NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health.

PURPOSE OF REVIEW: NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in regulation pathways for energetic, genotoxic, and infectious stress. In stress conditions, NAD+ biosynthesis and levels decrease as well as the activity of consuming enzymes rises. Dietary precursors can promote NAD+ biosynthesis and increase intracellular levels, being a potential strategy for reversing physiological decline and preventing diseases. In this review, we will show the biochemistry and metabolism of NAD+ precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), the latest findings on their beneficial physiological effects, their interplay with gut microbiota, and the future perspectives for research in nutrition and food science fields. RECENT FINDINGS: NMN and NR demonstrated protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels. NR and NMN have been found in vegetables, meat, and milk, and microorganisms in fermented beverages can also produce them. NMN and NR can be obtained through the diet either in their free form or as metabolites derivate from the digestion of NAD+. The prospection of NR and NMN to find potential food sources and their dietary contribution in increasing NAD+ levels are still an unexplored field of research. Moreover, it could enable the development of new functional foods and processing strategies to maintain and enhance their physiological benefits, besides the studies of new raw materials for extraction and biotechnological development.

Multifunctional Fischer Aminocarbene Complexes as Hole or Electron Transporting Layers in Organic Solar Cells.

A new series of Fischer carbenes have been synthetized and examined as hole-transporting or electron-transporting layers (HTLs or ETLs) in the fabrication of organic solar cells (OSCs). The synthesis of three Fischer aminocarbene complexes with the general formula [Cr(CO)5{C(NHCH2)Ar}] (Ar = 2-pyridyl (3a), 3-pyridyl (3b) and 4-pyridyl (3c)) is reported. The molecular structure of complex 3b has been confirmed by X-ray analysis. In order to study the possible applications of the three Fischer aminocarbenes in OSCs, thin films of these complexes were prepared using a vacuum deposition process. These organometallic films were chemically and morphologically characterized by IR spectroscopy, SEM, AFM and XRD. According to the IR and Tauc analysis, the vacuum deposition process generates thin films free of impurities with an activation energy of 4.0, 2.7 and 2.1 eV for 3a, 3b y 3c, respectively. The UV-vis spectra of the amorphous aminocarbene films show that they are practically transparent to the visible radiation of the electromagnetic spectrum. This is due to the fact that their absorption is located mainly in the ultraviolet range. Two OSCs with bulk-heterojunction configuration were manufactured in order to prove the use of the aminocarbenes as ETL o HTL. The aminocarbene [Cr(CO)5{C(NHCH2) 4-pyridyl}] (3c) proved to be suitable as ETL with a fill factor (FF) of 0.23 and a short circuit current density (JSC) of 1.037 mA/cm².

Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death.

Chagas disease, caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. Although chemotherapy options are limited presenting serious problems, such as low efficacy and high toxicity. T. cruzi is susceptible to thiazoles, making this class of compounds appealing for drug development. Previously, thiazoles resulted in an increase in anti-T. cruzi activity in comparison to thiosemicarbazones. Here, we report the structural planning, synthesis and anti-T. cruzi evaluation of new thiazoles derivatives (3a-m and 4a-m), designed from molecular hybridization associated with non-classical bioisosterism. By varying substituents attached to the phenyl and thiazole rings, substituents were observed to retain, enhance or greatly increase their anti-T. cruzi activity, in comparison to the corresponding thiosemicarbazones. In most cases, electron-withdrawing substituents, such as bromine, 3,4-dichloro and nitro groups, greatly increased antiparasitic activity. Specifically, new thiazoles were identified that inhibit the epimastigote proliferation and were toxic for trypomastigotes without affecting macrophages viability. These compounds were also evaluated against cruzain. However, inhibition of this enzyme was not observed, suggesting that the compounds work through another mechanism. In addition, examination of T. cruzi cell death showed that these molecules induce apoptosis. In conclusion, except for compounds 3h and 3k, all thiazoles derivatives evaluated exhibited higher cytotoxic activity against the trypomastigote forms than the reference medicament benznidazole, without affecting macrophages viability. Compounds 4d and 4k were highlights, CC50 = 1.2 e 1.6 µM, respectively. Mechanistically, these compounds do not inhibit the cruzain, but induce T. cruzi cell death by an apoptotic process, being considered a good starting point for the development of new anti-Chagas drug candidates.

2,6-Bis(2,6-diethylphenyliminomethyl)pyridine coordination compounds with cobalt(II), nickel(II), copper(II), and zinc(II): synthesis, spectroscopic characterization, X-ray study and in vitro cytotoxicity.

Coordination compounds with cobalt(II), nickel(II), copper(II) and zinc(II) and the ligand 2,6-bis(2,6-diethylphenyliminomethyl)pyridine (L) were synthesized and fully characterized by IR and UV-Vis-NIR spectroscopy, elemental analysis, magnetic susceptibility and X-ray diffraction for two representative cases. These novel compounds were designed to study their activity as anti-proliferative drugs against different human cancer cell lines. The tridentate ligand forms heptacoordinated compounds from nitrate metallic salts, where the nitrate acts in a chelating form to complete the seven coordination positions. In vitro cell growth inhibition was measured for Co(II), Cu(II) and Zn(II) complexes, as well as for the free ligand. Upon coordination, the IC50 value of the transition-metal compounds is improved compared to the free ligand. The copper(II) and zinc(II) compounds are the most promising candidates for further in vitro and in vivo studies. The activity against colon and prostate cell lines merits further research, in views of the limited therapeutic options for such cancer types.