Synthesis, stereoelectronic characterization and antiparasitic activity of new 1-benzenesulfonyl-2-methyl-1,2,3,4-tetrahydroquinolines

Abstract

The synthesis and full 3D structural characterization of nine new 1-benzenesulfonyl-2-methyl-1,2,3,4-tetrahydroquinoline derivatives are reported. These belong to a library whose rationale for the design was the previous knowledge of the biological relevant properties of both structural moieties. From protozoan antiparasitic screening, compounds 3 demonstrated interesting activity against Trypanozoma cruzi with low cytotoxicity. Besides, most compounds were moderately active against Plasmodium falciparum. Of these, 3 and 9 can be considered as lead scaffolds for further optimization. The substituent on BS did not influence the 3D structure properties and the 1H NMR spectra revealed the existence of an intramolecular weak hydrogen bond, C-H⋯O{double bond, long}S. Molecular modeling and X-ray crystallography also confirmed this finding, which is relevant to compound conformational preference.