In Silico Evaluation of Novel 3-Piperoylindole Compounds Synthesized from Piperine (Piper Nigrum Linn.) for Potential Anti-Cancer

The development of drugs that inhibit EGFR tyrosine kinase (EGFR-TK) is necessary to improve the effectiveness and durability of cancer treatment. In silico study employed a molecular docking approach to simulate the interaction between 3-piperoylindole (3-PI), a novel semi-synthetic derivative of piperine (Piper nigrum Linn.), and EGFR-TK. Redocking between the receptor and the original ligand yielded an RMSD value of 1.382 Å. The yield of the 3-PI compound was 37% w/w from piperoic acid. The docking results revealed that 3-PI (−8.7 kcal/mol) had a higher binding affinity than erlotinib (−7.7 kcal/mol) toward EGFR-TK. The binding affinity of 3-PI toward EGFR-TK was attributed to hydrophobic interactions and hydrogen bonds. These findings highlight the potential of this compound as anti-cancer for further in vitro and in vivo evaluation. HIGHLIGHTS 3-piperoylindole (3-PI) was synthesized from piperine (Piper nigrum) via a pre-target compound (piperoyl chloride) mechanism. 3-PI compound was obtained 37% w/w of yield from piperoic acid. The binding energy of the 3-PI compound evaluated using molecular docking approach showed −8.7 kcal/mol, which had a higher binding affinity than erlotinib (−7.7 kcal/mol) toward EGFR-TK. The binding affinity of 3-PI toward EGFR-TK was attributed to hydrophobic interactions and hydrogen bonds. These findings highlight the potential of this compound as anti-cancer for further in vitro and in vivo GRAPHICAL ABSTRACT