key amino acids in the enzyme's active region and provided insight into the mechanism of enzyme interactions.