Design, Synthesis, Characterization and Biological Evaluation of Para-Amino Salicylic Acid (PAS) Analogues: An Approach to Repurpose

Abstract

The ever-emerging microbial resistance has imposed great challenges for the medicinal chemist in designing newer chemical entities, which is a lengthy and time-consuming process. An alternate approach of repurposing older drugs can be undertaken to accelerate the discovery of some newer derivatives with lesser side effects. The work reported in the present paper is an extension of the idea of repurposing older drugs. The study aimed to synthesize a series of ester and amide derivatives (P1-P28) of Para-amino salicylic acid. The antimicrobial evaluation of all the synthesized derivatives was performed via the serial dilution method. The Gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis and Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa were used for the antibacterial activity, and Candida albicans were used for the antifungal activity. Ciprofloxacin (antibacterial) and Fluconazole (antifungal) were the standard drugs. The antioxidant evaluation (ester derivatives, P1-P19) was carried out by using the DPPH scavenging method and BHA (butylated hydroxy anisole) was used as the reference. The derivative 5-acetamido-2-(propyl carbamoyl) phenyl acetate (P22) was the most effective antibacterial agent, which may be attributed to the presence of 3-carbon aliphatic alkyl chain. At the same time, 4-methoxy phenyl-4-amino-2-hydroxy benzoate (P15) and 2-chloro phenyl-4-amino-2-hydroxy benzoate (P16) displayed effective antifungal activity. Ethyl-4-amino-2-hydroxy benzoate (P2) demonstrated the most potent free radical scavenging activity. Further, the spectroscopic characterization and physicochemical characterization of the synthesized derivatives have been carried out and were found to be in accord with the assigned structures.