Phenothiazine based compounds are well known for their successful application in bio-medicine  and opto-electronics . The main issue that reduces the application area of the phenothiazine derivatives is their low solubility in ordinary solvents . To overcome this issue, this study aims to obtain new PEGylated phenothiazine derivatives with improved water solubility. To do this, a series of three new PEGylated phenothiazine derivatives were prepared by grafting PEG chains to the phenothiazine core by three different linkers: ether, ester or amide units. The structure of the targeted molecules was confirmed by NMR spectra by the occurrence of the characteristic protons in the expected ratio of their integrals, and also by the disappearing of the band at 4.59 ppm specific for hydroxyl proton from poly(ethylene glycol) reagent. Moreover, the FTIR spectra presented the characteristic bands for each compound, i.e. amide carbonyl group at 1690 cm-1 and ester carbonyl group at 1742
cm-1. The capacity of the synthetized compounds to self-assembly in water was studied by DLS and UV-vis techniques, which allowed finding the hydrodynamic diameter of the aggregates. The particularities of the formed aggregates were investigated by fluorescence spectroscopy, SEM, AFM, POM and UV light microscopy. Their biocompatibility was assessed on normal human dermal fibroblasts and five human cancer cell lines. The synthetized compounds showed the formation of luminescent aggregates with diameter in the range 60 - 700 nm and proved excellent biocompatibility on normal cells . A concentration dependent cytotoxicity against four cancer cell lines was noticed for the PEGylated phenothiazine containing an ester unit and against two cancer cell for direct PEGylated phenothiazine. In vivo anti-tumor investigations are in progress.
This work was supported by the Romanian National Authority for Scientific Research MEN – UEFISCDI (grant number PN-III-P1-1.2-PCCDI2017-0569, no. 10PCCDI/2018).
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