Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

Abstract

SummaryWe present the synthesis and selected physicochemical properties of several novel symmetrical and unsymmetrical α,ω-nucleobase mono- and bis-amide conjugated systems containing aliphatic, aromatic or saccharidic linkages. The final stage of the synthesis involves condensation of a subunit bearing carboxylic group with an amine subunit. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) was found to be a particularly effective condensing agent. The subunits containing carboxylic groups were obtained by acidic hydrolysis of N-1 Michael adducts of uracils or N-9 Michael adducts of 6-chloropurine with methyl acrylate. The amines used were aliphatic/aromatic diamines, adenine, 5-substituted 1-(ω-aminoalkyl)uracils and 5′-amino-2′,5′-dideoxythymidine. The title compounds may find application as antiprotozoal agents. Moreover, preliminary microscopy TEM studies of supramolecular behaviour showed that target molecules with bolaamphiphilic structures were capable of forming highly ordered assemblies, mainly nanofibres.

Anticancer Activity of Chitosan, Chitosan Derivatives, and Their Mechanism of Action

“…Conjugation of nucleobase with various natural and synthetic biopolymers can form the derivatives with enhanced biological activity. For instance, phenanthridinium–nucleobase conjugates [158], metallocene–nucleobase conjugates [159], symmetrical and unsymmetrical, ω -nucleobase mono- and bis-amide conjugates [160], cyclodextrin–DNA conjugate [161], ferrocene–bis(nucleobase) conjugates [162, 163], neamine–nucleoside conjugates [164], DNA-peptide conjugates [165], peptide–nucleobase conjugates, and nucleobase PNA conjugates [166] have been found to inhibit a specific DNA or mRNA molecular expression as a result of an induced blockade in the transfer of genetic information from DNA to protein. Chitosan–nucleobase conjugate is an analogue of natural nucleobases and its anticancer mechanism is associated with its incorporation into the nuclear DNA during DNA synthesis and into mRNA during transcription.…”

A new chitosan–thymine conjugate: Synthesis, characterization and biological activity

“…Phenanthridinium-nucleobase conjugates [1], metallocene-nucleobase conjugates [2], symmetrical and unsymmetrical ˛,ω-nucleobase mono-& bis-amide conjugates [3], cyclodextrin-DNA conjugate [4], ferrocene-bis(nucleobase) conjugates [5], neamine-nucleoside conjugates [6], DNA-peptide conjugates [7], peptide-nucleobase conjugates, nucleobase PNA conjugates [8] are few examples that can inhibit the expression a specific DNA or mRNA molecule, inducing a blockade in the transfer of genetic information from DNA to protein either by antigene or antisense strategy. Single stranded domains of DNA and RNA play an essential role in a number of processes in living cells including those involving viruses.…”