Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship

Abstract

The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure–antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells.

Design, synthesis, structure elucidation, antimicrobial, molecular docking, and SAR studies of novel urea derivatives bearing tricyclic aromatic hydrocarbon rings

“…[34][35][36] On the other hand, the electron-rich tricyclic nitrogen-sulfurcontaining heteroaromatic, phenothiazine (IUPAC name 10Hphenothiazine) is one of the most promising pharmacophores, an exceptional and versatile classes in pharmaceutical and medicinal chemistry (Figure 1). [37] The synthesis of phenothiazine and its derivatives attracted tremendous interest as could be observed from many investigators in a large number of reported publications in the last decades. In 1883, Bernthsen reported the first synthesis of phenothiazine with antiparasitic properties.…”

New betulin imine derivatives with antioxidant and selective antitumor activity

“…24 Moreover, it was demonstrated that the biosynthesis of many natural products involves imine chemistry, being responsible for their biological activities. 25,26 In the field of anticancer drugs, imine derivatives with promising activity were obtained by combining different building blocks, heteroaromatic ones, such as pyrazolopyrimidinones, 27 aza-stilbenes, 28 betalactams, 29 imidazoles, 30 tiazoles, 31 coumarins, 32 phenothiazines 33 or simple aromatic rings. 34,35 It was envisaged that the imine bond plays a key role in the anticancer activity, due to the fact that its dynamic character favors the binding of amino acids which are essential for the growth of tumor cells.…”

Design, enantioselective synthesis, and antiviral activities against potato virus Y of axially chiral thiazine derivatives

“…Thiazines represent a class of highly attractive heterocyclic scaffolds commonly found in numerous synthetic and natural products [11,12] (Figure 1A). Previous research has highlighted the diverse range of intriguing biological effects of thiazine derivatives, including antibacterial, anticancer, anti-inflammatory, antitumor, and antiviral activities [13][14][15][16][17].…”