Studies on New Imidazo[2,1-b][1,3,4]thiadiazole Derivatives: Molecular Structure, Quantum Chemical Computational, and In silico Study of Inhibitory Activity Against Pim-1 Protein by using Molecular Modelling Methods and ADMET Profiling

Cyanopyridinone- and Cyanopyridine-Based Cancer Cell Pim-1 Inhibitors: Design, Synthesis, Radiolabeling, Biodistribution, and Molecular Modeling Simulation

“…The 1 H NMR spectrum of compound 4e was characterized by the presence of the pyridine proton 5′-H that resonated completely (100%) at δ 8.83 ppm as a singlet peak, indicating aromatization of the pyridone ring and the absence of the keto−enol isomers. The structure was additionally confirmed by 13 C NMR spectroscopy that showed signals, which are determined to be in accordance with the recommended molecular structure. In mass spectrometry, for example, 4b chart, there are three consecutive peaks (Figure S13), (390.8≈391), (392.9≈393), and 395, and their relative intensity is 10:6:1; this is sharp evidence that we have a dichlorinated compound.…”

“…pyridinone-H, 92%), 7.62 (dd,1H, J = 8.3 Hz, J =1.9 Hz, 6″-H), 7.67 (d, 1H, J = 8.3 Hz, 5″-H), 7.77 (dt, 1H, J = 7.0 Hz, J = 1.5 Hz, 6-H), 7.87 (d, 1H J = 1.8 Hz, 3″-H), 7.95 (dt, 1H, J = 8.5 Hz, J = 1.5 Hz, 7-H), 8.07 (d, 1H, J = 8.4 Hz, 8-H), 8.15 (d, 1H, J = 7.9 Hz, 5-H), 8.30 (s, 1H, pyridine-H, 8%), 8.74(s, 1H, 4-H), 12.24 (s, 1H, OH exchangeable by D 2 O). 13…”

“…It has been reported to be overexpressed in several types of solid cancers such as prostate as well as hematological cancers such as leukemia, multiple myeloma, and diffuse large B cell lymphomas (DLBCL). , Downregulation of Pim-1 expression by Pim-1 inhibitors has been reported to cause cell cycle arrest and increase apoptosis in some types of cancer including prostate, breast, colon, hepatic, and pancreatic cancers through different pathways, making it an attractive therapeutic target in cancer therapy. Many reported studies are concerned with discovering various classes of heterocyclic and fused heterocyclic compounds to target and inhibit Pim-1 kinase as a promising tool for fighting cancer. − Among different recognized classes, 3-cyanopyridine-based compounds are known to have significant cytotoxic effects owing to their ability to interact with different types of biological targets including the Pim-1 kinase enzyme. − For example, 6-(5-bromo-2-hydroxy) phenyl-2-oxo-4-phenyl-3- pyridine carbonitrile A (VRV) , compound B , compound C , and compound D (Figure ) have been found to be inhibitors of Pim-1 kinase. Furthermore, cyanopyridine derivatives with higher lipophilic properties as in compound E (CLogP: 4.49652) , (Figure ) inhibit survivin, which is highly expressed in most human tumors .…”

“…13 C NMR (125 MHz, DMSO-d 6 ); δ 108.7(C-3′), 114.9(CN), 121.5(C-5′), 126.6(C-6), 128.2(C-4″, C-2″), 128.3(C-6″), 128.9(C-8), 129.1(C-3″), 129.5(C-5″), 129.8(C-7, C-4a), 132.2(C-5), 133.0(C-3), 135.6(C-4), 141.3(C-1″), 147.0(C-8a), 147.7(C-2), 152.1(C-2′), 153.3(C-4′), 160.0(C-6′).…”

Bioinformática Aplicada Às Ciências Ômicas: Uma Breve Revisão Bibliográfica

“…Essa avaliação é realizada através de ferramentas in silico, utilizadas para a seleção das moléculas virtuais mais promissoras. Existe uma diversidade de softwares, que fornecem acesso para prever propriedades físico-químicas e farmacocinéticas, que demonstraram uma forte correlação linear entre os valores previstos e experimentais (KHAMEES et al, 2022).…”