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Rationalization of the Superior Anticancer Activity of Phenanthriplatin: An In‐Depth Computational Exploration
Author(s) -
Dabbish Eslam,
Russo Nino,
Sicilia Emilia
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201903831
Subject(s) - guanine , cisplatin , bifunctional , chemistry , platinum , aquation , combinatorial chemistry , dna , chirality (physics) , intercalation (chemistry) , covalent bond , molecular dynamics , stereochemistry , anticancer drug , computational chemistry , drug , catalysis , biochemistry , organic chemistry , pharmacology , nucleotide , biology , genetics , kinetics , chiral symmetry breaking , quark , quantum mechanics , reaction rate constant , nambu–jona lasinio model , physics , chemotherapy , gene
In the effort to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents, a large number of cisplatin variants continues today to be prepared and tested. One of the applied strategies is to use monofunctional platinum complexes that, unlike traditional bifunctional compounds, are able to form only a single covalent bond with nuclear DNA. Chirality, aquation reaction, interaction with guanine and N ‐acetyl methionine as well as, intercalation into, binding to and distortion of DNA have been investigated by using both quantum mechanical DFT and molecular dynamics computations aiming at contributing to the elucidation of the molecular mechanism underlying the significantly enhanced spectrum of activity of the monofunctional Pt II drug phenanthriplatin. Analogous calculations have been performed in parallel for other two less potent monofunctional Pt II drugs, pyriplatin and enpyriplatin, which show very different cytotoxic effects.