Ricerc@Sapienza

Background: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer.

We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation.

Microtubules are an attractive target for the development of active anti-leukemia agents (1). Despite some evidence, the therapeutic potential of colchicine site binding agents in chronic myeloid leukemia (CML) has not been adequately explored.
Recently, starting from previously reported aroylindoles (ARIs, e.g. 1) we have developed 3-aroyl-1-arylpyrroles (ARAPs, e.g. 2) via benzocracking approach (Chart 1) (2). Pursuing our studies, we designed and synthesized 3-aroyl-1,4-diarylpyrroles (ARDAPs, 3-16) as potential anticancer agents (3).