Polysaccharides and lipoproteins as reactants for the synthesis of pharmaceutically important scaffolds: A review.

The growing number of diseases in the past decade has once again highlighted the need for extensive research on the development of novel drugs. There has been a major expansion in the number of people suffering from malignant diseases and types of life-threatening microbial infections. The high mortality rates caused by such infections, their associated toxicity, and a growing number of microbes with acquired resistance necessitate the need to further explore and develop the synthesis of pharmaceutically important scaffolds. Chemical entities derived from biological macromolecules like carbohydrates and lipids have been explored and observed to be effective agents in the treatment of microbial infections and diseases. These biological macromolecules offer a variety of chemical properties that have been exploited for the synthesis of pharmaceutically relevant scaffolds. All biological macromolecules are long chains of similar atomic groups which are connected by covalent bonds. By altering the attached groups, the physical and chemical properties can be altered and molded as per the clinical applications and needs, this ring them potential candidates for drug synthesis. The present review establishes the role and significance of biological macromolecules by articulating various reactions and pathways reported in the literature.

Exploration of novel TOSMIC tethered imidazo[1,2-a]pyridine compounds for the development of potential antifungal drug candidate.

New candidates of imidazo[1,2-a]pyridine were designed by combining 2-amino pyridine, TOSMIC and various assorted aldehydes to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield. The resulting imidazo[1,2-a]pyridine derivatives were structurally verified by 1 HNMR, 13 CNMR, HRMS, and HPLC. The compounds were analyzed for their antioxidant and fluorescent properties and it was observed that compound 15 depicted highest potential. The compounds were evaluated for their antifungal potential to highlight their medical application in the area of Invasive Fungal Infections (IFI). Compound 12 gave the highest antifungal inhibition against Aspergillus fumigatus 3007 and Candida albicans 3018. To elucidate the antifungal mechanism, confocal images of treated fungi were analyzed, which depicted porous nature of fungal membrane. Estimation of fungal membrane sterols by UPLC indicated decrease in ergosterol component of fungal membrane. In silico studies further corroborated with the in vitro results as docking studies depicted interaction of synthesized heterocyclic compounds with amino acids present in the active site of target enzyme (lanosterol 14 alpha demethylase). Absorption, distribution, metabolism, and excretion (ADME) analysis was indicative of drug-likeliness of the synthesized compounds.

Novel nucleosides as potential inhibitors of fungal lanosterol 14α-demethylase: an in vitro and in silico study.

Aim: The global burden of fungal infections has transitioned from a case-specific observation to a major cause of high human mortality. Therefore, novel compounds with innovative methodologies need to be synthesized and evaluated for their antifungal potential to keep pace with the current clinical demands. Results: An efficient synthetic pathway was developed for the synthesis of 21 synthetic novel nucleosides. Two compounds had significant antifungal effect on Aspergillus fumigatus 3007, which was comparable to fluconazole. The experimental data (confocal microscopy, ultrahigh-performance liquid chromatography and flow cytometry) demonstrated the inhibition of fungal lanosterol 14α-demethylase. Conclusion: Owing to the therapeutic relevance of the synthesized nucleosides and simplicity of the procedure, the method may find its potential application for synthesis of antifungal agents.

Improved Production of Thermostable Cellulase from Thermoascus aurantiacus RCKK by Fermentation Bioprocessing and Its Application in the Hydrolysis of Office Waste Paper, Algal Pulp, and Biologically Treated Wheat Straw.

Thermostable cellulases have wide variety of applications and distinctive advantages, but their low titer becomes the hurdle in their commercialization. In the present work, an assessment of optimum levels of significant factors (temperature, moisture ratio, inoculum size, and ammonium sulfate) and the effect of their interactions on production of thermostable CMCase, FPase, and ß-glucosidase by Thermoascus aurantiacus RCKK under solid-state fermentation (SSF) was carried out using central composite design (CCD) of response surface methodology (RSM). The study revealed 33, 13, and 8 % improvement in FPase, CMCase, and ß-glucosidase production, respectively. Moreover, crude cellulase from T. aurantiacus RCKK efficiently hydrolyzed office waste paper, algal pulp (Gracillaria verulosa), and biologically treated wheat straw at 60 °C with sugar release of about 830 mg/ml, 285 mg/g, and 260 mg/g of the substrate, respectively. The thermostable enzyme from T. aurantiacus RCKK holds potential to be used in biofuel industry.

