Beilstein Journal of Organic Chemistry published new progress about Antitumor agents. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Safety of 1,2-Di(pyridin-2-yl)disulfane.
Kufka, Rainer; Rennert, Robert; Kaludjerovic, Goran N.; Weber, Lutz; Richter, Wolfgang; Wessjohann, Ludger A. published the artcile< Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells>, Safety of 1,2-Di(pyridin-2-yl)disulfane, the main research area is breast colon prostate cancer tubugi 1 toxin neuropeptide Y; PDC; Ugi reaction; drug targeting; neuropeptide Y; peptide–drug conjugate; targeted tumor therapy; tubugi; tubulysin A.
Tubugi-1 is a small cytotoxic peptide with picomolar cytotoxicity. To improve its cancer cell targeting, it was conjugated using a universal, modular disulfide derivative This allowed conjugation to a neuropeptide-Y (NPY)-inspired peptide [K4(C-βA-),F7,L17,P34]-hNPY, acting as NPY Y1 receptor (hY1R)-targeting peptide, to form a tubugi-1-SS-NPY disulfide-linked conjugate. The cytotoxic impacts of the novel tubugi-1-NPY peptide-toxin conjugate, as well as of free tubugi-1, and tubugi-1 bearing the thiol spacer (liberated from tubugi-1-NPY conjugate), and native tubulysin A as reference were investigated by in vitro cell viability and proliferation screenings. The tumor cell lines HT-29, Colo320 (both colon cancer), PC-3 (prostate cancer), and in conjunction with RT-qPCR analyses of the hY1R expression, the cell lines SK-N-MC (Ewing′s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chem. transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic potency of the liberated tubugi-1 that, however, still bears the thiol spacer (tubugi-1-SH) was restored and up to 10-fold higher compared to the entire peptide-toxin conjugate. The conjugate shows toxic selectivity to tumor cell lines overexpressing the hY1R receptor subtype like, e.g., the hard to treat triple-neg. breast cancer MDAMB- 468 cells.
Beilstein Journal of Organic Chemistry published new progress about Antitumor agents. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Safety of 1,2-Di(pyridin-2-yl)disulfane.
Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem