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Asian Journal of Biomedical and Pharmaceutical Sciences | ISSN: 2249-622X | Volume 8
October 22-23, 2018 | Frankfurt, Germany
&
Joint Event
Chemistry and Organic Chemistry
8th World Congress on
Biomedicine & Pharmacotherapy
International Conference on
The development of nucleoside and nucleotide analogs or
mimetics is a relevant approach in medicinal chemistry,
aiming at accessing molecules that may interfere with
biological processes in which natural nucleos(t)ides act
and are over-activated in diseases such as cancer or viral
infections. Among these events are nucleic acid replication,
the inhibition or the blocking of which conduces to
anticancer or to antiviral effects. In this context, some
synthetic nucleos(t)ides have reached clinical application.
Acquisition of resistance of cancer cells and some virus
towards nucleos(t)ides analogs is a major limitation of
their use as drugs. The ability of these types of molecules
to show antimicrobial effects and to inhibit cholinesterases
has also been described. Therefore, the development of
novel nucleos(t)ide-based structures that may exhibit new
mechanisms of action as well as the exploitation on rather
less studied potential therapeutic uses for these types of
compounds is highly encouraging. In this context, in this
communication the synthesis and the biological evaluation
of novel nucleosides constructed on 5/6-azido glycosyl units
and on D-glucuronamide templates, 5’/6’-isonucleosides and
nucleotideanalogs comprisingpotential neutral and relatively
stable bioisostere moieties for a phosphate system, namely
phosphoramidate, sulfonamide or phosphonate groups, is
presented. The synthetic strategies for their access included
N-glycosylation, sugar azidation, azide-alkyne 1,3-dipolar
cycloaddition, Mitsunobu coupling, Arbuzov or Staudinger-
type reactions as key steps. Some molecules revealed potent
antiproliferative effects in cancer cells or showed their
ability to inhibit cholinesterases. Their GI50 or Ki values
were similar or close to those of standard drugs, turning
them promising lead molecules for cancer or for Alzheimer’s
disease. Preliminary assays also indicated the potential
interest of some nucleosides as anti-flavivirus agents, due to
their propensity to inhibit or to destabilize an essential ATP-
dependent non-structural enzyme for Zika-virus replication.
Speaker Biography
Nuno M Xavier (b. Nov. 1982, Vila Real, Portugal) received a dual Ph.D. degree in Organic
Chemistry from the University of Lisbon and from the National Institute of Applied
Sciences of Lyon in 2011, where he devised new synthetic methodologies for novel
highly functionalized monosaccharide derivatives of antimicrobial potential. He worked
afterwards as Postdoctoral Researcher in the University of Natural Resources and Life
Sciences of Vienna in the synthesis of new potentially antibacterial heptose-based
compounds.HecarriedoutanotherpostdoctoralresearchperiodattheFacultyofSciences,
University of Lisbon and in 2014 he became Researcher (FCT Investigator) at this Institution.
His research activities, reported in more than 30 publications and frequently presented in
international conferences, are within the context of organic and medicinal chemistry and
focus on the development of new bioactive carbohydrate derivatives and nucleos(t)ide
analogs as inhibitors of relevant therapeutic targets or disease-associated biological events.
e:
Nuno Manuel Xavier
Universidade de Lisboa, Portugal
Synthesis and therapeutic potential of innovative nucleoside and nucleotide analogs
Nuno Manuel Xavier, Chemistry and Biomedicine 2018, Volume 8
DOI: 10.4066/2249-622X-C4-010