Design, synthesis and docking studies of novel 4-aminophenol-1,2,4-oxadiazole hybrids as apoptosis inducers against triple negative breast cancer cells targeting MAP kinase.

In our study, a series of novel 4-aminophenol benzamide-1,2,4-oxadiazole hybrid analogues have been designed and synthesized by condensing 4-hydroxyphenyl arylamides and 5-chloromethyl-3-aryl-1,2,4-oxadiazoles The structure of the synthesised compounds was verified by various spectroscopic techniques (H NMR, C NMR, IR and LC-MS). All the prepared compounds were subjected to and antiproliferative study against TNBC cell lines MDA-MB-468 and MDA-MB-231. The investigations revealed that compound significantly promoted apoptosis against MDA-MB-468 and MDA-MB-231 cells with IC values of 22.31 µM and 26.27 µM, respectively. Compound interacted with crucial active sites of MAPK and exhibited the highest docking score of -7.06 kcal/mol. Docking was validated with molecular dynamic studies with simulation for 100 ns, depicting various stable interactions with MAPK. Consequently, forms stable H-Bonds and π-π stacking with amino acid residues along with π-cation. Our investigations reveal that the antiproliferative study of was in good correlation with the studies. Hence, serves as a potential novel lead for the inhibition of TNBCs by downregulating MAPK P38.Communicated by Ramaswamy H. Sarma.