In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.
Considering a novel series of zidovudine (AZT) derivatives encompassing selenoaryl moieties promising candidates as therapeutics, we examined the toxicities elicited by AZT and derivatives 5'-(4-Chlorophenylseleno)zidovudine (SZ1); 5'-(Phenylseleno)zidovudine (SZ2); and 5'-(4-Methylphenylseleno)zidovudine (SZ3) in healthy cells and in mice. Resting and stimulated cultured human peripheral blood mononuclear cells (PBMCs) were treated with the compounds at concentrations ranging from 10 to 200 µM for 24 and/or 72 h. Adult mice received a single injection of compounds (100 µmol/kg, s.c.) and 72 h after administration, hepatic/renal biomarkers were analyzed. Resting and stimulated PBMCs exposed to SZ1 displayed loss of viability, increased reactive species production, disruption in cell cycle, apoptosis and increased transcript levels and production of pro-inflammatory cytokines. In a mild way, most of these effects were also induced by SZ2. AZT and SZ3 did not cause significant toxicity towards resting PBMCs. Differently, both compounds elicited apoptosis and S phase arrest in stimulated cells. AZT and derivatives administration did not change the body weight and plasma biochemical markers in mice. However, the absolute weight and organ-to-body weight ratio of liver, kidneys and spleen were altered in AZT, SZ1-, and SZ2-treated mice. Our results highlighted the involvement of derivatives SZ1 and SZ2 in redox and immunological dyshomeostasis leading to activation of apoptotic signaling pathways in healthy cells under different division phases. On the other hand, the derivative SZ3 emerged as a promising candidate for further viral infection/antitumor studies as a new effective therapy with low toxicity for immune cells and after acute in vivo treatment.
Xanthomonas campestris pv. campestris (Xcc) is a phytopathogenic bacteria, and it is the causative agent of black rot in crucifers. Recent studies have shown that Bacillus species have strong biological control on Xanthomonas. One of the mechanisms of this control is secondary metabolites production. A collection of 257 bacteria isolated from a suppressive soil was evaluated for in vitro antagonistic activity against X. campestris, and 92 isolates (44.6%) were able to inhibit its growth. Among the 92 isolates evaluated in the double‐layer technique, 51 (55.43%) inhibited Xcc growth on the inhibition tests with cell‐free filtrates (CFF) in liquid medium. Thirteen of these isolates presented 50% or more growth inhibition, and five isolates presented 100% growth inhibition of Xcc. The CFF of the isolate TCDT‐08, which belongs to the Paenibacillus genus, was used for in vivo tests with kale crops. The artificial inoculation of kale with Xcc‐629IBSBF pretreated with CFF from the isolate TCDT‐08 demonstrated that the bacterium loses the ability of colonizing kale and of causing black rot. A Paenibacillus sp. isolate has strong inhibitory activity against X. campestris pv. campestris, and further studies can result in the use of this isolate to protect kale from Xcc infection.
Aiming at providing an efficient and versatile method for the diversity-oriented decoration and ligation of fullerenes, we report the first C derivatization strategy based on isocyanide-multicomponent reactions (I-MCRs). The approach comprises the use of Passerini and Ugi reactions for assembling pseudo-peptidic scaffolds (i.e., N-alkylated and depsipeptides, peptoids) on carboxylic acid-functionalized fullerenes. The method showed wide substrate scope for the oxo and isocyanide components, albeit the Ugi reaction proved efficient only for aromatic amines. The approach was successfully employed for the ligation of oligopeptides and polyethyleneglycol chains (PEG) to C , as well as for the construction of bis-antennary as well as PEG-tethered dimeric fullerenes. The quantum yields for the formation of O was remarkable for the selected compounds analyzed.
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