Research Article IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells Daniela C. dos Santos , 1 Jamal Rafique , 2,3 Sumbal Saba , 3 Valdelúcia M. A. S. Grinevicius , 1 Danilo W. Filho , 4 Ariane Zamoner , 5 Antonio L. Braga , 6 Rozangela C. Pedrosa , 1 and Fabiana Ourique 7 1 Laboratório de Bioquímica Experimental (LABIOEX), Departamento de Bioquímica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil 2 Instituto de Química (INQUI), Universidade Federal do Mato Grosso do Sul (UFMS), 79074-460 Campo Grande, MS, Brazil 3 Instituto de Química (IQ), Universidade Federal de Goiás-UFG, 74690-900 Goiânia, GO, Brazil 4 Departamento de Ecologia e Zoologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil 5 Laboratório de Bioquímica e Sinalização Celular (LaBioSignal), Departamento de Bioquímica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil 6 Laboratório de Síntese de Substâncias de Selênio Bioativas (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, 88040-900 SC, Brazil 7 Universidade Federal de Juiz de Fora, Departamento de Bioquímica, Centro de Ciências Biológicas, Juiz de Fora, MG, Brazil Correspondence should be addressed to Sumbal Saba; sumbal6s@gmail.com and Fabiana Ourique; fabiana.ourique@ufjf.edu.br Received 21 November 2021; Revised 1 February 2022; Accepted 4 February 2022; Published 22 March 2022 Academic Editor: Sachchida Nand Rai Copyright © 2022 Daniela C. dos Santos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2-a]pyridine derivatives and organoselenium compounds are largely used in medicinal chemistry and drug development. This study is aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine), a selenylated imidazo[1,2- a]pyridine derivative in glioblastoma cells. IP-Se-06 exhibited high cytotoxicity against A172 cells (IC 50 =1:8 μM) and selectivity for this glioblastoma cell. The IP-Se-06 compound has pharmacological properties verified in its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1 μM), IP-Se-06 induced intracellular redox state modulation with depletion of TrxR and GSH levels as well as inhibition of NRF2 protein. IP-Se-06 also decreased mitochondrial membrane potential, induced cytochrome c release, and chromatin condensation. Furthermore, IP-Se-06 induced apoptosis by decreasing levels of Bcl-xL while increasing levels of γ-H2AX and p53 proteins. Treatment with IP-Se-06 induced cell cycle arrest and showed antiproliferative effect by inhibition of Akt/mTOR/HIF-1α and ERK 1/2 signaling pathways. In addition, IP-Se-06 displayed significant inhibition of p38 MAPK and p-p38, leading to inhibition of inflammasome complex proteins (NLRP3 and caspase-1) in glioblastoma cells. These collective findings demonstrated that IP- Se-06 is a bioactive molecule that can be considered a candidate for the development of a novel drug for glioblastoma treatment. Hindawi Oxidative Medicine and Cellular Longevity Volume 2022, Article ID 3710449, 18 pages https://doi.org/10.1155/2022/3710449