A series of 78 synthetic 7-chloro-(4-thioalkylquinoline) derivatives were investigated for cytotoxic activity against eight human cancer as well as 4 non-tumor cell lines. The results showed, with some exceptions, that sulfanyl 5-40 and sulfinyl 41-62 derivatives exhibited lower cytotoxicity for cancer cell lines than those of well-described sulfonyl N-oxide derivatives 63-82. As for compound 81, the most pronounced selectivity (compared against BJ and MRC-5 cells) was observed for human cancer cells from HCT116 (human colorectal cancer with wild-type p53) and HCT116p53-/- (human colorectal cancer with deleted p53), as well as leukemia cell lines (CCRF-CEM, CEM-DNR, K562, and K562-TAX), lung (A549), and osteosarcoma cells (U2OS). A good selectivity was also detected for compounds 73 and 74 for leukemic and colorectal (with and without p53 deletion) cancer cells (compared to MRC-5). At higher concentrations (5 × IC50) against the CCRF-CEM cancer cell line, we observe the accumulation of the cells in the G0/G1 cell phase, inhibition of DNA and RNA synthesis, and induction of apoptosis. In addition, X-ray data for compound 15 is being reported. These results provide useful scientific data for the development of 4-thioalkylquinoline derivatives as a new class of anticancer candidates.

Department of Chemical and Environmental Science University of Limerick V94 T9PX Limerick Ireland

Dirección de Investigación Universidad ECOTEC Km 13 5 Vía Samborondón Guayaquil 092302 Ecuador

Escuela de Medicina UEES Universidad Espíritu Santo Samborondón 092301 Ecuador

Institut des Sciences Moléculaires Université de Bordeaux 351 Cours de la Libération CEDEX 33405 Talence France

Institut Universitaire de France CEDEX 05 75231 Paris France

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Czech Advanced Technology and Research Institute Palacky University Hněvotínská 1333 5 77900 Olomouc Czech Republic

Instituto de Immunologia Facultad de Medicina Universidad Central de Venezuela Los Chaguaramos 1050 A Caracas 50109 Venezuela

Laboratorio de Productos Naturales Facultad de Farmacia y Bioanálisis Universidad de Los Andes Merida 5101 Venezuela

Laboratorio de Síntesis Orgánica Facultad de Farmacia Universidad Central de Venezuela Los Chaguaramos 1041 A Caracas 47206 Venezuela

Unidad de Biotecnología Facultad de Farmacia Universidad Central de Venezuela Los Chaguaramos 1041 A Caracas 47206 Venezuela

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