Synthesis and biological evaluation of O-methyl and O-ethyl NSAID hydroxamic acids

Abstract

This paper reports the synthesis of O-methyl and O-ethyl NSAID hydroxamic acids, their antimicrobial activities, and their ability to inhibit urease and soybean lipoxygenase activities. Ibuprofen and fenoprofen hydroxamic acids with free hydroxy groups present the highest antimicrobial activity, while indomethacin and diclofenac analogs show significantly lower antimicrobial activity. Diclofenac hydroxamic acid 4e exerts the highest anti-urease activity. Indomethacin O-ethyl hydroxamic acid 3h and ibuprofen O-benzyl hydroxamic acid 4b exert significant inhibitory activities on soybean lipoxygenase. Fenoprofen and indomethacin O-ethyl hydroxamic acids 3b and 3h and diclofenac and indomethacin O-benzyl analogs 4g and 4i highly inhibit lipid peroxidation. The highest antioxidant activity was shown by fenoprofen derivative 3b.

Keywords::

• NSAID hydroxamic acids
• antimicrobial activity
• urease
• antioxidant activity
• soybean lipoxygenase
• inhibition

Acknowledgements

Support for this study by the Ministry of Science, Education and Sports of the Republic of Croatia (Project No. 006- 0000000-3216) as well as the National Employment and Development Agency (grant 14V09809) is gratefully acknowledged. The authors would like to thank Professor Tihana žanić-Grubišić for help with antiurease activity testing and Dr. C. Hansch and Biobyte Corp., 201 West 4th Str., Suite 204, Claremont, CA 91711, USA for free access to the C-QSAR program.

Declaration of interest: The authors report no conflicts of interest.