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 of potassium carbonate (K2CO3) yielded new alkylsulfanylpyridazino[4,5-b]indole derivatives (i.e., compounds 4–6). Hydrazinolysis of ester 6 resulted in hydrazide 7. The structure of compound 6 was verified by X-ray single-crystal analysis. Among the synthesized compounds, compound 6 exhibited the most promising cytotoxicity toward MCF-7 cells with an IC50 value of 12 µM. It showed potential inhibition activity toward EGFR, PI3K, and AKT in MCF-7 cells, with 0.26-, 0.49-, and 0.31-fold reductions in concentration compared to an untreated c…