Fungal pretreatment improves amenability of lignocellulosic material for its saccharification to sugars.

The sugarcane bagasse was biologically pretreated with three white-rot fungi; Pleurotus florida, Coriolopsis caperata RCK 2011 and Ganoderma sp. rckk-02, individually under solid-state fermentation. P. florida, C. caperata RCK 2011 and Ganoderma sp. rckk-02 degraded lignin up to 7.91, 5.48 and 5.58%, respectively. The lignocellulolytic enzymes produced by these fungi were also monitored during solid state fermentation of sugarcane bagasse. The fungal fermented sugarcane bagasse when hydrolyzed with crude cellulases from brown-rot fungus, Fomitopsis sp. RCK2010, released comparatively 1.5-2.4 fold higher sugars than in case of untreated sugarcane bagasse. The study demonstrated that white-rot fungal pretreatment improved the amenability of plant material for enzymatic hydrolysis.

Enhanced exoglucanase production by brown rot fungus Fomitopsis sp. RCK2010 and its application for cellulose saccharification.

Exoglucanase production by brown rot fungus Fomitopsis sp. RCK2010 was optimized under solid-state fermentation using Plackett-Burman design (PBD) and response surface methodology (RSM). Four fermentation variables (moisture, inoculum level, casein, and Triton X-100) were identified to effect cellulase production significantly by PBD, which were further optimized using RSM of central composite design. An overall 130 % increase in enzyme production was achieved by the optimization of variables using statistical approaches. Moreover, crude cellulase from Fomitopsis sp. RCK2010 was applied to saccharify pretreated Prosopis juliflora (cellulosic fraction), which resulted in the release of 327.35 mg/g of reducing sugars that could further be utilized for bioethanol production.

Application of lignocellulolytic enzymes produced under solid state cultivation conditions.

In this paper, cellulose from brown-rot fungus Fomitopsis sp. RCK2010, thermostable and alkalostable xylanase from Bacillus pumilus MK001 and laccase from Ganoderma sp. rckk-02 were evaluated for (i) saccharification of alkali pretreated rice straw and wheat straw, (ii) upgradation of chick feed and (iii) decolorization of dyes, respectively. The cellulose from brown-rot fungus resulted in a sugar release of 151.48 and 214.11 mg/g, respectively, from rice straw and wheat straw, which was comparatively higher than the earlier reports. While xylan, one of the main anti-nutritional factors (ANFs) present in the chick feed was removed to an extent of 11.6 mg/g xylose sugars at 50°C using the thermostable xylanase. Besides, the treatment with thermostable xylanase also brought about a release of 0.85 (mg/g) of soluble phosphorous. Moreover, the laccase when used for the decolorization of Remazol Brilliant Blue R (RBBR) and xylidine ponceau cause almost complete decolorization in 2 and 4h, respectively, depicting high rate of decolorization.

Optimization of cellulase production by a brown rot fungus Fomitopsis sp. RCK2010 under solid state fermentation.

Culture conditions for enhanced cellulase production from a newly isolated brown rot fungus, Fomitopsis sp. RCK2010 were optimized under solid state fermentation. An initial pH of 5.5 and moisture ratio of 1:3.5 (solid:liquid) were found to be optimal for maximum enzyme production. Of the different carbon sources tested wheat bran gave the maximum production of CMCase (71.526 IU/g), FPase (3.268 IU/g), and ß-glucosidase (50.696 IU/g). Among the nitrogen sources, urea caused maximum production of CMCase (81.832 IU/g), where as casein and soyabean meal gave the highest FPase (4.682 IU/g) and ß-glucosidase (69.083 IU/g) production, respectively. Among amino acids tested glutamic acid gave the highest production for CMCase (84.127I U/g); however 4-hydroxy-l-proline stimulated maximum FPase production (6.762 IU/g). Saccharification of pretreated rice straw and wheat straw by crude enzyme extract from Fomitopsis sp. RCK2010 resulted in release of 157.160 and 214.044 mg/g of reducing sugar, respectively.