Ature of an oxidant applied, pH of solutions, the type and
Ature of an oxidant applied, pH of solutions, the sort and concentration of acid or buffer used, temperature and time of reaction (Borg and Cotziaz 1962; El-Gindy et al. 2002; Puzanowska-Tarasiewicz et al. 2005; Nalcz-Jawecki et al. 2008; Puzanowska-Tarasiewicz et al. 2009). The hydrolysis of phenothiazines was also described in the literature (VEGF121 Protein manufacturer Pawelczyk and Marciniec 1974; Pawelczyk et al. 1975; Egorov 1998; Nalcz-Jawecki et al. 2008). Essentially the most often reported modifications of the molecule concerned S/N-oxidation, wherein N-oxides areMed Chem Res (2017) 26:2443sirtuininhibitorFig. 4 MS fragmentaion spectrum of substrate (Flu-A) a and its photodegradation products DP I b and DP II c (FV 250 V)formed mostly by oxidation from the nitrogen atoms present in the side chain in the 10-position. Oxidation at the nitrogen atom in phenothiazine ring is significantly less likely to take place because substitution of an alkyl group in the 10-position causes oxidation at ring to be much more difficult. In Complement C5/C5a, Mouse addition transformation in the trifluoromethyl to a carboxylic group, elimination of amine side chains or dimerization is usually also observed (Pawelczyk et al. 1975; Heyes 1982; Egorov 1998; Nalcz-Jawecki et al. 2008; Trautwein and K merer 2012). According to the above literature information connected with degradation of diverse phenothiazine derivatives, the molecular formula of DP I at m/z 445 could possibly be defined as C20H23F3N2O4S along with the corresponding structure could be attributed to any oxides of Flu-A: sulfoxides or N-oxides. For unambiguous identification of DP I greater FV (250 V) was applied brought on in-source fragmentation of compound. Fragmentation ions with the phenothiazine core combined with oxygen at m/z 296 and 340, which indicates oxidation at a sulfur atom in a phenothiazine ring, were observed. In addition, MS fragments at m/z 162 and 118 exclude oxidation at an aliphatic amine side chain. On this basis the solution at m/z 445 might be attributed to a sulfoxide of FluA (DP I) (Fig. 4b). Beneath light DP II formation have been observed. MS fragmentation of DP II led to fragment ions m/z 224 and 256, which may perhaps indicate a transformation with the trifluoromethyl moiety to a carboxylic group (Fig. 4c).DP I and II eluted at earlier retention time than their parent compound, which indicates their greater polarity. This observation may possibly confirm the hypothesis that DP I (logPcalc. = 1.90; the worth calculated by ChemDraw plan) can be a sulfoxide of Flu-A (for Flu-A logPcalc. = 2.93) and DP II is really a carboxylic derivative of Flu-A (logPcalc. = 1.57).ConclusionsIn this paper stability of new fluphenazine analogue (FluA), which was developed to counteract the resistance of cancer cells to cytostatics, was investigated. Determined by the results we obtained, it was demonstrates that Flu-A in solutions is sensitive to light and oxidative agents, so the substance needs to be protected just before these variables within the future research (preformulation procedure, testing on animal models etc.). Flu-A susceptibility to oxidation and photodegradation was confirmed by HPLC-ESI-MS and degradation profile obtained.Acknowledgements This study was partly supported by Poznan University of Health-related Sciences grant 502-14-03305411-08304 and 502-01-03305411-04981.Med Chem Res (2017) 26:2443sirtuininhibitor451 Compliance with ethical standards Conflict of interest interests. The authors declare that they have no competing2451 Jaszczyszyn A, Gsiorowski K, witek P, Malinka W (2009) The effect in the newly synthesized fluphenazine analogues on.
Posted inUncategorized