title: Molecular modeling of DNA cross-linking analogues based on the azinomycin scaffold.
abstract: In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computational methods the Stochastic Dynamics with Energy Minimization (SDEM) approach yielded results superior to the others with the natural compound (r(2) > 0.9) and was adopted for studying other DNA adducts, obtaining good correlation between the average theoretical cross-linking properties and the antitumor activity scale. As a result, some interesting SAR considerations have been highlighted and a cross-linking conformation different from that of the azinomycin was identified in a less potent, simplified analogue.
authors.affiliation: Dipartimento di Scienze Farmacobiologiche, Università Magna Graecia di Catanzaro, I-88021 Roccelletta di Borgia, Catanzaro, Italy. alcaro@unicz.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Robert S
authors.initials: RS
authors.lastname: Coleman
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006020:Glycopeptides; D036341:Intercellular Signaling Peptides and Proteins; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry; D010455:Peptides
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D006020:Glycopeptides; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; C051055:azinomycin B; D004247:DNA