4-aminobenzoic acid derivatives: Converting folate precursor to antimicrobial and cytotoxic agents

Article abstract of DOI:10.3390/biom10010009

4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 μM), moderate antimycobacterial activity (MIC ≥ 62.5 μM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 μM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC50 ≥ 15.0 μM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.