Occurrence and intensity of systemic invasive fungal infections have significantly risen in recent decades with large amount of mortality and morbidity rates at global level. Treatment therapy lies on the current antifungal interventions and are often limited due to the emergence of resistance to antifungal agents. Chemosensitization of fungal strains to the conventional antimycotic drugs are of growing concern. Current antifungal drugs often have been reported with poor activity and side effects to the host and have a few number of targets to manifest their efficacy on the pathogens. Indiscriminately, the aforementioned issues have been easily resolved by the development of new intervention strategies. One such approach is to employ combinational therapy that has exhibited a great level of inhibitions than that of a single compound. Chemosensitization of pathogenic mycoses to commercial antifungal drugs could be drastically enhanced by co-application of chemosensitizers along with the conventional drugs. Chemosensitizers could address the resistance mechanisms evolved in the pathogenic fungi and targeting the system to make the organism susceptible to commercially and clinically proven antifungal drugs. However, this strategy has not been overreached to the greater level, but it needs much attention to fight against not only with the pathogen but combat the resistance mechanisms of pathogens to drugs. Natural compounds including plant compounds and microbial proteins act as potential chemosensitizers to break the resistance in mycoses. Aspergillus giganteus, a filamentous fungus, is known to produce a cysteine rich extracellular protein called as antifungal protein (AFP). AFP has shown enhanced efficacy against several filamentous and non-filamentous fungal pathogens. On the basis of the reported studies on its targeted potential against pathogenic mycoses, AFP would be fabricated as a good chemosensitizer to augment the fungicidal efficacy of commercial antimycotic drugs. This paper reviews on breakthrough in the discovery of antifungal drugs along with the resistance patterns of mycoses to commercial drugs followed by the current intervention strategies applied to augment the fungicidal potential of drugs.
Host–guest complexation of decamethoxypillar[5]arene and difunctionalized pillar[4]arene[1]quinone with isatin were demonstrated by 1H NMR titration experiments. The antibacterial potentials of isatin, decamethoxypillar[5]arene, difunctionalized pillar[4]arene[1]quinone and their isatin inclusion complexes were evaluated against both Gram-positive and Gram-negative bacteria by the well-diffusion method. The results of the antibacterial assay revealed that decamethoxypillar[5]arene displayed very good antibacterial activity than the difunctionalized pillar[4]arene[1]quinone. Isatin inclusion complex of decamethoxypillar[5]arene showed very good antibacterial activity as that of chloramphenicol with S. aureus, P. aeruginosa, K. pneumoniae and E. coli. Checkerboard assay revealed synergic effects of P[5]A and isatin combinations against selected microorganisms. In silico toxicity predictions suggested the potential of isatin, decamethoxypillar[5]arene and the difunctionalized pillar[4]arene[1]quinone as prospective drug candidates. Graphical abstract Isatin inclusion complex of decamethoxy pillar[5]arene showed very good antibacterial activity as that of chloramphenicol with S. aureus, P. aeruginosa, K. pneumoniae and E. coli.
Acinetobacter baumannii is an ESKAPE pathogen and threatens human health by generating infections with high fatality rates. A. baumannii leads to a spectrum of infections such as skin and wound infections, endocarditis, meningitis pneumonia, septicaemia and urinary tract infections. Recently, strains of A. baumannii have emerged as multidrug-resistant (MDR), meaning they are resistant to at least three different classes of antibiotics. MDR development is primarily intensified by widespread antibiotic misuse and inadequate stewardship. The World Health Organization (WHO) declared A. baumannii a precarious MDR species. A. baumannii maintains the MDR phenotype via a diverse array of antimicrobial metabolite-hydrolysing enzymes, efflux of antibiotics, impermeability and antibiotic target modification, thereby complicating treatment. Hence, a deeper understanding of the resistance mechanisms employed by MDR A. baumannii can give possible approaches to treat antimicrobial resistance. Resistance-nodulation-cell division (RND) efflux pumps have been identified as the key contributors to MDR determinants, owing to their capacity to force a broad spectrum of chemical substances out of the bacterial cell. Though synthetic inhibitors have been reported previously, their efficacy and safety are of debate. As resistance-modifying agents, phytochemicals are ideal choices. These natural compounds could eliminate the bacteria or interact with pathogenicity events and reduce the bacteria’s ability to evolve resistance. This review aims to highlight the mechanism behind the multidrug resistance in A. baumannii and elucidate the utility of natural compounds as efflux pump inhibitors to deal with the infections caused by A. baumannii.
20 March 2025 in Journal of Asian Natural Products Research
In our study, the functional and biological properties of the developed probiotic formulations containing Lactobacillus plantarum and isatin (Couroupita guianensis) have been evaluated. The developed probiotic formulations have demonstrated remarkable antioxidant, antimicrobial, and cholesterol-lowering properties (67.3 ± 0.57%). In addition, they exhibit high survivability in simulated oral fluid (98.8%). Furthermore, extracellular enzyme production iterates other health attributes of probiotic formulations to the human system by improving the utilization of nutrients in the intestine. In sum, the developed probiotic formulations have unveiled probiotic functions and safer applications, which could pave the way to develop functional foods or lead compounds for drug discovery.