Modulation of Ornithine Decarboxylase Activity by Phenolics Based Structurally Related Compounds Synthesized on Steroidal and Non-Steroidal Skeleton and their Radical Scavenging Action

Abstract

In the present investigation, several phenolics based structurally related compounds of steroidal and nonsteroidal skeletons were synthesized and tested for their modulatory effect on ornithine decarboxylase (ODC) activity, an enzyme overexpressed in cancer. Additionally, these compounds were also examined for radical scavenging action to establish a correlation with the cancer chemopreventive property. Our result suggests that the tested compounds possessed radical scavenging activity, for being the inherent property of the phenolics. 3-(3’,4’5’-trimethoxyphenyl)-4,5,6- trimethoxyindan-1-one oxime (15) exhibited highest inhibition of enzyme activity (91%) followed by 1-(2,4- dibromophenyl)-3-[3-methoxyestra 1,3,5(10)-trien-17-acetate,2-yl]-2-propen-1-one (26) (85%), 2-Hydroxy, 3-(3’,4’,5’- trimethoxy phenyl)-4,5,6-trimethoxy ind-2-en-1-one (17) (80%), 1-(3,4-methylenedioxyphenyl)-3-(3,4,5- trimethoxyphenyl)-2-propen-1-one (13) (74%) and 1-(3-methoxy, 4-hydroxyphenyl)-3-[3-methoxyestra 1,3,5(10)-trien- 17-acetate, 2-yl]-2-propen-1-one (28)(67%). Furthermore, it was observed that 1-(3-Methoxy, 4- hydroxyphenyl)-3-[3- methoxyestra 1,3,5 (10)-trien-17-acetate, 2-yl]-2-propen-1-one (28) showed the highest scavenging effect (67%) in nitric oxide (NO) assay, whereas 1-(3-methylphenyl)-3-[3-methoxy, 17-hydroxyestra 1,3,5(10)-trien, 2-yl]-2-propen-1-one (25) showed maximum inhibition of radical formation in 2,2-diphenyl-1-picrylhydrazyl (DPPH) analysis. Most of these compounds possessed a 3,4,5- trimethoxyphenyl unit which might be inducing enzyme inhibition and scavenging radical formation which could be further investigated to establish the structure-activity relationship. Keywords: Phenolics, ornithine decarboxylase, NO, DPPH, steroidal, non-steroidal, chemopreventive property, carcinogenesis, cytotoxic, Sigma-Aldrich