The present manuscript demonstrated an efficient microwave assisted Multicomponent reaction approach in modifying the existing drug 5-fluorocytosine (Flucytosine). Previously reported flucytosine-based hybrids exhibited antifungal activity largely in combination with standard drugs, therefore not act as standalone agents/drugs. In contrast, the current methodology generated two diversity points on a single molecule by utilizing one class (nucleoside analogue, 5-Fluorocytosine) of antifungals as a reactant and generating the second class (azole) of antifungal within the molecule through GBB reaction approach leads to hybrid pharmacophores with enhanced potential as compared to reported drugs. Among all the tested compounds, compound (4 h) depicted higher antifungal activity against Aspergillus fumigatus when compared to reported drugs 5-flucytosine and fluconazole with MIC value of 0.312 mg/ml.

A series comprising 20 novel benzenesulfonamide bearing 1.2.3-triazoles 6a-6d, 7a-7d, 8a-8d, 9a-9d, 10a-10d has been synthesized and investigated as antifungal agents. The synthesized compounds were tested against two fungal strains Aspergillus fumigatus 3007 and Candida albicans 3018. Among the tested compounds, three gave the lowest inhibitory concentration of 0.039 (mg/ml) against A. fumigatus 3007 and two compounds gave the lowest inhibitory concentration of 0.019 mg/ml against C. albicans 3018. The antifungal potential of the synthessied compounds was in par with the reported drug fluconazole. To elucidate the antifungal mechanism of the synthesized compounds confocal images of the treated fungal cells were analysed. The cells depicted porous nature of fungal membrane indicating the probable inhibition of fungal lanosterol 14-α demethylase enzyme. In silico tools like molecular docking, ADME analysis including physicochemical properties, lipophilicity, solubility in water, pharmacokinetic properties, drug likeness, medicinal chemistry properties and toxicity analysis was also carried to establish the significance of the synthesized compounds.

The pursuit of novel therapeutic agents with potent anticancer activity remains a key priority in medicinal chemistry, particularly for addressing liver and stomach malignancies, which continue to present substantial clinical challenges. In this study, we have reported the synthesis and biological assessment of a new series of novel 1,4-Dihydropyridine (DHP) tethered Isatin scaffolds, aimed at identifying promising candidates with significant anticancer potential. A combined approach of in-silico ADMET analysis, molecular docking and in-vitro cytotoxic screening was employed. The ADMET predictions indicated favorable pharmacokinetic profiles and minimal toxicity for most of the compounds. Molecular docking revealed strong binding with CDK2, supporting their anticancer potential. Compounds P3, P6, P7, P10, P11, and P12 demonstrated substantial anticancer activity against HepG2 (liver cancer) and AGS (gastric cancer) cell lines when compared to cisplatin, with P11 being the most potent (IC50 = 18.61 μM for HepG2 and 26.55 μM for AGS). Additionally, antifungal evaluation revealed only marginal activity against A. fumigatus 3007. These findings establish 1,4-DHP-isatin hybrids as promising lead compounds for further development in anticancer and antifungal drug discovery.

Smart polymers represent a class of advanced materials that undergo reversible changes in their physical or chemical form and are known as responsive polymers. These polymers show transitions when external stimuli, such as temperature and pH, come into play. Smart polymers are being increasingly applied in various fields, such as drug delivery to a targeted site and gene therapy. They also play a pivotal role in tissue engineering, environmental sensors, and the development of shape memory polymers. Despite their major challenges, they remain effective in overcoming significant barriers. It can be said that these polymers have the potential to revolutionize various fields. This review highlights the underlying types and applications of smart polymers, emphasizing their roles in the future.

Multicomponent reactions (MCRs) have significant relevance in the field of synthetic chemistry, and in recent times one of the MCR variants, named the Groebke-Blackburn-Bienaymé (GBB) reaction, has attracted massive attention for the synthesis of biologically important scaffolds. The present review elaborates on the chemical advancement reported for the GBB reaction with an emphasis on the role of various catalytic systems. Further, the role of the GBB reaction has been redefined as a standard protocol for the synthesis of an array of potential bioactive compounds.

Fungi are a diverse group of organisms that play an essential role in the biosphere.

The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like chitosan hold unique structural properties and thus can be utilized in the synthesis of biologically important scaffolds. To address the current scenario, the author's synthesized novel chitosan-azetidine derivative by adopting one-pot multicomponent reaction approach. The influence of chemical modification on the structural characteristics was investigated by means of spectroscopic techniques viz. FT-IR and 1HNMR and elemental analysis. Additionally, the authors investigated the antifungal potential of chitosan-azetidine derivative against Aspergillus fumigatus 3007 and the results indicated higher antifungal effect with an antifungal inhibitory index of 26.19%. The SEM and confocal microscopy images also reflected a significant inhibitory effect on the morphology of fungal mycelia, thus reflecting the potential of synthesized chitosan-azetidine derivativeas a potential antifungal agent.

