A heterochiral diphenylalanine auxin derivative empowers remarkable mechanical integrity with promising Antiinflammatory and Antimicrobial Performances

Abstract

The emergence of drug-resistant microbes in conjunction with antiinflammatory responses are one of the universal challenges in health care avenues. Although scientists have dedicated enormous efforts to discover potential constructs, much advancement could not be achieved as the available drugs failed to authenticate all the complications together in one shot. Along this perspective, herein our endeavor is to report two thixotropic hydrogelators 1-Naph-L-Phe-D-Phe-OH (Hydrogelator I) and 2-Naph-L-Phe-D-Phe-OH (Hydrogelator II) with an excellent hydrogelation performance as well as high mechanical strength at physiological pH and room temperature. Interestingly they not only revealed stability towards proteolytic degradation on incubation with the proteolytic enzyme Proteinase K but also confirmed biocompatibility when treated with the HEK293 cell line in vitro. Indeed, the temperature dependent NMR, IR and circular dichroism studies compelled us to consider a β-sheet structure in the hydrogelators. However, the inclusion of naphthyl units at appropriate positions in the sequence enlightens a rational strategy towards tweaking the mechanical strength of the hydrogels, one of the benchmarks for biomedical applications. Indeed, the hydrogelators were found to be selective towards Gram-positive bacteria, namely Staphylococcus aureus and S. mutans, and inactive against the Gram negative organisms, namely Escherichia coli and Klebsiella pneumonia. Surprisingly, they not only displayed potency against the fungal strains C. albicans and A. Niger, but also preferential anti-inflammatory behavior in the matrix metalloproteinase receptors MMP2 and MMP9. We anticipate that our designed injectable hydrogelators, blended with the benchmarks under one roof, will contribute to the development of efficient and safe therapeutics to address existing stumbling blocks and improve the human healthcare zone.