Hyaluronic acid based hydroxamate and conjugates with biologically active amines: In vitro effect on matrix metalloproteinase-2

• Published in: Carbohydrate polymers 2016-06, Vol.144, p.17-24
• Main Authors: Ponedel’kina, Irina Yu, Gaskarova, Aigul R., Khaybrakhmanova, Elvira A., Lukina, Elena S., Odinokov, Victor N.
• Format: Article
• Language: English
• Subjects: Amines - chemical synthesis; Amines - chemistry; Aniline Compounds - chemical synthesis; Aniline Compounds - chemistry; Conjugates; Humans; Hyaluronic acid; Hyaluronic Acid - chemical synthesis; Hyaluronic Acid - chemistry; Hydroxamate; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - chemistry; Matrix Metalloproteinase 2 - chemistry; Matrix metalloproteinase inhibitors; Matrix Metalloproteinase Inhibitors - chemical synthesis; Matrix Metalloproteinase Inhibitors - chemistry; Procaine - chemical synthesis; Procaine - chemistry; Recombinant Proteins - chemistry; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Triazoles - chemistry
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2016.02.022

•Hyaluronic acid (HA) hydroxamate was synthesized via O-hyaluronylisoureas.•HA conjugates with amines and hydrazides were obtained by carbodiimide technique.•HA derivatives were tested as matrix metalloproteinase-2 inhibitors (MMPIs).•The most efficient MMPIs were found to be HA conjugates with o-aminophenol and 4-aminoantipyrine.•HA hydroxamate showed only 40–50% inhibitory effect. In this study, water soluble hyaluronic acid (HA) based hydroxamate and conjugates with biologically active amines and hydrazides such as p- and o-aminophenols, anthranilic, 4- and 5-aminosalicylic acids, nicotinic, N-benzylnicotinic and isonicotinic hydrazides, p-aminobenzenesulfonamide (Streptocide), p-aminobenzoic acid diethylaminoethyl ester (Procaine), and 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (4-aminoantipyrene) were examined as matrix metalloproteinase-2 inhibitors (MMPIs). In a dose of 0.27–270μM, the most efficient MMPIs were HA conjugates with o-aminophenol=4-aminoantipyrine>4-aminosalicylic acid>5-aminosalicylic acid. Conjugates with Streptocide, Procaine and HA hydroxamate showed 40–50% inhibitory effect at all used concentrations. Conjugates with anthranilic acid and isonicotinic hydrazide (Isoniazid) in a dose of 0.27μM inhibited enzyme activity by ∼70%, but with the concentration increase their inhibitory effect was decreased.