Costas Lago, María CarmenVila, NoemíRahman, AdeyemiBesada Pereira, PedroRozas, IsabelBrea Floriani, José ManuelLoza García, María IsabelGonzález Romero, ElisaTerán Moldes, María del Carmen2026-01-142026-01-142022-02-10María Carmen Costas-Lago, Noemí Vila, Adeyemi Rahman, Pedro Besada, Isabel Rozas, José Brea, María Isabel Loza, Elisa González-Romero, and Carmen Terán ACS Medicinal Chemistry Letters 2022 13 (3), 463-469 DOI: 10.1021/acsmedchemlett.1c00633https://hdl.handle.net/10347/45122Novel aryl guanidinium analogues containing the pyridazin-3(2H)-one core were proposed as minor groove binders (MGBs) with the support of molecular docking studies. The target dicationic or monocationic compounds, which show the guanidium group at different positions of the pyridazinone moiety, were synthesized using the corresponding silyl-protected pyridazinones as key intermediates. Pyridazinone scaffolds were converted into the adequate bromoalkyl derivatives, which by reaction with N,N’-di-Boc-protected guanidine followed by acid hydrolysis provided the hydrochloride salts 1–14 in good yields. The ability of new pyridazin-3(2H)-one-based guanidines as DNA binders was studied by means of DNA UV-thermal denaturation experiments. Their antiproliferative activity was also explored in three cancer cell lines (NCI-H460, A2780, and MCF-7). Compounds 1–4 with a bis-guanidinium structure display a weak DNA binding affinity and exhibit a reasonable cellular viability inhibition percentage in the three cancer cell lines studiedeng© 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Pyridazin-3(2H)-OneGuanidiniumDNAAntiproliferative activityjournal article10.1021/acsmedchemlett.1c006331948-5875open access