在我们的研究中，通过缩合4-羟基苯胺酰苯胺（3a-c）和5-氯甲基-3-芳基-1,2,4-噁二唑（6a-d），我们设计和合成了一系列新颖的4-氨基苯胺酰-1,2,4-噁二唑杂环类似物。通过各种光谱技术（1H NMR，13C NMR，IR和LC-MS）验证了合成化合物的结构。所制备的所有化合物都经过了体外和体内的抗增殖研究，对TNBC细胞系MDA-MB-468和MDA-MB-231进行了测试。研究发现，化合物7k显著促进了MDA-MB-468和MDA-MB-231细胞的凋亡，其IC50值分别为22.31 µM和26.27 µM。化合物7k与MAPK的关键活性位点发生相互作用，并展现出最高的-7.06 kcal/mol的对接得分。对接结果通过模拟100 ns的分子动力学研究进行验证，揭示了与MAPK的各种稳定相互作用。因此，化合物7k与氨基酸残基进行了稳定的氢键和π-π堆积，并形成了π-cation相互作用。我们的研究表明，化合物7k的体外抗增殖研究与体内模拟研究具有良好的相关性。因此，7k被视为通过下调MAPK P38抑制TNBC的潜在新型前体。Ramaswamy H. Sarma通讯。

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 (3a-c) and 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (6a-d). The structure of the synthesised compounds was verified by various spectroscopic techniques (1H NMR, 13C NMR, IR and LC-MS). All the prepared compounds were subjected to in silico and in vitro antiproliferative study against TNBC cell lines MDA-MB-468 and MDA-MB-231. The investigations revealed that compound 7k significantly promoted apoptosis against MDA-MB-468 and MDA-MB-231 cells with IC50 values of 22.31 µM and 26.27 µM, respectively. Compound 7k 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, 7k forms stable H-Bonds and π-π stacking with amino acid residues along with π-cation. Our investigations reveal that the in vitro antiproliferative study of 7k was in good correlation with the in silico studies. Hence, 7k serves as a potential novel lead for the inhibition of TNBCs by downregulating MAPK P38.Communicated by Ramaswamy H. Sarma.