Synthesis and Antioxidant Activity of Some New Binary Pyrazoles Containing Core Phenothiazine Moiety

Abstract

α,β‐Unsaturated ketones containing phenothiazine moiety 4, 5, and 7 were synthesized by condensation of 2‐acetylphenothiazine (1) with different aryl aldehydes 2, 3 and dimethylformamide dimethylaceal. Pyrazoles 11, 18, 20, 22, 23, 24, 25, 26, 28, 29, 31, 32 and oxazole 34 skeletons were also synthesized by 1,3‐dipolar cycloaddition reactions of α,β‐unsaturated ketones with different nucleophilic reagents. Formylpyrazole derivative 36 was synthesized through Vilsmeier–Haack reaction of phenylhydrazone 35b. Newly synthesized compounds were screened for antioxidant activity. The data showed clearly that most of the compounds anchored to phenothiazine moiety displayed good antioxidant activity using ABTS method. Furthermore, compounds 11, 14, and 28 exhibited high protection against DNA damage induced by the bleomycin iron complex.

Synthesis of Novel Chalcone-Based Phenothiazine Derivatives as Antioxidant and Anticancer Agents

“…It is also observed that the activity of the tested compounds as antioxidants was slightly dependent on the aryl ring, indicating that the potency of this class of compounds as antioxidants is mainly due to the phenothiazine ring. This result is in accordance with similar chemical antioxidant activity for the nonalkylated phenothiazine-based chalcone reported earlier [ 38 ]. It has been reported that the antioxidant activity of phenothiazine and its derivatives is due to the formation of a stable radical cation that becomes stabilized over a large conjugative moiety, and to the change of the phenothiazine butterfly structure to a planar one.…”

“…Several chalcone-based compounds have been approved for clinical use, such as metochalcone and sofalcone [ 37 ]. A few studies have been reported on chalcone-based phenothiazine [ 38 , 39 , 40 ]. In this context, a series of different N-substituted rhodamines were synthesized and evaluated for their chemotherapeutic effectiveness on antileukemia cell line K562 [ 41 ].…”

Highlights on the synthesis of novel phenothiazine‐based azines scaffold as antioxidant agents

“…Found: C: 68.83; H: 5.38; N: 9.40%. The obtained spectroscopic data agreed with those reported for this compound …”

“…The synthetic routes and mechanistic pathways for the preparations of pyridine and pyrimidine‐phenothiazine heterocyclic systems are shown in Schemes . Claisen‐Schimidt condensation, of 1‐(4a,10a‐dihydro‐10 H ‐phenothiazin‐2‐yl)ethan‐1‐one ( 1 ) with each of piperonal and 1,3‐diphenyl‐4‐formyl‐1 H ‐pyrazole , in EtOH contain sodium hydroxide yielded the respective unsaturated ketones 2 and 2a , respectively (Scheme ). 1 H NMR shows singlet signal at δ 6.16 for 2H, O–CH 2 –O, and doublet signals at 6.64 for 1H, ═CH, J = 12 Hz, and another doublet at 6.66 for 1H, CO–CH═, J = 12 Hz) beside multiple signals at 7.64‐6.70 for10H, Ar–H, and singlet signal 8.75 1H, NH)…”

“…Taking into account the mentioned findings and continuing our researches in synthesizing novel potent heterocycles of variable activities , it is reported herein the synthetic routes, structure characterization, and mechanistic pathways of phenothiazine analogs as novel antioxidant agents. The incorporation of azine heterocyclic systems into phenothiazine nucleus is useful to study the effect of these ring systems and structure relationship on the obtained antioxidant results with the hope to synthesize highly potent antioxidant compounds.…”