{"id":{"repo_id":"rgu","oai_identifier":"oai:rgu-repository.worktribe.com:2807437"},"canonical_url":"https://search.dev.ndltd.org/etd/rgu/oai:rgu-repository.worktribe.com:2807437","repository":{"repo_id":"rgu","name":"Robert Gordon University","base_url":"https://rgu-repository.worktribe.com/oaiprovider"},"display":{"title":"The synthesis of biologically active oxa-polyamine analogues, homologues and conjugates.","abstract":"Polyamines such as putrescine, spermidine, and spermine and their derivatives are found to be present in every living cell. Being products of amino acid metabolism polyamines play an important role in normal cell function and replication. Analogues, homologues, and derivatives of natural polyamines have been synthesised in order to evaluate the precise role of natural polyamines. In addition many synthesised polyamines have been shown to possess anti-cancer (bis-ethylspermine), anti-parasitic (bis-benzylspermine), and anti-HIV activities (cyclams). Recent studies have shown that oxa-polyamines such as 3-aminooxy-1-aminopropane (APA) and others form an interesting group of compounds exhibiting a number of biological activities. The presence of an oxygen atom next to a nitrogen atom dramatically changes the properties of polyamines. This is explained by the fact that an oxygen atom decreases the pKa value of the amine and hence helps the transport of oxa-amines through the cell membrane. Our major task was to develop synthetic methods for the synthesis of polyamine oxa-analogues and homologues, and also to evaluate their biological properties as potential anticancer and anti-parasitic agents. A literature review was conducted on the synthesis of polyamines and their derivatives and it was shown that not much work was reported on the synthesis and chemistry of oxa-polyamines. Therefore it was necessary to develop new synthetic methodologies for the synthesis of polyamines. New methodology for the synthesis of novel polyamine analogues and homologues developed and a number of oxa-polyamine analogues, homologues and derivatives synthesised. The reaction mechanisms of amine-oxyamine rearrangement were studied. These compounds were used as intermediates for the preparation of novel oxa-polyamines. The approach of using a variety of protecting groups has allowed ‘orthogonal’ protection (i.e. protecting groups can be removed one by one under different reaction conditions). It was shown that the current strategy we have developed, can be applied to the synthesis of different types of oxa-polyamines and hence allows ‘custom’ synthesis which is very useful for the evaluation of structure-activity relationships. Synthetic procedures were modified in order to increase yields of the products. Structures of all synthesised compounds were confirmed by IR spectrophotometry, NMR spectrometry and mass-spectral analyses. The chemistry developed to synthesise polyamine oxa-analogues, was used to prepare novel oxa-azamacrocycles bearing N-O moieties in the ring. A synthetic strategy was developed for the synthesis of oxa-azamacrocycles in high yields. Preliminary study into the complexing properties of novel oxa-azamacrocycles with metal ions was undertaken and it was shown that these macrocycles form complexes with Zn, Co and Ni ions where metal is co-ordinated to nitrogens. A selection of synthesised oxa-polyamine analogues and homologues was sent to The National Cancer Institute (USA) for screening of their anticancer activity. Most of the compounds showed low activity (IC50 ~ 10-100 mu M) against most cancer cell lines but some compounds were shown to posses higher activity (IC50 ~ 2-5 mu M). Relationship between chain length, structure of functional group and activity was established. Investigation into the activity of oxa-polyamine derivatives towards parasites T. cruzi was carried out at the Department of Biochemistry (University of Dundee) and some of the compounds were shown to inhibit the growth of the parasite at low concentration of drug IC50 ~2 mu M.","abstract_html":"Polyamines such as putrescine, spermidine, and spermine and their derivatives are found to be present in every living cell. Being products of amino acid metabolism polyamines play an important role in normal cell function and replication. Analogues, homologues, and derivatives of natural polyamines have been synthesised in order to evaluate the precise role of natural polyamines. In addition many synthesised polyamines have been shown to possess anti-cancer (bis-ethylspermine), anti-parasitic (bis-benzylspermine), and anti-HIV activities (cyclams). Recent studies have shown that oxa-polyamines such as 3-aminooxy-1-aminopropane (APA) and others form an interesting group of compounds exhibiting a number of biological activities. The presence of an oxygen atom next to a nitrogen atom dramatically changes the properties of polyamines. This is explained by the fact that an oxygen atom decreases the pKa value of the amine and hence helps the transport of oxa-amines through the cell membrane. Our major task was to develop synthetic methods for the synthesis of polyamine oxa-analogues and homologues, and also to evaluate their biological properties as potential anticancer and anti-parasitic agents. A literature review was conducted on the synthesis of polyamines and their derivatives and it was shown that not much work