一系列苯并噁唑基哌啶衍生物的小说系列计划，合成，并针对两种乳腺癌细胞系进行筛选。筛选化合物具有相当的抗增殖活性（对MCF-7和MDA-MB-231细胞系的IC50分别为33.32±0.2µM至7.31±0.43µM和1.66±0.08µM至12.10±0.57µM），比多柔比星更有效（分别为IC50=8.20±0.39µM和13.34±0.63µM）。活性化合物经过酶抑制活性测定，其中4d和7h表现出强效的EGFR抑制作用（分别为0.08±0.002µM和0.09±0.002µM），与厄洛替尼（0.11±0.003µM）相比。然而，没有一种化合物表现出有效的ARO抑制活性，因为测试化合物的活性比莱特罗佐尔要低。诱导凋亡能力的结果表明，在用4a、7h、9、12e和12f处理MCF-7细胞时，通过对caspase-9蛋白水平的显著刺激（4.25-7.04倍），引发了凋亡。相反，通过用4d、7a、12b和12c处理MDA-MB-231细胞，显著增加了caspase-9水平（2.32-4.06倍）。细胞周期阻滞和annexin-V/Propidium碘酸盐测定进一步证实了凋亡，因为测试化合物在各个阶段阻滞了细胞周期，并展现了高的annexin V结合亲和力。对接结果证明，化合物4d和7h与EGFR酶具有有价值的结合亲和力，而化合物4a和12e通过对接到ARO的活性位点时，未能与血红素相互作用，表明它们无法作为AI。因此，这些苯并噁唑可以作为有前途的候选物，表现出EGFR抑制和促进凋亡的特性。 版权所有©2023 Elsevier Inc.

Novel series of benzoxazole-appended piperidine derivatives were planned, synthesized and screened against two breast cancer cell lines. Considerable antiproliferative activity was observed for screened compounds (IC50 = 33.32 ± 0.2 µM to 7.31 ± 0.43 µM and 1.66 ± 0.08 µM to 12.10 ± 0.57 µM) against MCF-7 and MDA-MB-231 cell lines respectively being more potent than doxorubicin (IC50 = 8.20 ± 0.39 µM and 13.34 ± 0.63 µM respectively). Active compounds were submitted for enzyme inhibition assays when 4d and 7h demonstrated potent EGFR inhibition (0.08 ± 0.002 µM and 0.09 ± 0.002 µM respectively) compared to erlotinib (0.11 ± 0.003 µM). However, no one compound displayed effective ARO inhibition activity as tested compounds were less active than letrozole. Apoptosis inducing ability results implied that apoptosis was provoked by significant stimulation of caspase-9 protein levels (4.25-7.04-fold) upon treatment of MCF-7 cells with 4a, 7h, 9, 12e and 12f. Alternatively, MDA-MB-231 cells treated with 4d, 7a, 12b and 12c considerably increased caspase-9 levels (2.32-4.06-fold). Cell cycle arrest and annexin-V/Propidium iodide assays further confirmed apoptosis when tested compounds arrested cell cycle at various phases and demonstrated high annexin V binding affinity. Docking outcomes proved valuable binding affinities for compounds 4d and 7h to EGFR enzyme while compounds 4a and 12e, upon docking into the active site of ARO, failed to interact with heme, suggesting their inabilities to act as AIs. Therefore, these benzoxazoles can act as promising candidates exhibiting EGFR inhibition and apoptosis-promoting properties.Copyright © 2023 Elsevier Inc. All rights reserved.