An amyloid‐β inspired biocompatible short peptide amphiphile (sPA) molecule was used for controlled and targeted delivery of bioactive silver nanoparticles via transforming sPA nanostructures. Such sPA‐AgNPs hybrid structures can be further used to develop antibacterial materials to combat emerging bacterial resistance. Due to the excellent antibacterial activity of silver, the growth of clinically relevant bacteria was inhibited in the presence of AgNPs‐sPA hybrids. Bacterial tests demonstrated that the high biocompatibility and low cytotoxicity of the designed sPA allow it to work as a model drug delivery agent. It therefore shows great potential in locally addressing bacterial infections. The results of our study suggest that these nanodevices have the potential to trap and then engage in the facile delivery of their chemical payload at the target site, thereby working as potential delivery materials. This system has potential therapeutic value for the treatment of microbiota triggered progression of neurodegenerative diseases.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited S. aureus specifically (MIC 0.25–64 µg/mL). The in vitro cytotoxicity of compounds with MIC < 1 µg/mL against Vero cells led to identification of four compounds ( 20 , 22 , 24 and 25 ) with selectivity index above 10. These four compounds were tested against MDR S. aureus panel. Remarkably, 5-chloro- N -(4’-bromo-3’-trifluoromethylphenyl)-2-hydroxybenzamide ( 22 ) demonstrated excellent activity against nine MRSA and three VRSA strains with MIC 0.031–0.062 µg/mL, which is significantly better than the control drugs methicillin and vancomycin. The comparative time–kill kinetic experiment revealed that the effect of bacterial killing of 22 is comparable with vancomycin. Compound 22 did not synergize with or antagonize any FDA-approved antibiotic and reduced pre-formed S. aureus biofilm better than vancomycin. Overall, study suggested that 22 could be further developed as a potent anti-staphylococcal therapeutic.

Lipopeptide‐inspired lipidation of two short tripeptides, Phe‐Tyr‐β‐Ala and Tyr‐Phe‐β‐Ala leads to a pair of constitutional isomers of short peptide amphiphile (sPA). These two molecules were able to mimic lipopeptides properties and therefore could be used as potential drug delivery vehicles up to target sites. Further, these isomeric peptide amphiphiles were able to synthesize stable silver nanoparticles (AgNPs) in presence of sunlight without using any reducing agents. Interestingly, the presence of AgNPs significantly controls the secondary structures of these two isomeric sPAs and hence their self‐assembly. Therefore, such AgNPs‐sPA nanostructures are further used to develop antibacterial materials. Various microscopy and spectroscopy techniques were used to characterize these nanostructures. The antibacterial analysis demonstrated that owing to high biocompatibility and less cytotoxicity, designed sPA exhibited great potential in locally addressing bacterial infections. Thus, such a strategic design of lipidated tripeptide fragments can be tuned for potential therapeutic value for future applications.

The genus Artocarpus, a nutraceutical, is widely used in traditional medicine for treatment of many chronic diseases including infections. Artocarpus hirsutus Lam., an evergreen tree endogenous to the Western Ghats of India, is a well-documented medicinal plant in Hortus Malabaricus, the oldest comprehensive printed book on the natural plant wealth of Asia. Herein we describe artocarpin, a major isoprenyl flavonoid isolated from the stem bark of A. hirsutus Lam., as the explanation behind the indigenous knowledge reported for treatment of various skin ailments. Artocarpin, a noncytotoxic, isoprenyl flavonoid, is rapidly bactericidal against multiple World Health Organization (WHO) priority 2 pathogens including multidrug-resistant Staphylococcus aureus and Enterococcus sp. with an extended postantibiotic effect. Artocarpin (AH-5) synergizes with gentamicin and linezolid, inhibits bacteria in different physiological states, including under biofilm and in macrophages, and does not induce resistance in S. aureus despite repeated exposure. Artocarpin induces rapid cellular lysis, as confirmed by fluorescence microscopy and scanning electron microscopy analysis as well as by measuring the significantly increased extracellular and concomitantly decreased intracellular adenosine triphosphate levels. When tested in vivo, AH-5 is almost as effective as vancomycin in reducing bacterial load in murine thigh and skin infection models, which is comparable to standard of care (SoC) antibiotics. This is highly significant since AH-5 is a direct natural entity that has been evaluated without any pharmaceutical modification and expresses robust in vitro and in vivo antibacterial activity, which is comparable to highly optimized SoC comparators and further could be considered as an effective clinical, antibacterial drug lead.