Synthesis of diglycosylated (di)sulfides and comparative evaluation of their antiproliferative effect against tumor cell lines: A focus on the nature of sugar-recognizing mediators involved

Gaetano, Sonia Di; Bedini, Emiliano; Landolfi, Alfredo; Pedone, Emilia; Pirone, Luciano; Traboni, Serena; Capasso, Domenica; Iadonisi, Alfonso

doi:10.1016/j.carres.2019.107740

Cited by 11 publications

(11 citation statements)

References 23 publications

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“…Developing selective glycomimetics is, however, very challenging due to the highly conserved carbohydrate receptor domains (CRDs) in mammalian galectins. Most of the molecules synthesized to date are based on sugar scaffolds, although some non-saccharide-based compounds, as peptide-based mimetics, have also been reported [ 39 , 56 ], opening a new scenario for the design of novel galectin inhibitors for therapeutic applications.…”

Section: Resultsmentioning

confidence: 99%

More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells

Gaetano

Capasso

Delre

et al. 2021

IJMS

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Although the approved vaccines are proving to be of utmost importance in containing the Coronavirus disease 2019 (COVID-19) threat, they will hardly be resolutive as new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, a single-stranded RNA virus) variants might be insensitive to the immune response they induce. In this scenario, developing an effective therapy is still a dire need. Different targets for therapeutic antibodies and diagnostics have been identified, among which the SARS-CoV-2 spike (S) glycoprotein, particularly its receptor-binding domain, has been defined as crucial. In this context, we aim to focus attention also on the role played by the S N-terminal domain (S1-NTD) in the virus attachment, already recognized as a valuable target for neutralizing antibodies, in particular, building on a cavity mapping indicating the presence of two druggable pockets and on the recent literature hypothesizing the presence of a ganglioside-binding domain. In this perspective, we aim at proposing S1-NTD as a putative target for designing small molecules hopefully able to hamper the SARS-CoV-2 attachment to host cells.

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Section: Resultsmentioning

confidence: 99%

More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells

Gaetano

Capasso

Delre

et al. 2021

IJMS

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“…In detail, the Pt complexes and DAP(T)–OH were dissolved in DMSO at a 10 mM concentration, while cisplatin was solubilized in an aqueous solution of DMSO (10%)/NaCl (0.9%), at a 2 mM concentration [ 50 ], then diluted with growth medium until the final solution contained no more than 0.5% DMSO, well-tolerated by in vitro cell cultures. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT, Sigma Aldrich, Milano, Italy) after 48 h incubation [ 51 ]. Plates were then analyzed using a microplate reader (Enspire, Perkin Elmer, Waltham, MA, USA) at 570 nm.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Antiproliferative Activity, and DNA Binding Studies of Nucleoamino Acid-Containing Pt(II) Complexes

et al. 2020

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We here report our studies on the reaction with the platinum(II) ion of a nucleoamino acid constituted by the l-2,3-diaminopropanoic acid linked to the thymine nucleobase through a methylenecarbonyl linker. The obtained new platinum complexes, characterized by spectroscopic and mass spectrometric techniques, were envisaged to exploit synergistic effects due to the presence of both the platinum center and the nucleoamino acid moiety. The latter can be potentially useful to protect the complexes from early deactivation, as well as to facilitate their cell internalization. The biological activity of the complexes in terms of antiproliferative effects was evaluated in vitro on different cancer cell lines and healthy cells, showing the best results on human cervical adenocarcinoma (HeLa) cells along with good selectivity for cancer over normal cells. In contrast, the metal-free nucleoamino acid did not show any cytotoxicity on both normal and cancer cell lines. Finally, the ability of the novel Pt(II) complexes to bind various DNA model systems was investigated by circular dichroism (CD) spectroscopy and polyacrylamide gel electrophoresis analyses proving that the newly obtained compounds can potentially target DNA, similarly to other well-known anticancer Pt complexes, with a peculiar G-quadruplex vs. duplex selectivity.

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“…[13] Although, symmetrical disulfides can be obtained by oxidation of thiols [14] or thiol surrogates, [15] a wide variety of reaction conditions have been developed to obtain unsymmetrical disulfides. [13,16] 1-Thiosugars or carbohydrate derivatives with S-linked functionality at anomeric position exhibit significant biological activities, which include anti-tumor, [17] anti-cancer, [18] anti-paralytic activities [19] etc. They have been used in the preparation of thiooligosaccharides, [20] S-linked glycoconjugates, [21] glycodendriomers, [22] glyconanoparticles.…”

Section: Introductionmentioning

confidence: 99%

“…1‐Thiosugars or carbohydrate derivatives with S ‐linked functionality at anomeric position exhibit significant biological activities, which include anti‐tumor, [17] anti‐cancer, [18] anti‐paralytic activities [19] etc. They have been used in the preparation of thiooligosaccharides, [20] S ‐linked glycoconjugates, [21] glycodendriomers, [22] glyconanoparticles [23] .…”

Section: Introductionmentioning

confidence: 99%

Direct Synthesis of Unsymmetrical Glycosyl Disulfides from Glycosyl Bromides

Kundu

Misra

2021

Eur J Org Chem

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A significantly fast one step reaction condition has been developed for the synthesis of unsymmetrical anomeric glycosyl disulfide derivatives in excellent yield by the treatment of anomeric glycosyl bromides with a combination of carbon disulfide (CS 2 ) and sodium sulfide nonahydrate (Na 2 S • 9H 2 O) in the presence of symmetrical alkyl, aryl and glycosyl disulfides at room temperature. Exclusive formation of anomerically betadisulfides was observed under the reaction conditions. Most of the reactions are high yielding and suitable for scale-up synthesis.

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Synthesis of diglycosylated (di)sulfides and comparative evaluation of their antiproliferative effect against tumor cell lines: A focus on the nature of sugar-recognizing mediators involved

Cited by 11 publications

References 23 publications

More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells

More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells

Synthesis, Antiproliferative Activity, and DNA Binding Studies of Nucleoamino Acid-Containing Pt(II) Complexes

Direct Synthesis of Unsymmetrical Glycosyl Disulfides from Glycosyl Bromides

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