Phenothiazines Modified with the Pyridine Ring as Promising Anticancer Agents

Abstract

Azaphenothiazines are the largest and most perspective group of modified phenothiazines, and they exhibit variety of biological activities. The review sums up the current knowledge on the anticancer activity of isomeric pyridobenzothiazines and dipyridothiazines, which are modified azaphenothiazines with one and two pyridine rings, respectively, against 10 types of cancer cell lines. Some 10-substituted dipyridothiazines and even 10-unsubstituted parent compounds, such as 10H-1,9-diazaphenothiazine and 10H-3,6-diazaphenothiazine, exhibited very potent action with the IC50 values less than 1 µg/mL and 1 µM against selected cancer cell lines. The strength of the anticancer action depends both on the tricyclic ring scaffolds and the substituents at the thiazine nitrogen atom. The review discusses the kind of the substituents, nature of tricyclic ring scaffolds with the location of the azine nitrogen atoms, the types of the cancer cell lines, and the mechanism of action.

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

“…Morak-Młodawska and group has been meticulously working on phenothiazines and azaphenothiazines [277][278][279] and as a matter of fact have also evaluated the lipophilicity of the synthesized derivatives. They determined the lipophilicities of the synthesized compounds theoretically by using various computations protocols, while the experimental results were obtained by reversed-phase thin-layer chromatography (RP-TLC).…”

Lipophilicity and Pharmacokinetic Properties of New Anticancer Dipyridothiazine with 1,2,3-Triazole Substituents

“…Dipyridothiazines are modified phenothiazine structures into which two pyridine rings have been introduced instead of two benzene rings [13]. In recent years, significant and highly promising anticancer activities of these heterocyclic systems have been proven [14][15][16][17]. Additionally, selected derivatives of this group showed immunomodulatory and antioxidant potential [18,19].…”

Antioxidant Properties of New Phenothiazine Derivatives

“…In wide medical practice, phenothiazine derivatives are also successfully used as antihistamines [ 6 ]. In addition, their antibacterial, antitumor, and antituberculosis effects are known [ 7 , 8 , 9 , 10 , 11 , 12 ]. The synthesis of new phenothiazine derivatives is still ongoing.…”