IN SILICO ANALYSIS OF FUNCTIONAL SNPs OF ALOX12 GENE AND IDENTIFICATION OF PHARMACOLOGICALLY SIGNIFICANT FLAVONOIDS AS LIPOXYGENASE INHIBITORS

Abstract

Cancer is a disease affecting any part of the body and in comparison with normal cells there is an elevated level of lipoxygenase enzyme in different cancer cells. Thus generation of lipoxygenase enzyme inhibitors have suggested being valuable. Individual variation was identified by the functional effects of Single Nucleotide Polymorphisms (SNPs). 696 SNPs were identified from the ALOX12 gene, out of which 73 were in the coding non-synonymous region, from which 8 were found to be damaging. In silico analysis was performed to determine naturally occurring flavonoids such as isoflavones having the basic 3- phenylchromen-4-one skeleton for the pharmacological activity, like Genistein, Diadzein, Irilone, Orobol and Pseudobaptigenin. O-methylated isoflavones such as Biochanin, Calycosin, Formononetin, Glycitein, Irigenin, 5-O-Methylgenistein, Pratensein, Prunetin,$\psi$-Tectorigenin, Retusin and Tectorigenine were also used for the study. Other natural products like Aesculetin, a coumarin derivative; flavones such as ajoene and baicalein were also used for the comparative study of these natural compounds along with acteoside and nordihydroguaiaretic acid (antioxidants) and active inhibitors like Diethylcarbamazine, Zileuton and Azelastine as standard for the computational analysis. The protein-ligand interaction was studied and the docking analysis was performed by Patch Dock server using the 3D3L human arachidonate 12-lipoxygenase protein. Out of the 19 herbal constituents selected, it was found that Diadzein, Biochanin, Glycitein, Irigenin, 5-O-Methylgenistein, $\psi$-Tectorigenin and Tectorigenin showed significant binding affinity in inhibiting lipooxygenase enzyme as compared with standard compounds of acteoside, nordihydroguaiaretic acid, Diethylcarbamazine, Zileuton and azelastine. Naturally occurring compounds on further advancement could act as potent lipoxygenase inhibitors.