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Synthesis, structure, and biological activity of ferrocenyl carbohydrate conjugates

TitleSynthesis, structure, and biological activity of ferrocenyl carbohydrate conjugates
Publication TypeJournal Article
Year of Publication2006
AuthorsFerreira, CL, Ewart, CB, Barta, CA, Little, S, Yardley, V, Martins, C, Polishchuk, E, Smith, PJ, Moss, JR, Merkel, M, Adam, MJ, Orvig, C
JournalInorganic Chemistry
Volume45
Pagination8414-8422
Date PublishedOct
Type of ArticleArticle
ISBN Number0020-1669
KeywordsACTIVITY IN-VITRO, AMINO-ACIDS, ANTIMALARIAL ACTIVITY, CHLOROQUINE COMPLEXES, DRUG-SENSITIVITY, ELECTROCHEMICAL STUDY/, METAL-BASED CHEMOTHERAPY, ORGANOMETALLIC ANALOG, PLASMODIUM-FALCIPARUM, TROPICAL DISEASES
Abstract

Seven ferrocenyl carbohydrate conjugates were synthesized. Coupling reactions of monosaccharide derivatives with ferrocene carbonyl chloride produced {6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-R-D-glucopyranoside)}1- ferrocene carboxamide (3), {1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1-ferrocene carboxylate (4), and {6O- (1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1-ferrocene carboxylate (5). Similarly, 1,1’-bis(carbonyl chloride)ferrocene was coupled with the appropriate sugars to produce the disubstituted analogues bis {6-N-(methyl 2,3,4-tri- O-acetyl-6-amino-6-deoxy-R-D-glucopyranoside)}- 1,1’-ferrocene carboxamide (8), bis {1-O-(2,3,4,6-tetra-O-benzyl-D- glucopyranose)}- 1,1’-ferrocene carboxylate (9), and bis {6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}- 1,1’-ferrocene carboxylate (10). {6-N-(Methyl-6-amino-6-deoxy-R-D-glucopyranoside)}-1-ferrocene carboxamide monohydrate (12) was synthesized via amide coupling of an activated ferrocenyl ester with the corresponding carbohydrate. All compounds were characterized by elemental analysis, H-1 NMR spectroscopy, and mass spectrometry. X-ray crystallography confirmed the solid-state structure of three ferrocenyl carbohydrate conjugates: 2-N-(1,3,4,6-tetra-O- acetyl-2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (1), 1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D- glucopyranose)-1-ferrocene carboxylate (2), and 12. The above compounds, along with bis {2-N- ( 1,3,4,6-tetra-O- acetyl-2-amino-2-deoxy-D-glucopyranose)}-1,1’-ferrocene carboxamide (6), bis {1- S- (2,3,4,6-tetra-O- acetyl-1-deoxy-1- thio-D-glucopyranose)}- 1,1’-ferrocene carboxylate (7), and 2-N-(2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (11) were examined for cytotoxicity in cell lines (L1210 and HTB-129) and for antimalarial activity in Plasmodium falciparum strains (D10, 3D7, and K1, a chloroquine- resistant strain). In general, the compounds were nontoxic in the human cell line tested (HTB-129), and compounds 4, 7, and 9 showed moderate antimalarial activity in one or more of the P. falciparum strains.

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