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Cuminaldehyde as a Lipoxygenase Inhibitor: In Vitro and In Silico Validation

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Abstract

The search for lipoxygenase (LOX) inhibitors has been carried out for decades due to its importance in inflammatory diseases. In the present study, it was observed that the methanolic extract of Cuminum cyminum L. inhibited LOX activity. Activity-guided screening of the C. cyminum crude extracts helped the identification and isolation of cuminaldehyde as a 15-LOX inhibitor. The enzyme kinetics analysis suggested cuminaldehyde to be a competitive inhibitor and the IC 50 value derived from LB plots is 1,370 μM. Binding constants of cuminaldehyde on LOX was deduced by isothermal titration calorimetry. The combined thermodynamics and molecular modeling analyses suggested cuminaldehyde as a competitive LOX inhibitor. It is proposed from the present study that the coordinate bond between the Fe2+ atom in the active site of the enzyme and the cuminaldehyde may be responsible for the enzyme inhibition. The study suggests that cuminaldehyde may be acting as an anti-inflammatory compound and may be therefore included in the category of leads for developing dual COX-LOX inhibitors as non-steroidal anti-inflammatory drugs (NSAIDs).

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Acknowledgments

The authors acknowledge Bioinformatics Infrastructure Facility (supported by DBT, Government of India) at the Department of Biotechnology and Microbiology, Kannur University for computational facilities. The authors also acknowledge Dr. S. Sudarslal and the mass spectrometry facility at the Amrita School of Biotechnology, supported under the research sponsoring agreement between Agilent Technologies Inc. and Amrita Vishwa Vidyapeetham, for the ESI-MS data acquisition and analysis. KVD thanks ICMR for the Senior Research Fellowship.

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Correspondence to M. Haridas.

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M. J. Tomy and K. V. Dileep contributed equally

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Tomy, M.J., Dileep, K.V., Prasanth, S. et al. Cuminaldehyde as a Lipoxygenase Inhibitor: In Vitro and In Silico Validation. Appl Biochem Biotechnol 174, 388–397 (2014). https://doi.org/10.1007/s12010-014-1066-0

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  • DOI: https://doi.org/10.1007/s12010-014-1066-0

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