Structural Optimization, Anti-TNBC Activities Evaluation, Molecular Docking and DFT Study of Indolone Derivative From Periplaneta americana

Abstract In our previous work, an indolone derivative ZL170 were isolated and identified from Periplaneta americana (P. americana). Based on its characteristic structure, we used it as lead compound to carry out structural optimization and subsequent antitumor activity evaluation. In the present study, a series of novel indolone derivatives bearing thiazole scaffold were designed and synthesized, and their antitumor activities against triple-negative breast cancer (TNBC) were determined. The preliminary screening results showed that LJ3, LJ8, LJ23, and LJ27 display inhibition rates of over 60% against MDA-MB-231cell at the concentration of 50 µM. Notably, LJ23 demonstrated an IC50 value of 32.19 µM against MDA-MB-231, prompting further evaluation of its inhibitory effect on TNBC cell motility. Results revealed that LJ23 effectively hindered TNBC cell migration through downregulation of the EMT Process. Additionally, molecular docking was employed to predict the interaction mode between LJ23 and phosphoinositide 3-kinase (PI3K). Finally, theoretical calculations were conducted for LJ23 at the B3LYP/6-31G (d, p) level, and the frontier orbital energy was discussed.