2. Academic Validation
  3. 4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

  • Biomolecules. 2019 Dec 19;10(1):9. doi: 10.3390/biom10010009.
Martin Krátký 1,  Klára Konečná 2,  Jiří Janoušek 3,  Michaela Brablíková 4,  Ondřej Janďourek 2,  František Trejtnar 3,  Jiřina Stolaříková 5,  Jarmila Vinšová 1
Affiliations

Affiliations

  • 1 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
  • 2 Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
  • 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
  • 4 Unipetrol Centre of Research and Education, 436 70 Litvínov-Záluží 1, Czech Republic.
  • 5 Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské námĕstí 7, 702 00 Ostrava, Czech Republic.
PMID: 31861596 DOI: 10.3390/biom10010009
Abstract

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.

Keywords

4-aminobenzoic acid; Schiff bases; antibacterial activity; antifungal activity; cytotoxicity; synthesis; vitamin.

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