was reported on the synthesis and chemistry of oxa-polyamines. Therefore it was necessary to develop new synthetic methodologies for the synthesis of polyamines. New methodology for the synthesis of novel polyamine analogues and homologues developed and a number of oxa-polyamine analogues, homologues and derivatives synthesised. The reaction mechanisms of amine-oxyamine rearrangement were studied. These compounds were used as intermediates for the preparation of novel oxa-polyamines. The approach of using a variety of protecting groups has allowed ‘orthogonal’ protection (i.e. protecting groups can be removed one by one under different reaction conditions). It was shown that the current strategy we have developed, can be applied to the synthesis of different types of oxa-polyamines and hence allows ‘custom’ synthesis which is very useful for the evaluation of structure-activity relationships. Synthetic procedures were modified in order to increase yields of the products. Structures of all synthesised compounds were confirmed by IR spectrophotometry, NMR spectrometry and mass-spectral analyses. The chemistry developed to synthesise polyamine oxa-analogues, was used to prepare novel oxa-azamacrocycles bearing N-O moieties in the ring. A synthetic strategy was developed for the synthesis of oxa-azamacrocycles in high yields. Preliminary study into the complexing properties of novel oxa-azamacrocycles with metal ions was undertaken and it was shown that these macrocycles form complexes with Zn, Co and Ni ions where metal is co-ordinated to nitrogens. A selection of synthesised oxa-polyamine analogues and homologues was sent to The National Cancer Institute (USA) for screening of their anticancer activity. Most of the compounds showed low activity (IC50 ~ 10-100 mu M) against most cancer cell lines but some compounds were shown to posses higher activity (IC50 ~ 2-5 mu M). Relationship between chain length, structure of functional group and activity was established. Investigation into the activity of oxa-polyamine derivatives towards parasites T. cruzi was carried out at the Department of Biochemistry (University of Dundee) and some of the compounds were shown to inhibit the growth of the parasite at low concentration of drug IC50 ~2 mu M.","abstract_has_math":false,"creators":["Kuksa, Vladimir A."],"institution":"Robert Gordon University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["P. Kong, R. Buchan and M. 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Being products of amino acid metabolism polyamines play an important role in normal cell function and replication. Analogues, homologues, and derivatives of natural polyamines have been synthesised in order to evaluate the precise role of natural polyamines. In addition many synthesised polyamines have been shown to possess anti-cancer (bis-ethylspermine), anti-parasitic (bis-benzylspermine), and anti-HIV activities (cyclams). Recent studies have shown that oxa-polyamines such as 3-aminooxy-1-aminopropane (APA) and others form an interesting group of compounds exhibiting a number of biological activities. The presence of an oxygen atom next to a nitrogen atom dramatically changes the properties of polyamines. This is explained by the fact that an oxygen atom decreases the pKa value of the amine and hence helps the transport of oxa-amines through the cell membrane. Our major task was to develop synthetic methods for the synthesis of polyamine oxa-analogues and homologues, and also to evaluate their biological properties as potential anticancer and anti-parasitic agents. A literature review was conducted on the synthesis of polyamines and their derivatives and it was shown that not much work was reported on the synthesis and chemistry of oxa-polyamines. Therefore it was necessary to develop new synthetic methodologies for the synthesis of polyamines. New methodology for the synthesis of novel polyamine analogues and homologues developed and a number of oxa-polyamine analogues, homologues and derivatives synthesised. The reaction mechanisms of amine-oxyamine rearrangement were studied. These compounds were used as intermediates for the preparation of novel oxa-polyamines. The approach of using a variety of protecting groups has allowed ‘orthogonal’ protection (i.e. protecting groups can be removed one by one under different reaction conditions). It was shown that the current strategy we have developed, can be applied to the synthesis of different types of oxa-polyamines and hence allows ‘custom’ synthesis which is very useful for the evaluation of structure-activity relationships. Synthetic procedures were modified in order to increase yields of the products. Structures of all synthesised compounds were confirmed by IR spectrophotometry, NMR spectrometry and mass-spectral analyses. The chemistry developed to synthesise polyamine oxa-analogues, was used to prepare novel oxa-azamacrocycles bearing N-O moieties in the ring. A synthetic strategy was developed for the synthesis of oxa-azamacrocycles in high yields. Preliminary study into the complexing properties of novel oxa-azamacrocycles with metal ions was undertaken and it was shown that these macrocycles form complexes with Zn, Co and Ni ions where metal is co-ordinated to nitrogens. A selection of synthesised oxa-polyamine analogues and homologues was sent to The National Cancer Institute (USA) for screening of their anticancer activity. Most of the compounds showed low activity (IC50 ~ 10-100 mu M) against most cancer cell lines but some compounds were shown to posses higher activity (IC50 ~ 2-5 mu M). Relationship between chain length, structure of functional group and activity was established. Investigation into the activity of oxa-polyamine derivatives towards parasites T. cruzi was carried out at the Department of Biochemistry (University of Dundee) and some of the compounds were shown to inhibit the growth of the parasite at low concentration of drug IC50 ~2 mu M."]