Molecular docking, ADMET profiling of gallic acid and its derivatives (N-alkyl gallamide) as apoptosis agent of breast cancer MCF-7 Cells

Abstract

Background In 2020, breast cancer has become the most common cancer in the world and in Indonesia. Searching for anticancer drugs using computational methods is considered more effective and selective than other methods. Gallic acid and its derivatives (esters and amides) are compounds that have biological activities such as anticancer effects. The aim of this study was to perform in-silico and in-vitro analysis of gallic acid derivatives (N-alkyl gallamide) as apoptosis agents for MCF7 breast cancer cells. Methods Target proteins were selected by analysis of protein-protein and drug-protein interactions. Molecular modelling was done by molecular docking. Predictive analysis of the ADMET profile of gallic acid and its derivatives (N-alkyl gallamide) was conducted using Marvin Sketch, Swissadme, protox II, and pkCSM pharmacokinetics. The selected target proteins were JUN, AKT1, CASP3, and CASP7. The MTT method was used to assess the three best compounds for their cytotoxic activity against MCF7 cells, while annexin V-FITC/PI and flow cytometry were used to analyze apoptosis. These tests were based on in-silico research. Results Compounds N-octyl gallamide, N-ters-butyl gallamide, and N-isoamyl gallamide were the three best gallic acid derivatives based on molecular modelling analysis of target proteins associated with breast cancer. The ADMET profile of the N-alkyl gallamide compound is predictable and shows a good profile as a candidate for anticancer drugs. The cytotoxic activity of the three compounds was expressed by their IC50 values of 205.2 ± 0.44 μM, 372.6 ± 4.09 μM, and 441.7 ± 1.41 μM, respectively. The apoptosis activity reaches 55 to 56% compared to control cells. Conclusion N-octyl gallamide, N-ters-butyl gallamide, and N-isoamyl gallamide have potential as an apoptosis agent of breast cancer MCF-7 Cells