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.

The reaction of TOSMIC with highly functionalized imines has been reported. The use of monomeric silica as a catalyst for the reaction has been reported for the first time. The main product of the reported green methodology, formed by the sequential attack of the two TOSMIC units upon the carbon-nitrogen double bond of highly functionalized imines, has been identified as bis(tosylmethyl)azetidine, a four member N-heterocyclic system. The scope of the reaction concerning functionalized imines and TOSMIC reactivity has been studied and determined, keeping in view the advantage of using TOSMIC as component B for the ABB-type cycloaddition reactions.

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.

The fungal diseases represent an increasing global health burden and have transformed from a rare curiosity to the leading cause of human mortality. The present manuscript reports the antifungal potential of two novel compounds possessing a carbohydrate and an imidazole moiety. Antifungal susceptibility test determined the growth inhibition potential of the synthesized compounds against Aspergillus niger 9689 and it was observed that compounds D and E gave an antifungal inhibitory index of 66.66 and 56.67% respectively. Further, ultra-structure analysis of the treated fungal mycelia through scanning electron microscope (SEM) and confocal microscopy indicated significant membrane permeability and disintegration of fungal cell membrane, thus highlighting the probable role of the synthesized compounds as inhibitors of fungal lanosterol 14α-demethylase. In silico studies corroborated with the in-vitro results, as the synthesized compounds interacted with the critical amino acids present at the active site of the fungal enzyme (lanosterol 14α-demethylase).

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.

In search of potent and novel antifungal agents, herein, the authors report the synthesis, chemical characterization and biological evaluation of triazole tethered glycoconjugates. The structural verification of the molecules was carried out by C-13 NMR, H-1 NMR and mass spectra analysis. The in vitro antifungal activity was investigated against three filamentous fungi, Trichoderma viride 4329, Aspergillus fumigatus 3007 and Sporothrix schenckii. Among the synthesized compounds, it was observed that compound 10f completely inhibited the fungal growth giving a Minimum Inhibitory Concentration (MIC) value of 800 g/ml against Aspergillus fumigatus 3007. Moreover through microscopic analysis, using Scanning Electron Microscopy and confocal imaging, it was detected that the compound had induced pronounced irreversible membrane damage and disruption of fungal mycelium.

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 β-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 β-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.

Lignocellulosic biomass has been considered as an important and sustainable source of renewable energy. Cellulose constitutes the major component of the lignocellulosic biomass and also offers maximum recalcitrance towards its fullest utilization. The enzymatic breakdown of cellulose is achieved through cellulases. Diverse forms of microbes including fungi, bacteria, actinomycetes and yeast are known to produce cellulases that have found extensive application in various industries. Due to the current global political unrest over oil prices and the threat of global warming following combustion of fossil fuels, the paradigm of research is now focused on biofuel production from plant biomass. Conventional approaches have not been economically feasible for meeting the demands of the industry. This review provides an update regarding the status of present microbial cellulase production technologies and research with special reference to solid state fermentation and different molecular techniques such as mutagenesis, metabolic engineering and heterologous gene expression of cellulases from different microbial domains with improved catalytic and stability properties. Metagenomic and genomic studies for mining of novel cellulase genes in addition to screening of culturable strains using conventional methods have been advanced. In addition the bottlenecks associated with cellulase production and how the future research needs to be directed to provide a comprehensive technology for the production of cellulases with novel traits for application at an industrial level without economic constraints are discussed.

A mutant strain of Trichoderma asperellum RCK2011 was developed through UV-irradiation for enhanced cellulase production and lower catabolite repression. The production of FPase, CMCase and beta-glucosidase was optimized under solid state fermentation; up to 20 mM of glucose did not inhibit cellulase production. The mutant strain T. asperellum SR1-7 produced FPase (2.2 IU/gds), CMCase (13.2 IU/gds), and b-glucosidase (9.2 IU/gds) under optimized conditions, which is, 1.4, 1.3, 1.5-fold higher than the wild type. The wild as well as mutant strain produced the cellulases at pH range, 4.0-10.0. Saccharification of pretreated corn cob, wheat straw, and sugarcane bagasse by cellulase from mutant strain SR1-7 resulted in release of reducing sugar at the rate of 530.0 mg/g, 290.0 mg/g, and 335.0 mg/g of substrate, respectively; this is 1.6-fold higher than the wild type strain. (C) 2014 Elsevier Ltd. All rights reserved.

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.

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.

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.