DOI: https://doi.org/10.24959/ophcj.13.754

The structure and biological properties of (4-hydroxy-1-methyl-2-oxo-1,2-dihydro-quinolin-3-yl)acetic acid and its esters

I. V. Ukrainets, O. V. Mospanova, T. V. Alexeeva

Abstract


Continuing the search of new effective and safe means for pain relief in the range of different derivatives of 4-hydroxyquinoline-2-ones (4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)acetic acid and series of its alkyl esters have been involved in the objects of our research. All pharmacological experiments in studying the anti-inflammatory and analgesic activity of the compounds synthesized have been carried out in white mice using standard screening models – «carrageenan edema» and «acetic acid writhing», respectively. Compounds that are not inferior to the anti-exudative and analgesic action of the known non-steroidal anti-inflammatory drug Diclofenac have been identified. In addition, the important structural and biological regularities, which are of interest for further research as a starting basis have been found. With the help of X-ray analysis the peculiarities of the spatial structure of some products synthesized have been studied. A detailed comparative analysis of X-ray diffraction data of the most active analgesics identified among the tested substances – methyl (4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl) acetate and its ethyl analogue has been performed. It is instrumentally confirmed that these two compounds have a substantially identical spatial structure, the same type of the intermolecular hydrogen bonds system and the same crystalline packing. However, they exhibit an analgesic effect approximately of the same level, but vary greatly in intensity of their anti-inflammatory properties. According to the results of the comprehensive analytical and biological studies the conclusion has been made that for all its undoubted importance the crystalline structure of substances is not the only factor that has a significant impact on their pharmacological properties.


Keywords


4-hydroxy-2-oxo-1,2-dihydroquinolines; hetarylacetic acids; complex esters; X-ray diffraction analysis; anti-inflammatory action; analgesic activity

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