Antioxidant Activity of Newly Synthesized 2,7‐Diazaphenothiazines

Abstract

A series of 19 derivatives of 2,7-diazaphenothiazine was synthesized and evaluated for their antioxidant activity bearing in mind the structural similarity with "classical" phenothiazines several of which are considered powerful antioxidants. Among the new derivatives that inhibited in vitro Fe(2+)/ascorbate-induced lipid peroxidation of rat liver microsomal membranes, several exhibited significant antioxidant activity with IC(50 )values in the range of 64-125 microM. Although N-substitution led to a variable degree of antioxidant activity, the latter appears to correlate with the lipophilicity (expressed as clogP values) of the substituted derivatives. Reduced lipophilicity may also explain the relatively lower protection offered by these derivatives against lipid peroxidation when compared to their "classical" phenothiazine counterparts. Thus, modification of the phenothiazine structure by a substitution of two benzene rings with pyridine rings to form this new type of azaphenothiazines does not enhance antioxidant activity, although it retains it.

3,6-Diazaphenothiazines as potential lead molecules – synthesis, characterization and anticancer activity

“…We found new dipyridothiazines of the 1,6-, 1,8-and 2,7-diazaphenothiazine structures to exhibit promising anticancer activity against lung cancers HOP-62 and HOP-92, colon cancers COLO 205, HCT-116 and SW-948, renal cancers RXF393 and A498, and leukemia HL-60(TB) and L-1210 20,21 . 10H-2,7diazaphenothiazine also shows immunosuppressant, inhibiting both humoral and cellular immune responses, and antioxidant properties [22][23][24] .…”

Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents

“…About 40 types of azaphenothiazines are known as monoaza-, diaza-, triaza-, and tetraazaphenothiazines and their monobenzo-and dibenzo derivatives 16 . Some of these azaphenothiazines being pyridobenzothiazines [17][18][19][20][21] , pyrimidobenzothiazines 22,23 , pyrazinobenzothiazines 24,25 , dipyridothiazines [26][27][28][29][30] , quinobenzothiazines [31][32][33][34][35][36] , quinobenzothiazinium salts [37][38][39] , diquinothiazines 26,27 , and quinonaphthothiazines 36,40 exhibited promising anticancer, antibacterial, antiviral, immunosuppressive, antioxidative anti-inflammatory, and enzyme inhibiting activities.…”

Facile, Odourless, Quantitative Synthesis of 3‐Hydroxy‐3,4‐dihydro‐2H‐1,4‐thiazines

“…The 1,4‐thiazine (thiomorpholine) core is a recurrent structure in organic chemistry because it is present in a numerous compounds that have found application both in medicinal and pharmaceutical chemistry, as well as in chemical manufacturing. In fact, aza‐sulfur heterocycles are known to have many biological properties including antibacterial, antimicrobial, anti‐inflammatory, hepatoprotective, calcium receptor antagonist, vasopressin receptor antagonist, anticancer and antioxidant activities, and are present in hypolipidemic agents . Furthermore, 1,4‐thiazine derivatives are commonly used as stabilisers or inhibitors of carbon steel corrosion, and it is well known that this heterocyclic moiety plays an important role in numerous pigments and dyestuffs .…”