Actinobacteria are wide spread in nature and represent the largest taxonomic group within the domain Bacteria. They are abundant in soil and have been extensively explored for their therapeutic applications. This versatile group of bacteria has adapted to diverse ecological habitats, which has drawn considerable attention of the scientific community in recent times as it has opened up new possibilities for novel metabolites that may help in solving some of the most challenging problems of the day, for example, novel drugs for drug-resistant human pathogens, affordable means to maintain ecological balance in various habitats, and alternative practices for sustainable agriculture. Traditionally, free dwelling soil actinobacteria have been the subject of intensive research. Of late, symbiotic actinobacteria residing as endophytes within the plant tissues have generated immense interest as potential source of novel compounds, which may find applications in medicine, agriculture, and environment. In the light of these possibilities, this review focuses on the diversity of endophytic actinobacteria isolated from the plants of extreme habitats and specific ecological niches. Furthermore, an attempt has been made to assign chemical class to the compounds obtained from endophytic actinobacteria. Potential therapeutic applications of these compounds and the utility of endophytic actinobacteria in agriculture and environment are discussed.
31 July 2018 in Current Topics in Medicinal Chemistry
Increased incidences of Candida infection have augmented morbidity and mortality in human population, particularly among severely immunocompromised patients and those having a long stay in hospitals (nosocomial infections). Many virulence factors and fitness attributes are reported to be associated with the pathogenicity of Candida sp. It can cause infections ranging from easily treatable superficial type to life-threatening invasive infections. Additionally, it has the capability to infect humans of all age groups. Indeed, overutilization of broad-spectrum antibiotics has further complicated the scenario by leading the emergence of less sensitive Candida strains especially non-albicans. Despite our developed armamentarium, the diagnosis and treatment of human fungal infections remain a challenge. This review focuses on the prevalence of Candida spp. as human pathogens with emerging resistance to existing anti-fungal drugs. Furthermore, factors and mechanisms contributing to the pathogenicity of Candida spp. and the challenges being faced in combating the devastating infections associated with these pathogens have been discussed. Moreover, pros and cons of the current and future anti-mycotic drugs have been analyzed.
In view of the fast depleting armamentarium of drugs against significant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA) and others due to rapidly emerging drug-resistance, the discovery and development of new drugs need urgent action. In this endeavor, a new strain of endophytic actinobacterium was isolated from the plant Datura metel, which produced secondary metabolites with potent anti-infective activities. The isolate was identified as Streptomyces californicus strain ADR1 based on 16S rRNA gene sequence analysis. Metabolites produced by the isolate had been investigated for their antibacterial attributes against important pathogens: S. aureus, MRSA, S. epidermis, Enterococcus faecium and E. faecalis. Minimum inhibitory concentration (MIC90) values against these pathogens varied from 0.23 ± 0.01 to 5.68 ± 0.20 μg/mL. The metabolites inhibited biofilm formation by the strains of S. aureus and MRSA (Biofilm inhibitory concentration [BIC90] values: 0.74 ± 0.08–4.92 ± 0.49 μg/mL). The BIC90 values increased in the case of pre-formed biofilms. Additionally, the metabolites possessed good antioxidant properties, with an inhibitory concentration (IC90) value of 217.24 ± 6.77 µg/mL for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging. An insight into different classes of compounds produced by the strain ADR1 was obtained by chemical profiling and GC-MS analysis, wherein several therapeutic classes, for example, alkaloids, phenolics, terpenes, terpenoids and glycosides, were discovered.
1 July 2016 in Current Topics in Medicinal Chemistry
Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a post-prandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α-amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor’s metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.
19 December 2019 in Current Topics in Medicinal Chemistry
Background: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs.Methods: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant.Results: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp.Conclusion: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.