IN SILICO MOLECULAR DOCKING STUDIES OF LICHEN METABOLITES AGAINST VARIOUS CANCER PROTEINS

Article history The architecture of lichen compounds offers a large area for developing scaffolds for combinatorial libraries towards discovery of lead compounds. The present study emphasizes the significance of lichen metabolites namely the depsides, depsidones and dibenzofuran derivatives well known for their anti-proliferative and cytotoxic activities. In this regard, molecular docking simulations were carried out for the lichen metabolites likely atranorin, lecanoric acid, salazinic acid & dibenzofuran derivatives (usnic acid) with various cancer proteins like, JNK1, MMP-9, Caspase-3, PARP-1, ERK2, AIF, FGFR2, AKT1, CDK2, CDK6 & PI3K, and the docked results were compared with the standard reference ligands (methotrexate & 5-fluorouracil). Among all the docked ligands, the depside - atranorin has shown satisfactory H-bond interactions with JNK1, MMP-9, CDK2, CDK6 & PI3K proteins and with highest glide score -9.83, -8.98, -10.25, -7.84 & -10.16, respectively; lecanoric acid has shown acceptable H-bond interactions with PARP-1, ERK2, CDK2 & CDK6 proteins with glide score -9.29, -8.28, -9.64, -7.53, respectively. The depsidone molecule salazinic acid has shown meaningful hydrogen bond interactions and binding energy with Caspase-3, AIF, FGFR2 & AKT1 and with glide score -7.71, -8.49, -11.26, -6.04, respectively. Of the dibenzofuran derivatives, usnic acid has shown adequate docking score with all the target proteins but amongst all the S1-S7 ligands, S3 & S4 have shown favorable H-bond interactions with the target cancer proteins. These docking results reveal that the lichen metabolites might have inhibitory activity against several cancer proteins, and are expected to be useful in conducting in vitro studies on the target specified cancer proteins and for further structural elucidation of lichen metabolites in the development of effective potent newer chemical entities with anti-cancer properties.