269747-25-3Relevant academic research and scientific papers
Peptide dendrimers with non‐symmetric bola structure exert long term effect on glioblastoma and neuroblastoma cell lines
Sowińska, Marta,Szeliga, Monika,Morawiak, Maja,Ziemińska, El?bieta,Zab?ocka, Barbara,Urbańczyk‐lipkowska, Zofia
, p. 1 - 24 (2021)
Background: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system (CNS). Neuroblastoma (NB) is one of the most common cancers of childhood derived from the neural crest cells. The survival rate for patients with GBM and high‐risk NB is poor; therefore, novel therapeutic approaches are needed. Increasing evidence suggests a dual role of redox‐active compounds in both tumorigenesis and cancer treatment. Therefore, in this study, polyfunctional peptide‐based dendrimeric molecules of the bola structure carrying residues with antiproliferative potential on one side and the antioxidant residues on the other side were designed. Methods: We synthesized non‐symmetric bola dendrimers and assessed their radical scavenging potency as well as redox capability. The influence of dendrimers on viability of rat primary cerebellar neurons (CGC) and normal human astrocytes (NHA) was determined by propidium iodide staining and cell counting. Cytotoxicity against human GBM cell lines, T98G and LN229, and NB cell line SH‐SY5Y was assessed by cell counting and colony forming assay. Results: Testing of CGC and NHA viability allowed to establish a range of optimal dendrimers structure and concentration for further evaluation of their impact on two human GBM and one human NB cell lines. According to ABTS, DPPH, FRAP, and CUPRAC antioxidant tests, the most toxic for normal cells were dendrimers with high charge and an excess of antioxidant residues (Trp and PABA) on both sides of the bola structure. At 5 μM concentration, most of the tested dendrimers neither reduced rat CGC viability below 50–40%, nor harmed human neurons (NHA). The same dose of compounds 16 or 22, after 30 min treatment decreased the number of SH‐SY5Y and LN229 cells, but did not affect the number of T98G cells 48 h post treatment. However, either compound significantly reduced the number of colonies formed by SH‐SY5Y, LN229, and T98G cells measured 14 days after treatment. Conclusions: Peptide dendrimers with non‐symmetric bola structure are excellent scaffolds for design of molecules with pro/antioxidant functionality. Design of molecules with an excess of positive charges and antioxidant residues rendered molecules with high neurotoxicity. Single, 30 min exposition of the GBM and NB cell lines to the selected bola dendrimers significantly suppressed their clonogenic potential.
Selective Late-Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry-BF4
Gómez-Palomino, Alejandro,Cornella, Josep
supporting information, p. 18235 - 18239 (2019/11/13)
Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry-BF4), with nucleophiles. This simple reagent activates the poorly nucleophilic NH2 group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special attention has been focused on the direct conversion of densely functionalized primary sulfonamides by a late-stage formation of the corresponding sulfonyl chloride. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides, sulfonates, sulfides, sulfonyl fluorides, and sulfonic acids. The mild reaction conditions and the high selectivity of Pyry-BF4 towards NH2 groups permit the formation of sulfonyl chlorides in a late-stage fashion, tolerating a preponderance of sensitive functionalities.
A general and mild two-step procedure for the synthesis of aryl and heteroaryl sulfonamides from the corresponding iodides
Ho, Danny K.H.,Chan, Lily,Hooper, Alice,Brennan, Paul E.
, p. 820 - 823 (2011/03/18)
A mild two-step preparation of aryl and heteroaryl sulfonyl chlorides and sulfonamides from their corresponding iodides is developed. Acid labile functionalities are shown to be stable under both the copper-catalysed coupling and the subsequent oxidative chlorination.
