Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action.

ABSTRACT: Phenanthriplatin (PtPPH) is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells. Although the aqua-activated drug has been assumed to be the precursor for DNA damage, it is still under debate whether the way in which that metallodrug attacks to DNA is dominated by a direct binding to a guanine base or rather by an intercalated intermediate product. Aiming to capture the mechanism of action of PtPPH, the present contribution used theoretical tools to systematically assess the sequence of all possible mechanisms on drug activation and reactivity, for example, hydrolysis, intercalation, and covalent damage to DNA. Ab initio quantum mechanical (QM) methods, hybrid QM/QM' schemes, and independent gradient model approaches are implemented in an unbiased

SUBMITTER: Veclani D 

PROVIDER: S-EPMC8479807 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature