Synthetic porphyrins bearing a lateral peptide chain—V : On the lack of evidence from exafs for a short axial ZN-S bond in the case of cis-endo-3-propenamid-znTPP derivatives featuring a terminal S-alkyl cysteine residue

“Extended X-Ray Absorption Fine Structure” (EXAFS) spectroscopy has been used for probing the environment of the Zn²⁺ cation in three 3-propenamid-Zn tetraphenyporphyrin complexes. The lack of evidence for a short axial bond of the zinc atom to the sulfur atom of the cysteine terminal residue of the lateral peptidic chain is discussed, together with the few indications which suggest that a Zn-S interaction, if any, can only be weak and probably long range (4.1 Å ?).     

Introducing a new pharmaceutical agent: Facile synthesis of CuFe12O19@HAp-APTES magnetic nanocomposites and its cytotoxic effect on HEK-293 cell as an efficient in vitro drug delivery system for atenolol

In this study, novel CuFe₁₂O₁₉@hydroxyapatite magnetic nanocomposites (CuFe₁₂O₁₉@HAp MNCs) as controlled target drug delivery were synthesized by ultrasound-assisted precipitation method for the first time. Then, the magnetic substrate was functionalized with APTES (CuFe₁₂O₁₉@HAp-APTES MNCs) to increase the efficiency of the drug delivery system. The crystallinity, size, morphology, and composition of the products were determined by FESEM, DLS, BET, TEM, XRD, EDS, and VSM. In order to investigate the drug loading ability of prepared nanocomposites, we chose antihypertensive drug (atenolol) as the model drug. After that, the release behavior of magnetic nanocomposites modified atenolol was investigated under stomach (pH value of 1.5–2) and intestine (pH value of 5.8–6.7) conditions. The results revealed that the highest entrapment efficiency was achieved by CuFe₁₂O₁₉@HAp-APTES MNCs (63.1%). Furthermore, the controlled-release potential for CuFe₁₂O₁₉@HAp-APTES MNCs was the highest compared with the pure CuFe₁₂O₁₉@HAp MNCs. Increased efficiency can be due to the binding of the amine group in APTES with the atenolol drug. The cytotoxicity of the ATL-loaded magnetic nanocomposites (ATL-CuFe₁₂O₁₉@HAp-APTES MNCs) was investigated on the HEK-293 cell line using MTT assay. Based on the results, we concluded that the synthesized magnetic nanocomposites could be effective vehicles for the sustained delivery of atenolol as an antihypertensive drug.     

meso-Tetra(pentafluorophenyl)porphyrin as an efficient platform for combinatorial synthesis and the selection of new photodynamic therapeutics using a cancer cell line

The four para fluoro groups on 5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (TPPF20) are known to react with a variety of nucleophiles, but the reaction conditions for this substitution reaction depend on the nature of the nucleophiles, e.g. primary amines versus thiols. Glycosylated derivatives of this core porphyrin have been shown to be effective photodynamic agents in the induction of necrosis or apoptosis in several cancer cell lines. The present report demonstrates that TPPF20 can be used as a core platform to efficiently generate a variety of solution-phase combinatorial libraries. The focused combinatorial libraries have substituents that are chosen from a set of motifs known to bind biopolymers such as DNA, be taken up by cancer cells, or to render the compounds amphipathic. Incubation of a breast cancer cell line with these solution-phase libraries, followed by cell lyses and extraction, affords a selection assay. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the extracts allows identification of the molecules taken up by the cells. Cell binding assays of the winning compounds synthesized directly indicate that both glycosylation and amphipathicity are key properties since neither tetraglycosylated porphyrins nor those with four polar groups are selected to the same extent. In addition, photodynamic efficacy was evaluated.     

The resurrection of RIP kinase 1 as an early cell death checkpoint regulator—a potential target for therapy in the necroptosis era

Receptor-interacting serine threonine protein kinase 1 (RIPK1) has emerged as a central molecular switch in controlling the balance between cell survival and cell death. The pro-survival role of RIPK1 in maintaining cell survival is achieved via its ability to induce NF-κB-dependent expression of anti-apoptotic genes. However, recent advances have identified the pro-death function of RIPK1: posttranslational modifications of RIPK1 in the tumor necrosis factor receptor 1 (TNFR1)-associated complex-I, in the cytosolic complex-IIb or in necrosomes regulate the cytotoxic potential of RIPK1, forming an early cell death checkpoint. Since the kinase activity of RIPK1 is indispensable in RIPK3- and MLKL-mediated necroptosis induction, while it is dispensable in apoptosis, a better understanding of this early cell death checkpoint via RIPK1 might lead to new insights into the molecular mechanisms controlling both apoptotic and necroptotic modes of cell death and help develop novel therapeutic approaches for cancer. Here, we present an emerging view of the regulatory mechanisms for RIPK1 activity, especially with respect to the early cell death checkpoint. We also discuss the impact of dysregulated RIPK1 activity in pathophysiological settings and highlight its therapeutic potential in treating human diseases.Subject terms: Apoptosis, Necroptosis, Checkpoint signalling