ABSTRACT
A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a NËCËN 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was designed and synthesized for real-time drug delivery monitoring in cancer cells and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic effect to six cancer cell lines expressing integrins at different extent, while possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake by receptor-mediated endocytosis and efficient generation of 1O2 upon irradiation. Incubation of rat bladder cancer cells AY27 with conjugate 4 (50 µΜ) prior to blue light exposure (5 min) resulted in significant reduction (50%) of cell survival compared to control cells as measured by MTT assay post 24 h after treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Integrins/antagonists & inhibitors , Oligopeptides/pharmacology , Organoplatinum Compounds/pharmacology , Photochemotherapy , Platinum/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Integrins/metabolism , Molecular Structure , Oligopeptides/chemistry , Organoplatinum Compounds/chemical synthesis , Organoplatinum Compounds/chemistry , Platinum/chemistry , Rats , Structure-Activity RelationshipABSTRACT
An efficient method for the synthesis of spiro-N,O-ketals with 5- and 6-membered rings was developed via a gold-catalyzed spiroamidoketalization of alkynyl amidoalcohols under mild conditions. This methodology has been successfully applied to the synthesis of a spiro-N,O-ketal analogue of marineosin A.
Subject(s)
Gold/chemistry , Spiro Compounds/chemistry , Spiro Compounds/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , Models, Molecular , Molecular ConformationABSTRACT
Sumoylation is a post-translational modification involved in the regulation of several cell functions. Recent studies suggest its involvement in spermatogenesis, but occurrence and function of SUMO (small ubiquitin-like modifier) in mature spermatozoa remain unknown. We report the occurrence of several SUMO1-conjugated proteins, in a range of 20-85 kDa, in ejaculated spermatozoa. By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive spermatozoa in 58 subjects undergoing semen analysis in our laboratory and correlated the obtained values with semen parameters. We found that the percentage of SUMO1-positive spermatozoa was inversely correlated with total (r = -0.35, p < 0.01) and progressive motility (r = -0.29, p < 0.05). Such correlations become stricter when only asthenospermic subjects were included in the analysis (r = -0.58, p = 0.01 for progressive motility, n = 17) and were lost in non-asthenospermic subjects. By immunofluorescence and immunoconfocal fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy as well as a long permeabilization protocol demonstrated a massive localization of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish dead/live cells, we show that SUMO1 is mainly present in live spermatozoa. In conclusion, sumoylation of human spermatozoa may be involved in the regulation of motility.
