《Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure-activity relationship, toxicity, and mechanism of action》 was written by da Rosa, Rafael; Dambros, Bibiana Paula; Hoehr de Moraes, Milene; Grand, Lucie; Jacolot, Maiwenn; Popowycz, Florence; Steindel, Mario; Schenkel, Eloir Paulo; Campos Bernardes, Lilian Sibelle. Application of 15854-87-2This research focused onTrypanosoma toxicity structure activity relationship; Antiparasitic; Isoxazole; Mitochondrial dysfunction; Natural products; Neglected tropical diseases; Oxazole; T. cruzi. The article conveys some information:
Chem. scaffolds of natural products have historically been sources of inspiration for the development of novel mols. of biol. relevance, including hit and lead compounds To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: THF lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T. cruzi infection. In the first series of compounds, 11 derivatives of hit compound 5 (EC50 = 1.1 μM) were found to be active; the most potent (7, 8, and 13) had EC50 values of 5.1-34.2 μM. In the second series, 17 analogs were found active at 50 μM; the most potent compounds (47, 49, 59, and 63) showed EC50 values of 24.2-49.1 μM. Active compounds were assessed for selectivity, hemocompatibility, synergistic potential, effects on mitochondrial membrane potential, and inhibitory effect on trypanothione reductase. All active compounds showed low toxicity against uninfected THP-1 cells and human erythrocytes. The potency of compounds 5 and 8 increased steadily in combination with benznidazole, indicating a synergistic effect. Furthermore, compounds 8, 47, 49, 59, and 63 inhibited parasitic mitochondria in a dose-dependent manner. Although increased reactive oxygen species levels might lead to mitochondrial effects, the results indicate that the mechanism of action of the compounds is not dependent on trypanothione reductase inhibition. In silico calculation of chem. descriptors and principal component anal. showed that the active compounds share common chem. features with other trypanocidal mols. and are predicted to have a good ADMET profile. Overall, the results suggest that the compounds are important candidates to be further studied for their potential against T. cruzi. In addition to this study using 4-Iodopyridine, there are many other studies that have used 4-Iodopyridine(cas: 15854-87-2Application of 15854-87-2) was used in this study.
4-Iodopyridine(cas: 15854-87-2) is a halogenated heterocycle that is a building block for proteomics research. 4-Iodopyridine is used as a reagent in the synthesis of indazolylamides as glucocorticoid receptor agonists.Application of 15854-87-2
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com