The design, synthesis and biol. evaluation of lexitropsins bearing mixed heterocyclic and benzoheterocyclic moieties and tethered to an alpha-bromo acrylic moiety acting as alkylating moiety are reported, and structure-activity relationships detd. For example, indolecarboxylic acid I reacted with pyrrole deriv. II to give analog III (X = Y = CH, Z = NMe) in 63% yield. With respect to antiproliferative activity against L1210 and K562 cells, III (X = H, Y = CH, Z = NMe; X = CH, Y = H, Z = NMe) showed the greatest potency, while III (X = Y = CH, Z = NMe, O) exhibit the lowest activity. Among the synthesized compds. III (X = CH, Y = H, Z = NMe) was found to be the most potent member of this class and it is 70-fold more active than the bis-pyrrole counterpart against L1210 cell line. In addn., the cytotoxicity of derivs. III against KB cells and the influence of different glutathione (GSH) concns. on the cytotoxic effects was also investigated.
Synthesis and biological activity of alpha-bromoacryloyl lexitropsin conjugates
ROMAGNOLI, Romeo;BARALDI, Pier Giovanni;IACONINOTO, Antonietta;AGHAZADEH TABRIZI, Mojgan;GAMBARI, Roberto;BORGATTI, Monica;
2005
Abstract
The design, synthesis and biol. evaluation of lexitropsins bearing mixed heterocyclic and benzoheterocyclic moieties and tethered to an alpha-bromo acrylic moiety acting as alkylating moiety are reported, and structure-activity relationships detd. For example, indolecarboxylic acid I reacted with pyrrole deriv. II to give analog III (X = Y = CH, Z = NMe) in 63% yield. With respect to antiproliferative activity against L1210 and K562 cells, III (X = H, Y = CH, Z = NMe; X = CH, Y = H, Z = NMe) showed the greatest potency, while III (X = Y = CH, Z = NMe, O) exhibit the lowest activity. Among the synthesized compds. III (X = CH, Y = H, Z = NMe) was found to be the most potent member of this class and it is 70-fold more active than the bis-pyrrole counterpart against L1210 cell line. In addn., the cytotoxicity of derivs. III against KB cells and the influence of different glutathione (GSH) concns. on the cytotoxic effects was also investigated.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
