1,721,265 research outputs found
Anticancer agents:towards the future
No full textA major need in cancer chemotherapy is the availability of cancer cell-specific drugs. This paper discusses recent advances and perspectives in the field of selective drug recognition considering the key targets tyrosine kinases, DNA-topoisomerases and telomeras
Advances in DNA sequence specific agents
No full textIn this volume the entire focus is devoted to the macromolecule target specificity of DNA interactive developmental therapeutic agents of current interest. A brief introduction to DNA interactive anticancer agents is included for readers who may benefit from an overview surrounding the developments that have contributed to our general understanding of this field. The following nine chapters have been carefully chosen so that they describe topics which are at the forefront of development in DNA-targeted cancer chemotherapy. Issues that have been addressed include the mechanisms of selective DNA topoisomerase I and II poisoning by antitumor agents (Chapters 1 and 2), sequence-specific recognition of DNA by groove-binding drugs and drug-conjugates (Chapters 3 and 4), recent developments in nitrogen mustard alkylating agents and their potential use for antibody-directed enzyme-prodrug therapy (Chapter 5), nonclassical platinum anticancer complexes, including dinuclear and trans-platinum derivatives (Chapter 6), DNA cleaving antitumor chromoproteins containing reactive enediyne moieties, which exhibit interesting free-radical chemistry along with selective targeting (Chapter 7), the potential of new sequence-specific antisense and antigene therapy in oncology (Chapter 8), and finally the conceivable chemotherapeutic use of mimetics of the DNA structure, obtained by substitution of the sugar-phosphate natural chain with a peptide backbone, the so-called peptide nucleic acids (Chapter 9). Important approaches being currently investigated for selective cancer treatment, such as gene therapy and immunochemotherapy, are not discussed in this volume since they fall beyond its scope
Solid-state infrared absorption spectra and chain arrangement in some synthetic homooligopeptides in the intermolecularly hydrogen-bonded pleated-sheet beta-conformation.
No full textThe peculiar binding properties of 4'-deoxy,4'-iododoxorubicin to isolated DNA and 175 bp nucleosomes
No full textAntitumor potential of aza-bioisosterism in anthracenedione-based drugs
No full textAza-bioisosteres of anthracene-9,10-diones and of
anthrapyrazoles comprise an innovative class of anticancer compounds. They
are formally derived by introduction of one or more nitrogens into the
carbocyclic ring system of the parent drugs. Bioisosteres exhibit extensive
changes in the physico-chemical properties and in the interactions with the
pharmacological targets, DNA and DNA-topoisomerase II, when compared to
the carbocyclic analogues. A favourable spectrum of activity, reduced side
effects and a unique tropism for solid tumors make the new derivatives a very
interesting family of drugs. In particular, a 2-aza-anthracene-9,10-dione and a
9-aza-anthrapyrazole derivative are presently undergoing advanced clinical
trials and appear to be promising in view of their approval as anticancer drugs
In front of and behind the replication fork: bacterial type IIA topoisomerases
No full textTopoisomerases are vital enzymes specialized
in controlling DNA topology, in particular supercoiling and
decatenation, to properly handle nucleic acid packing and
cell dynamics. The type IIA enzymes act by cleaving both
strands of a double helix and having another strand from
the same or another molecule cross the DNA gate before a
re-sealing event completes the catalytic cycle. Here, we
will consider the two types of IIA prokaryotic topoisomerases,
DNA Gyrase and Topoisomerase IV, as crucial
regulators of bacterial cell cycle progression. Their synergistic
action allows control of chromosome packing and
grants occurrence of functional transcription and replication
processes. In addition to displaying a fascinating
molecular mechanism of action, which transduces chemical
energy into mechanical energy by means of large conformational
changes, these enzymes represent attractive
pharmacological targets for antibacterial chemotherapy
The quinolone family: from antibacterial to anticancer agents
No full textThe present review focuses on the structural modifications responsible for the transformation of an antibacterial
into an anticancer agent. Indeed, a distinctive feature of drugs based on the quinolone structure is their remarkable ability
to target different type II topoisomerase enzymes. In particular, some congeners of this drug family display high activity
not only against bacterial topoisomerases, but also against eukaryotic topoisomerases and are toxic to cultured mammalian
cells and in vivo tumor models. Hence, these cytotoxic quinolones represent an exploitable source of new anticancer
agents, which might also help addressing side-toxicity and resistance phenomena. Their ability to bind metal ion cofactors
represents an additional means of modulating their pharmacological response(s). Moreover, quinolones link
antibacterial and anticancer chemotherapy together and provide an opportunity to clarify drug mechanism across divergent
species
Alternative approaches to the discovery and development of telomerase-targeted anticancer drugs
No full textFour different approaches have been reviewed herein: i) nucleoside analogs as mock agents of the reverse transcriptase (hTERT) catalytic site; ii) miscellaneous molecules with unknown mechanism(s) of action; iii) inhibitors of upstream processes of regulation of the hTERT subunit; iiii) immunotherapy against immunogenic hTERT-derived peptides
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