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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. [ABSTRACT FROM AUTHOR]

The interleukin‐2‐inducible kinase (ITK) and Bruton tyrosine kinase (BTK) are two crucial Tec family kinase members with important roles in the development of hematopoietic malignancies, autoimmune disorders and other diseases in humans. Thus, ITK and BTK are key targets for drug development. Spirooxindoles are important scaffolds for the synthesis of small molecules with broad and potent biological activities. In this study, we performed a structure‐activity relationship study of a new series of 5′‐(benzo[d][1,3]dioxol‐5‐yl)spiro[piperidine‐4,3′‐pyrrolo[2,3–b]pyridin]‐2′(1′H)‐one linked with N‐acyl and C‐5 aryl‐substituted scaffolds in a panel of ITK and BTK cancer cell lines. Four compounds 11, 12, 14, and 15 showed high antiproliferative activity against ITK and BTK cell lines. Compounds 11 and 12 with a C‐5 benzodioxole group and gem‐dialkyl group attached to carbonyl on piperidine were highly effective in ITK‐high Jurkat and CEM cell lines, and compound 14, a biotin analogue, was identified as a good inhibitor of BTK‐high RAMOS cells. Compound 15 with cyclopropyl group attached to carbonyl on piperidine also showed good activity in ITK and BTK cell lines. [ABSTRACT FROM AUTHOR]