SYNTHESIS AND BIOLOGICAL EVALUATION OF MONOINDOLYL AND INDOLOCARBAZOLYL OXAZOLONES AND IMIDAZOLONES

Eight compounds structurally related to protein kinase C inhibitor MDL 27032 and substituted with indole moieties were synthesized. Their ac tivities towards protein kinase C (PKC) and protein kinase A (PKA) wer e determined. Their effect on PKC-mediated contraction of rat tracheal smooth muscle, their antiproliferative activity on two murine tumor c ell lines, melanoma B16 and leukemia P388 and their antimicrobial acti vity on a gram-positive bacterium Bacillus cereus were also examined. The mammalian and bacterial cell antiproliferative activity, as well a s vasorelaxant effect, observed for some of them could not be correlat ed to PKC or PKA inhibition. Only bulky bis-indolyl compounds exhibite d biological activity in these experiments. Rigid indolocarbazoles had the strongest antiproliferative activity.