2-Aminothiophene derivative 8c is the prototype of a well-defined class of tumor-selective agents. Compound 8c preferentially inhibited the proliferation of a number of tumor cell lines including many human T-lymphoma/leukemia cells, but also several prostate, renal, central nervous system and liver tumor cell types. Instead, a broad variety of other tumor cell lines including B-lymphomas and HeLa cells were not affected. The tumor selectivity (TS) (selectivity index or preferential suppression of CEM lymphoma (CC50: 0.90 µM) versus HeLa tumor cell carcinoma (CC50: 39 µM)) amounted up to 43 for 8c. At higher concentrations, the compound proved cytotoxic rather than cytostatic. The antiproliferative potency and selectivity of the prototype compound could be preserved by replacing the ethyl linker between the 2-amino-3-carboxymethylthiophene and the substituted aryl by a thioalkyl but not by an oxyalkyl nor aminoalkyl. Among more than 50 novel 8c derivatives, the 5-(4-ethyl- and 4-isopropylarylmethylthio)thiophene analogues were more potent (CC50: 0.3-0.4 µM) and selective (TS: 100-144) anti-T-lymphoma/leukemia agents than the prototype compound
Structure-Activity Relationship of Tumor-Selective 5-Substituted 2-amino-3-carboxymethylthiophene Derivatives
ROMAGNOLI, Romeo;
2014
Abstract
2-Aminothiophene derivative 8c is the prototype of a well-defined class of tumor-selective agents. Compound 8c preferentially inhibited the proliferation of a number of tumor cell lines including many human T-lymphoma/leukemia cells, but also several prostate, renal, central nervous system and liver tumor cell types. Instead, a broad variety of other tumor cell lines including B-lymphomas and HeLa cells were not affected. The tumor selectivity (TS) (selectivity index or preferential suppression of CEM lymphoma (CC50: 0.90 µM) versus HeLa tumor cell carcinoma (CC50: 39 µM)) amounted up to 43 for 8c. At higher concentrations, the compound proved cytotoxic rather than cytostatic. The antiproliferative potency and selectivity of the prototype compound could be preserved by replacing the ethyl linker between the 2-amino-3-carboxymethylthiophene and the substituted aryl by a thioalkyl but not by an oxyalkyl nor aminoalkyl. Among more than 50 novel 8c derivatives, the 5-(4-ethyl- and 4-isopropylarylmethylthio)thiophene analogues were more potent (CC50: 0.3-0.4 µM) and selective (TS: 100-144) anti-T-lymphoma/leukemia agents than the prototype compoundI documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
