FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2737396380> ?p ?o ?g. }

• W2737396380 abstract "Natural products originate from the enzyme-catalysed transformation of common intermediates through one or more biosynthetic pathways. Two such biosynthetic pathways, the mevalonate and the recently discovered deoxyxylulose phosphate pathways give rise to isoprenoid natural products. Isoprenoid natural products are biosynthesised from isoprene (C5) units, with incorporation of fragments from other biosynthetic pathways affording structural diversity. The teak wood derived natural product, tecomaquinone I (2.53), was identified as a potent inhibitor of human FTase, exhibiting activity in the nanomolar range. The structurally-related cytotoxic natural product, tectol (2.55) exhibited moderate inhibitory activity against FTase and P. falciparum. Analogues of tecomaquinone I (2.53), altering the isoprenoid fragment, were synthesised and their bioactivity examined. Increasing the number of isoprene units on the side chain afforded 4-methylpent-3-enyl (2.71 A???D) and 4,8-dimethylnona-3,7-dien-1-yl (2.78 A???D) analogues, both of which were synthesised as four (racemic) diastereomers. The analogues were not as potent as 2.53 in the FTase inhibition assays, with the 4-methylpent-3-enyl tecomaquinone analogues (2.71 A???D) exhibiting the highest activity. Anti-plasmodial assays revealed a specific structural requirement, with only analogues of tectol (2.55) exhibiting activity. Marine meroterpenoids, thiaplidiaquinones A (3.1) and B (3.2) were shown to induce apoptosis in Jurkat cells. Analogues of thiaplidiaquinones A (3.1) and B (3.2) and their regioisomers 3.3 and 3.4, altering the isoprenoid fragments, were synthesised biomimetically. Varying the number of isoprene units afforded prenyl and farnesyl analogues. The prenyl analogues (3.33???3.36) exhibited a similar profile to 3.1???3.4, where the regioisomers were more active than the natural products, in the anti-plasmodial, cytotoxicity and FTase inhibition assays while no trends were observed for the farnesyl analogues (3.47???3.50). The sesquiterpenoid, onchidal (4.40) was isolated from the defensive secretion of a shell-less mollusc. The feeding deterrent activity exhibited by the mollusc has been associated with the reactive fragments of 4.40. Analogues, bearing the enol acetate and dialdehyde forms of the reactive warhead of onchidal (4.40) were synthesised. n-Hexyl (4.61???4.63), cyclohexylethyl (4.71???4.73) and hexyne (4.88 and 4.89) analogues were synthesised and reactivity studies conducted with model thiol and amine nucleophiles. All the analogues exhibited selectivity towards amine nucleophiles forming diaminated pyrrole adducts. Reactivity studies conducted on lysozyme, examined by ESIMS and SDS-PAGE, detected modifications consistent with pyrrole adducts as well as evidence of protein crosslinking. Model reactions incorporating fluorescent tags on the hexyne analogue were achieved with dansyl and lissamine rhodamine azides through a ???click??? reaction." @default.
• W2737396380 created "2017-07-31" @default.
• W2737396380 creator A5009816451 @default.
• W2737396380 date "2016-01-01" @default.
• W2737396380 modified "2023-09-27" @default.
• W2737396380 title "Study of Bioactive Isoprenoid Natural Products" @default.
• W2737396380 hasPublicationYear "2016" @default.
• W2737396380 type Work @default.
• W2737396380 sameAs 2737396380 @default.
• W2737396380 citedByCount "0" @default.
• W2737396380 crossrefType "dissertation" @default.
• W2737396380 hasAuthorship W2737396380A5009816451 @default.
• W2737396380 hasConcept C15920480 @default.
• W2737396380 hasConcept C178790620 @default.
• W2737396380 hasConcept C181199279 @default.
• W2737396380 hasConcept C185592680 @default.
• W2737396380 hasConcept C206103511 @default.
• W2737396380 hasConcept C2779396153 @default.
• W2737396380 hasConcept C2779982574 @default.
• W2737396380 hasConcept C2780959689 @default.
• W2737396380 hasConcept C521977710 @default.
• W2737396380 hasConcept C553450214 @default.
• W2737396380 hasConcept C55493867 @default.
• W2737396380 hasConcept C57790582 @default.
• W2737396380 hasConcept C71240020 @default.
• W2737396380 hasConceptScore W2737396380C15920480 @default.
• W2737396380 hasConceptScore W2737396380C178790620 @default.
• W2737396380 hasConceptScore W2737396380C181199279 @default.
• W2737396380 hasConceptScore W2737396380C185592680 @default.
• W2737396380 hasConceptScore W2737396380C206103511 @default.
• W2737396380 hasConceptScore W2737396380C2779396153 @default.
• W2737396380 hasConceptScore W2737396380C2779982574 @default.
• W2737396380 hasConceptScore W2737396380C2780959689 @default.
• W2737396380 hasConceptScore W2737396380C521977710 @default.
• W2737396380 hasConceptScore W2737396380C553450214 @default.
• W2737396380 hasConceptScore W2737396380C55493867 @default.
• W2737396380 hasConceptScore W2737396380C57790582 @default.
• W2737396380 hasConceptScore W2737396380C71240020 @default.
• W2737396380 hasLocation W27373963801 @default.
• W2737396380 hasOpenAccess W2737396380 @default.
• W2737396380 hasPrimaryLocation W27373963801 @default.
• W2737396380 hasRelatedWork W1593995457 @default.
• W2737396380 hasRelatedWork W1967464496 @default.
• W2737396380 hasRelatedWork W1990850734 @default.
• W2737396380 hasRelatedWork W1999259520 @default.
• W2737396380 hasRelatedWork W2006807305 @default.
• W2737396380 hasRelatedWork W2023665888 @default.
• W2737396380 hasRelatedWork W2062830295 @default.
• W2737396380 hasRelatedWork W2112479566 @default.
• W2737396380 hasRelatedWork W2158353226 @default.
• W2737396380 hasRelatedWork W2179480115 @default.
• W2737396380 hasRelatedWork W2179990755 @default.
• W2737396380 hasRelatedWork W2521133164 @default.
• W2737396380 hasRelatedWork W2805688737 @default.
• W2737396380 hasRelatedWork W2949395279 @default.
• W2737396380 hasRelatedWork W2950086863 @default.
• W2737396380 hasRelatedWork W2952532946 @default.
• W2737396380 hasRelatedWork W2952828642 @default.
• W2737396380 hasRelatedWork W3106429176 @default.
• W2737396380 hasRelatedWork W773806999 @default.
• W2737396380 hasRelatedWork W833307864 @default.
• W2737396380 isParatext "false" @default.
• W2737396380 isRetracted "false" @default.
• W2737396380 magId "2737396380" @default.
• W2737396380 workType "dissertation" @default.