Search Results (12)

This study presents the synthesis of new fluorosulfate derivatives of 1,4-naphthoquinone by the SuFEx reaction. Anticancer properties of obtained compounds were studied on PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian cancer), MCF-7 (breast cancer), and Jurkat cell lines. All the studied compounds showed higher cytotoxic effects than Cisplatin. The DFT method was applied to determine the electronic structure characteristics of 1,4-naphthoquinone derivatives associated with cytotoxicity. A method of determination of 2,3-dichloro-1,4-naphthoquinone (NQ), 3-chloro-2-((4-hydroxyphenylamino)-1,4-naphthoquinone (NQ1), and 4-((3-chloro-1,4-naphthoquinon-2-yl)amino)phenyl fluorosulfate (NQS) in a pharmaceutical substance using an impregnated graphite electrode (IMGE) was developed. The morphology of the IMGE surface was studied using scanning electron microscopy (SEM). The electrochemical behavior of NQ, NQ1, and NQS was studied by cyclic voltammetry (CV) in 0.1 M NaClO₄ (96% ethanol solution) at pH 4.0 in a potential range from −1 to +1.2 V. Electrochemical redox mechanisms for the investigated compounds were proposed based on the determining main features of the electrochemical processes. Calibration curves were obtained by linear scan voltammetry in the first derivative mode (LSVFD) with the detection limit (LOD) 7.2 × 10⁻⁶ mol·L⁻¹ for NQ, 8 × 10⁻⁷ mol·L⁻¹ for NQ1, and 8.6 × 10⁻⁸ mol·L⁻¹ for NQS, respectively. Full article

Background: The incorporation of radionuclides into peptides and larger biomolecules requires efficient and sometimes biorthogonal reaction conditions, to which click chemistry provides a convenient approach. Methods: Traditionally, click-based radiolabeling techniques have focused on classical click chemistry, such as copper(I)-catalyzed alkyne-azide [3+2] cycloaddition (CuAAC), strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), traceless Staudinger ligation, and inverse electron demand Diels–Alder (IEDDA). Results: However, newly emerging click-based radiolabeling techniques, including tyrosine-click, sulfo-click, sulfur(VI) fluoride exchange (SuFEx), thiol-ene click, azo coupling, hydrazone formations, oxime formations, and RIKEN click offer valuable alternatives to classical click chemistry. Conclusions: This review will discuss the applications of these techniques in peptide radiochemistry. Full article

Early detection and treatment of cancers can significantly increase patient prognosis and enhance the quality of life of affected patients. The emerging significance of the tumor microenvironment (TME) as a new frontier for cancer diagnosis and therapy may be exploited by radiolabeled tracers for diagnostic imaging techniques such as positron emission tomography (PET). Cancer-associated fibroblasts (CAFs) within the TME are identified by biomarkers such as fibroblast activation protein alpha (FAPα), which are expressed on their surfaces. Targeting FAPα using small-molecule ¹⁸F-labeled inhibitors (FAPIs) has recently garnered significant attention for non-invasive tumor visualization using PET. Herein, two potent aryl-fluorosulfate-based FAPIs, 12 and 13, were synthetically prepared, and their inhibition potency was determined using a fluorimetric FAP assay to be IC₅₀ 9.63 and 4.17 nM, respectively. Radiofluorination was performed via the sulfur [¹⁸F]fluoride exchange ([¹⁸F]SuFEx) reaction to furnish [¹⁸F]12 and [¹⁸F]13 in high activity yields (AY) of 39–56% and molar activities (A_m) between 20–55 GBq/µmol. In vitro experiments focused on the stability of the radiolabeled FAPIs after incubation with human serum, liver microsomes and liver cytosol. Preliminary PET studies of the radioligands were performed in healthy mice to investigate the in vivo biodistribution and ¹⁸F defluorination rate. Fast pharmacokinetics for the FAP-targeting tracers were retained and considerable bone uptake, caused by either ¹⁸F defluorination or radioligand accumulation, was observed. In summary, our findings demonstrate the efficiency of [¹⁸F]SuFEx as a radiolabeling method as well as its advantages and limitations with respect to PET tracer development. Full article

SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external, activation-free general labelling tag. Here, we report the synthesis and characterization of a small sulfonyl fluoride library that yielded the 3-carboxybenzenesulfonyl fluoride warhead for tagging tractable targets at nucleophilic residues. Based on these results, we propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. SuFBits will label the target if it binds to the core fragment, which facilitates the identification of weak fragments by mass spectrometry. Full article

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy₃)₂/2PCy₃ as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with C_Ar-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3–10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone. Full article

