Domino protocol for the synthesis of diversely functionalized derivatives of a novel fused pentacyclic antioxidant/anticancer fluorescent scaffold: Pyrazolo[5'',1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxaline

Abstract

Rising to the challenge of formidable multi-step reaction needed for the synthesis of polycyclic compounds, an efficient one-pot two-step procedure for the synthesis of densely functionalized novel pyrazolo[5″,1'':2′,3']pyrimido[4′,5':5,6] [1,4]thiazino[2,3-b]quinoxalines from synthetically accessible starting materials 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5-a]pyrimidine, 3-aminoquinoxaline-2-thiol and some readily accessible alkyl halides was established. The domino reaction pathway involves cyclocondensation/N-alkylation sequence in K2CO3/N,N-dimethyl formamide under heating condition. DPPH free radical scavenging activity of all synthesized pyrazolo[5″,1'':2′,3']pyrimido[4′,5':5,6][1,4]thiazino[2,3-b]quinoxalines was evaluated to determine their antioxidant potentials. IC50 values were recorded in the range of 29–71 μM. N-benzyl substituted derivative represented the most effective antioxidant activity as well as antiproliferative activity against MCF-7 cells. Moreover, fluorescence in solution for these compounds exhibited strong red emission in the visible region (λflu. = 536–558 nm) with good to excellent quantum yields (61–95%). Due to their interesting fluorescence properties, these novel pentacyclic fluorophores can be used as fluorescent markers and probes for studies in biochemistry and pharmacology.