Synthesis, X-ray Single-Crystal Analysis, and Anticancer Activity Evaluation of New Alkylsulfanyl-Pyridazino[4,5-b]indole Compounds as Multitarget Inhibitors of EGFR and Its Downstream PI3K-AKT Pathway

The alkylation of 3,5-dihydro-4H-pyridazino[4,5-b]indole-4-thione with benzyl bromide, ethyl chloroacetate, and allyl bromide in the presence potassium carbonate (K2CO3) yielded new alkylsulfanylpyridazino[4,5-b]indole derivatives (i.e., compounds 4–6). Hydrazinolysis ester 6 resulted hydrazide 7. structure compound was verified by X-ray single-crystal analysis. Among synthesized compounds, exhibited most promising cytotoxicity toward MCF-7 cells an IC50 value 12 µM. It showed potential inhibition activity EGFR, PI3K, AKT cells, 0.26-, 0.49-, 0.31-fold reductions concentration compared to untreated control. Additionally, it apoptosis-inducing (47.98-fold); overall apoptosis increased 38.87% 0.81% control, which disrupted cell cycle at pre-G1 S phases. Moreover, good binding affinities tested proteins (EGFR, AKT) had energies ranging from −15.87 −24.87 Kcal/mol. also formed interactions essential amino acids inside sites. Hence, is recommended as anti-breast cancer chemotherapeutic due its effects on EGFR-PI3K-AKT pathway.