Efficient ¹⁸F-fluorination procedures for the production of radiopharmaceuticals are urgently needed to satisfy the increasing demand for clinical diagnostics using positron emission tomography (PET). However, the development of PET tracers is often a time-consuming and challenging process. This work examines the applicability of the recently described sulfur [¹⁸F]fluoride exchange ([¹⁸F]SuFEx) chemistry as a fast screening approach towards a number of clinically relevant PET tracer preparations. The preparation of a number of ¹⁸F-labeled compounds commenced with [¹⁸F]fluoride loading onto a quarternary methylammonium (QMA) cartridge, which was eluted with a methanolic solution containing a base, followed by solvent removal under reduced pressure. Thereafter, the radiolabeling precursors in MeCN were added to the reaction vessels, and allowed to react via [¹⁸F]SuFEx at room temperature for 5 min. The radiofluorination reactions were quenched by water dilution followed by C18 cartridge purification. The ¹⁸F-labeled products were isolated by elution from the cartridge with EtOH and the identities of the products were confirmed by radio-ultra high performance liquid chromatography (UHPLC). The optimized preparations of ¹⁸F-labeled prostate-specific membrane antigen (PSMA) inhibitor, Programmed death-ligand 1 (PD-L1) ligand, cyclooxygenase-2 inhibitor (COXIB), and Fibroblast activation protein alpha inhibitor (FAPI) were achieved with high non-decay corrected isolated activity yields (AY) of 33–57% (n = 12) and >95% radiochemical purity (RCP) in 25 min. The automated radiosynthesis procedures afforded the radiolabeled products in an unoptimized 8–15% AY (n = 5), with >95% RCP in 40 min. The ultra-fast [¹⁸F]SuFEx reaction permitted several structurally diverse ¹⁸F-labeled compounds for potential imaging to be rapidly achieved in excellent isolated AYs and high RCP. Presently, optimization of the automated radiosynthesis and biological assessment of the ¹⁸F-labeled products is underway. Full article

A major obstacle to the therapeutic application of an aptamer is its susceptibility to nuclease digestion. Here, we confirmed the acquisition of relative nuclease resistance of a DNA-type thrombin binding aptamer with a warhead (TBA₃) by covalent binding to a target protein in the presence of serum/various nucleases. When the thrombin-inhibitory activity of TBA₃ on thrombin was reversed by the addition of the complementary strand, the aptamer was instantly degraded by the nucleases, showing that the properly folded/bound aptamer conferred the resistance. Covalently binding aptamers possessing both a prolonged drug effect and relative nuclease resistance would be beneficial for in vivo translational applications. Full article

Novel polymeric MacMillan catalysts were prepared from modified chiral imidazolidin-4-one monomers via sulfur(VI) fluoride exchange chemistry. The resulting polysulfates containing chiral imidazolidin-4-one units could be employed as polymeric organocatalysts for the asymmetric Diels–Alder reaction. With the use of these polysulfate catalysts, sufficient catalytic activity and enantioselectivity were obtained, which were similar to those obtained by monomeric catalysts in a homogeneous catalytic reaction. In addition, the polysulfate catalysts could be recovered and reused five times without a considerable loss of activity and selectivity. Full article

The fluorosulfate derivatives of benzoxazole attract attention since benzoxazole-based compounds have a wide range of biological activities, and the ability of the –SO₂F group to react with various functional groups makes it possible to synthesize various new derivatives. The new 2-(2-(fluorosulfonyloxy)phenyl)benzoxazole (2) has been synthesized by the SuFEx click reaction in a two-chamber reactor. Compound 2 is the first example of a benzoxazole derivative with a fluorosulfate-containing substituent at position two of the benzoxazole heterocycle. The anti-cancer potency of 2 was evaluated in silico using molecular docking. The docking results suggest that title compound 2 is of great interest for further studies as a possible anaplastic lymphoma kinase inhibitor. Full article

Supramolecular hydrogels are considered promising drug carriers in the tissue engineering field due to their versatile nature. Chitosan hydrogels without chemical cross-linkers have low cytotoxicity and good delivery capacity; however, they have lower mechanical properties for injectable hydrogel usage. In this study, we developed novel chitosan derivatives via click chemistry for fabricating supramolecular hydrogels with higher mechanical strength under mild conditions. The chitosan derivative was successfully synthesized by a sulfur fluoride exchange reaction, and the synthesized chitosan-mPEG/Pluronic-F127 (CS-mPEG/F127) interacted with α-cyclodextrin (α-CD) to form a supramolecular hydrogel via a host-guest reaction. The gelation dynamics, hydrogel properties, and bovine serum albumin (BSA) release could be modulated by the concentration ratio of chitosan-mPEG and F127. This supramolecular hydrogel is a promising protein releasing carrier candidate for long term regeneration therapy. Full article