Synthesis and DPPH radical-scavenging activity of some new 5-(N-substituted-1H-indol-3-yl)-5H-thiazolo[4,3-b]-1,3,4-thiadiazole derivatives

Heba M. Abo-Salem¹, Manal Sh. Ebaid¹, Eslam R. El-Sawy¹, Abd El-Nasser El-Gendy², Adel H. Mandour^1
1 Chemistry Department of Natural Compounds, National Research Centre, Dokki, Giza, Egypt
² Medicinal and Aromatic Plants Department, National Research Centre, Dokki, Giza, Egypt

Correspondence Address:
Eslam R. El-Sawy
Chemistry Department of Natural Compounds, National Research Centre, Dokki 12311, Giza
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.7123/01.EPJ.0000426585.93667.87

Heterocyclic systems with thiadiazole nucleus show a wide spectrum of biological activities such as antioxidant, analgesic, antitumor, and anti-inflammatory activities. The aim of this study is to describe the synthesis of some new 5-(N-substituted-1H-indol-3-yl)-5H-thiazolo[4,3-b]-1,3,4-thiadiazole derivatives and to evaluate their antioxidant activity using 2,2º-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity.

A one-pot reaction of N-substituted-1H-indol-3-carboxaldehyde 1a,b with thioglycolic acid and thiosemicarbazide in concentrated sulfuric acid yielded novel 2-amino-5-(N-substituted-1H-indol-3-yl)-5H-thiazolo[4,3-b]-1,3,4-thiadiazoles 2a,b. The reaction of 2a,b with some benzenesulfonyl chlorides and/or benzoyl chlorides yielded sulfonamides 3a,b and 4a,b and benzamide 5a,b and 6a,b derivatives, respectively, whereas, the reaction of 2a,b with chloroacetyl chloride yielded chloroacetamide derivatives 7a,b, which, on cyclization with potassium thiocyanate, yielded thiazolidinone derivatives 8a,b. The reaction of 2a,b with sodium azide yielded tetrazole derivatives 9a,b. However, the reaction of 2a,b with benzaldehyde yielded Schiff bases 10a,b, which cyclized with chloroacetyl chloride and/or phenacyl bromide to yield azetidinone derivatives 11a,b and 12a,b, respectively. However, the reaction of 10a,b with sodium cyanide, followed by acid hydrolysis yielded the α-amino acid derivatives 14a,b. Diazotization of 2a,b yielded diazonium salt A, which, on coupling with sodium azide, yielded the azido derivatives 15a,b. Cyclization of 15a,b with ethylacetoacetate yielded tetrazole derivatives 16a,b, whereas the coupling reaction of A with malononitrile yielded dicyano derivatives 17a,b, which, on cyclization with hydrazine hydrate, yielded 3,5-diaminopyrazole derivatives 18a,b. The newly synthesized compounds were screened for their antioxidant activity using 2,2º-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity.

4-{5-[(1H-Indol-3-yl)-5H-thiazolo[4,3-b]-1,3,4-thiadiazol-2-yl]diazo}-1H-pyrazole-3,5-diamine (18a) was highly active with radical-scavenging activity (IC50 of 69.14 μg/ml) compared with ascorbic acid (IC50 of 6.50 μg/ml).