In Silico Comparison of Quantum and Bioactivity Parameters of a Series of Natural Diphenyl Acetone Analogues, and In Vitro Caco-2 Studies on Three Main Chalcone Derivatives

This paper aims to compare the in silico and in vitro properties of a series of diphenyl acetone derivatives, specifically six chalcone analogues, namely benzophenone, chalcone, phloretin, phloridzin, nothofagin and 4-methylchalcone. The in silico studies were conducted using the Spartan’14 mechanistic program to perform a comparative analysis of the molecular, quantum and bioactivity parameters of the six analogues under study. The in vitro MTS studies were designed to investigate the cytotoxic and anti-proliferative effect of the reference substances (r.s.) of three main chalcone derivatives in nature, namely phloretin, phloridzin and 4-methylchalcone, on the Caco-2 cell line. Overall, the in silico results foremost suggested the potential of phloretin to traverse the blood–brain barrier, and the abilities of phloridzin and nothofagin to act as broad cell enzyme inhibitors; the in vitro results demonstrated that phloretin and 4-methylchalcone have the potential to induce both cytotoxic and anti-proliferative effects, depending on their concentration level: the antiproliferative effects were noticed in the interval from 1 to 50 µg of r.s. per sample, while the cytotoxic effects were noticed from 1 to 50 µg of r.s. per sample in the case of 4-methychalcone, and at 50 µg of r.s. per sample in the case of phloretin. Phloridzin did not affect the viability of the Caco-2 line.