},{"key":"dc:title","label":"Title","values":["The synthesis of biologically active oxa-polyamine analogues, homologues and conjugates."]}]}],"canonical_facts":{"dc:contributor.advisor":["P. Kong, R. Buchan and M. Fraser"],"dc:contributor.sponsor":["RGU Internal Funding","New Funding Organisation"],"dc:creator":["Kuksa, Vladimir A."],"dc:date":["1999-02-28"],"dc:date.issued":["1999"],"dc:description.abstract":["Polyamines such as putrescine, spermidine, and spermine and their derivatives are found to be present in every living cell. Being products of amino acid metabolism polyamines play an important role in normal cell function and replication. Analogues, homologues, and derivatives of natural polyamines have been synthesised in order to evaluate the precise role of natural polyamines. In addition many synthesised polyamines have been shown to possess anti-cancer (bis-ethylspermine), anti-parasitic (bis-benzylspermine), and anti-HIV activities (cyclams). Recent studies have shown that oxa-polyamines such as 3-aminooxy-1-aminopropane (APA) and others form an interesting group of compounds exhibiting a number of biological activities. The presence of an oxygen atom next to a nitrogen atom dramatically changes the properties of polyamines. This is explained by the fact that an oxygen atom decreases the pKa value of the amine and hence helps the transport of oxa-amines through the cell membrane. Our major task was to develop synthetic methods for the synthesis of polyamine oxa-analogues and homologues, and also to evaluate their biological properties as potential anticancer and anti-parasitic agents. A literature review was conducted on the synthesis of polyamines and their derivatives and it was shown that not much work was reported on the synthesis and chemistry of oxa-polyamines. Therefore it was necessary to develop new synthetic methodologies for the synthesis of polyamines. New methodology for the synthesis of novel polyamine analogues and homologues developed and a number of oxa-polyamine analogues, homologues and derivatives synthesised. The reaction mechanisms of amine-oxyamine rearrangement were studied. These compounds were used as intermediates for the preparation of novel oxa-polyamines. The approach of using a variety of protecting groups has allowed ‘orthogonal’ protection (i.e. protecting groups can be removed one by one under different reaction conditions). It was shown that the current strategy we have developed, can be applied to the synthesis of different types of oxa-polyamines and hence allows ‘custom’ synthesis which is very useful for the evaluation of structure-activity relationships. Synthetic procedures were modified in order to increase yields of the products. Structures of all synthesised compounds were confirmed by IR spectrophotometry, NMR spectrometry and mass-spectral analyses. The chemistry developed to synthesise polyamine oxa-analogues, was used to prepare novel oxa-azamacrocycles bearing N-O moieties in the ring. A synthetic strategy was developed for the synthesis of oxa-azamacrocycles in high yields. Preliminary study into the complexing properties of novel oxa-azamacrocycles with metal ions was undertaken and it was shown that these macrocycles form complexes with Zn, Co and Ni ions where metal is co-ordinated to nitrogens. A selection of synthesised oxa-polyamine analogues and homologues was sent to The National Cancer Institute (USA) for screening of their anticancer activity. Most of the compounds showed low activity (IC50 ~ 10-100 mu M) against most cancer cell lines but some compounds were shown to posses higher activity (IC50 ~ 2-5 mu M). Relationship between chain length, structure of functional group and activity was established. Investigation into the activity of oxa-polyamine derivatives towards parasites T. cruzi was carried out at the Department of Biochemistry (University of Dundee) and some of the compounds were shown to inhibit the growth of the parasite at low concentration of drug IC50 ~2 mu M."],"dc:identifier":["oai:rgu-repository.worktribe.com:2807437","https://doi.org/10.48526/rgu-wt-2807437"],"dc:identifier.uri":["https://rgu-repository.worktribe.com/2807437/1/KUKSA%201999%20The%20synthesis%20of%20biologically%20active"],"dc:language":["en"],"dc:publisher.institution":["Robert Gordon University"],"dc:relation.isreferencedby":["https://rgu-repository.worktribe.com/output/2807437"],"dc:subject":["Polyamines","Cell biology","Oxygen","Nitrogen","Oxa-polyamines","Literature review","Spectrographical analysis","Oxa-azamacrocycles","Bis-ethylspermine","Bis-benzylspermine","Cyclams"],"dc:title":["The synthesis of biologically active oxa-polyamine analogues, homologues and conjugates."],"dc:type":["Thesis"]},"updated_at":"2026-07-24T04:10:09Z"}