Transition-metal-free, atom-economical cascade synthesis of novel 2-sulfonated-benzo[f][1,7]naphthyridines and their cytotoxic activities

Abstract

An efficient, transition-metal-free cascade synthetic method has been developed for new 2-aryl/heteroaryl sulfonated benzon[f],[1,7]naphthyridines. It is tert-butyl hydroperoxide (TBHP) mediated highly regioselective sulfonylation cyclization aromatization process between N-(3-arylTheteroarylprop-2-yn-1-yl)quinolin-3-amines and aryl/heteroaryl sulfonylhydrazides. This synthetic protocol offers one-step strategy for C S and C C bond formations with a broad range of functional group tolerance. It is a simple, mild, and atom-economical route for the synthesis of various valuable functionalized 1, 2-aryl/heteroaryl sulfonated benzo[f][1,7]naphthyridines in moderate yields. Since the core motif of 2-sulfonated benzo[f][1,7]naphthyridines are biologically and pharmaceutically important (TLR activity 7, 8 modulators). Additionally, the synthesized derivatives were evaluated for their in vitro cytotoxic activities against six human cancer cell lines including lung (NCIH23), colon (HCT15), gastric (NUCG-3), renal (ACHN), prostate (PC-3), and breast (MDA-MB-231) cell lines. These compounds displayed significant cytotoxic activities against all tested human cancer cell lines. (C) 2018 Elsevier Ltd. All rights reserved.