THE DESIGN, SYNTHESIS AND ANTI-TUMOUR PROPERTIES OF AURONE ANALOGUES AS PRKACA INHIBITORS

Vibina K., Dr. Shebina P. Rasheed*, Krishnendu P. R., Dr. Arun Rasheed and Neethu Varghese

ABSTRACT

The antiprostate cancer effect of Aurone analogues is revealed by inhibiting PRKACA in recent studies. PRKACA
is the catalytic subunit of cAMP-dependent protein kinase A's alpha catalytic subunit. Overexpression of PRKACA
induces severe cancer in prostate cells and plays a crucial role in cell signalling for numerous cellular activities.
The compounds which inhibit PRKACA can be developed as anti-prostate cancer agents. Molecular docking
studies were used to generate a panel of Aurone analogues, which were then synthesised by an oxidative
cyclization of 2'-Hydroxy chalcones and their structures validated using several spectrometric methods.
Commercially available 1'-Hydroxy-2'-acetonaphthones were used to make the chalocones. The compounds were
then put through a series of pharmacological tests, including the MTT assay (PC-3 cells) and the DPPH assay. All
the compounds show cytotoxic activity against PC-3 (prostate cancer cells). The results demonstrated that the
compounds AU-F(2-(4-Fluorobenzylidene) naphtho[1,2-b] furan-3(2H)-one) and AU-T(2- (Thiophen-2-
ylmethylene) naphtha [1,b]furan3 (2H)one) with IC50 values of 37.4461 μg/ml and 49.8939 μg/ml have shown
better activity than the standard, Bicalutamide(IC50-55.72μg/ml). And the compound AU-A((2-(4-
Methoxybenzylidene) naphtho[1,2-b]furan3(2H)one) exhibits moderate activity with an IC50 value of
65.8055μg/ml. and In addition, the molecular docking study by using PDB ID- 2GU8 revealed that the compound
AU-T(2-(Thiophen-2-ylmethylene) naphtha [1,b]furan3 (2H)one) have a high binding affinity for the PRKACA
subunit. Results of DPPH Assay shows that AU-F, AU-T and AU-A have better activity than standard Ascorbic
acid. The synthesized Aurone derivatives exhibit anti-cancer activity in different ratios. Among them the
compounds AU-F, AU-T and AU-A are worthy of further development as anti-prostate cancer agents.

Keywords: Aurones, Naphthofuranones, DPPH Assay, PRKACA inhibition, Prostate Cancer, PC-3, MTT Assay, 2’-Hydroxy chalcones.