Novel bivalent securinine mimetics as topoisomerase I inhibitors

Topoisomerase I Inhibitors.

Topoisomerase I inhibitors are a new class of anticancer agents with a mechanism of action aimed at interrupting DNA replication in cancer cells, the result of which is cell death. Most if not all Topoisomerase I inhibitors are derivatives of the plant extract camptothecin. Irinotecan (CPT-11), a semi-synthetic derivative of camptothecin, is approved in the United States for the treatment of co...

Novel and specific inhibitors of a poxvirus type I topoisomerase.

Vaccinia DNA topoisomerase (vTopo) is a prototypic pox virus family topoisomerase that shares extensive structural and mechanistic properties with the human type IB enzyme (hTopo) and is important for viral replication. Despite their far-reaching similarities, vTopo and hTopo have surprisingly distinct pharmacological properties. To further exploit these differences, we have developed recently ...

1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.

Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position...

BET-inhibitors as sensitizers for BH3-mimetics

Mutagenic activity of topoisomerase I inhibitors

Topoisomerase I-directed agents are now in Phase I and II clinical trials and show great promise as potentially important agents for cancer chemotherapy. Because of their mechanism of action they may also be potential mutagens; however, their mutagenicity and oncogenicity still remain to be elucidated. We have previously shown that VP-16, a topoisomerase II-directed agent, induces sister chroma...