title: Derivatives form better lipoxygenase inhibitors than piperine: in vitro and in silico study.
abstract: Piperine is a secondary metabolite of black pepper. Its uses in medicine were already studied. However, its derivatives have not gained considerable attention. In the presented study, the Lipoxygenase (LOX) inhibitory activity of piperine and its derivatives, piperonylic acid, piperic acid, and piperonal have been assessed and compared by enzyme kinetics, ITC and molecular modeling experiments. The presented investigations expressed that all the studied compounds inhibited LOX by binding at its active site. The IC(50) values of these compounds were deduced from the kinetics data and found to be 85.79, 43.065, 45.17, and 50.78 μm for piperine, piperonylic acid, piperic acid, and piperonal, respectively. The binding free energies obtained from ITC experiments were -7.47, -8.33, -8.09, and -7.86 kcal/mol for piperine, piperonylic acid, piperic acid, and piperonal, respectively. Similarly, the glide scores obtained for piperine, piperonylic acid, piperic acid, and piperonal were -7.28, -10.32, -10.72, and -9.57 kcal/mol, respectively. The results of ITC and molecular modeling experiments suggested that piperonylic acid and piperonal exhibit stronger binding at the active site than piperine does. From the presented studies, it could be concluded that derivatives of piperine may be of higher significance than piperine for certain medicinal applications, implicating (Ayurvedic) fermented herbal drugs with piperine in them.
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Muringayil J
authors.initials: MJ
authors.lastname: Tomy
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Chelankara S
authors.initials: CS
authors.lastname: Sharanya
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Kalarickal V
authors.initials: KV
authors.lastname: Dileep
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Shankar
authors.initials: S
authors.lastname: Prasanth
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Abudulhameed
authors.initials: A
authors.lastname: Sabu
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Chittalakkottu
authors.initials: C
authors.lastname: Sadasivan
authors.affiliation: Inter University Centre for Bioscience and Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India.
authors.forename: Madathilkovilakathu
authors.initials: M
authors.lastname: Haridas
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D003198:Computer Simulation; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008084:Lipoxygenase / Q000737:chemistry / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D029222:Piper nigrum / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013025:Glycine max / Q000201:enzymology
chemical_list: D000470:Alkaloids; D001547:Benzaldehydes; D001565:Benzoates; D052117:Benzodioxoles; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D008084:Lipoxygenase; C017637:piperic acid; C005454:piperonal; C005455:piperonylic acid; C008922:piperine
keywords: LOX; and ITC; piperine; piperonal; piperonylic acid