Analysis of actinomycin D–DNA model complexes using a quantum-chemical criterion: Mulliken overlap populations

The nature of the chemical bond in oxyanionic crystals based on QTAIM topological analysis of electron densities

“…It was shown that for the same acceptor (O) of H-bonds between DNA and actinomycin, a greater overlap population corresponds to a shorter H/O distance. 98 It is interesting to nd out how electron density at BCP is related to other characteristics, such as Mulliken overlap populations, bond length and energy for H-bonds of oxyanionic crystals. As can be seen (Fig.…”

Antitumor compounds from actinomycetes: from gene clusters to new derivatives by combinatorial biosynthesis

“…Actinomycins are a family of bicyclic chromopeptide lactones with strong antineoplastic activity. 228,229 Actinomycin D 200, also known as dactinomycin, has mainly been used in the clinic for the treatment of pediatric solid tumors, since its approval in 1964. 3 It inhibits DNA-directed RNA synthesis by binding to doublestranded DNA, which prevents unwinding of the DNA to facilitate its interaction with RNA polymerase.…”

“…3 It inhibits DNA-directed RNA synthesis by binding to doublestranded DNA, which prevents unwinding of the DNA to facilitate its interaction with RNA polymerase. 228,229 The gene cluster directing actinomycin biosynthesis has been cloned from S. chrysomallus, and construction of hybrid NRPSs has been reported in order to obtain new peptide derivatives by swapping domains, which might in the future lead to the generation of new actinomycin derivatives. 230,231 It has been shown that synthetic derivatives of actinomycin D in which L-methylvaline is substituted with L-methylleucine show 100-fold improvement in antitumor activity, and inhibited the proliferation of and induced apoptosis in the human gastric carcinoma cell line SGC-7901, probably by inducing loss of mitochondrial potential and by decreasing bcl-2 gene expression.…”

Spectroelectrochemistry of the redox activation of anti-cancer drug mitoxantrone

“…However, it was shown that N-substitution for the amino-anthraquinone drugs may lead to a decrease of the electron affinity and electronegativity, that can result in reduced competition with oxygen for an electron in the mitochondrial electron transport chain, and therefore can influence the cardiotoxicity of the drug [25,26]. On another side, our previous studies on several anticancer drugs-DNA interaction (based on a quantum-chemical approach: Mulliken overlap population) have pointed out the importance of the ring substituents in the stabilization of the drug-DNA complexes, by an enhanced contribution of specific hydrogen bonding and other atom-atom intermolecular interactions [27,28]. For these reasons we have considered that quantum solvent-dependent calculations on the whole molecule, including conformational analysis, could bring useful information in the study of the cardiotoxicity of the anti-cancer drugs.…”