Optimization of pullulan production by Aureobasidium pullulans using semi-solid-state fermentation and artificial neural networks: Characterization and antibacterial activity of pullulan impregnated with Ag-TiO2 nanocomposite.

This study presents a novel and efficient approach for pullulan production using artificial neural networks (ANNs) to optimize semi-solid-state fermentation (S-SSF) on faba bean biomass (FBB). This method achieved a record-breaking pullulan yield of 36.81 mg/g within 10.82 days, significantly exceeding previous results. Furthermore, the study goes beyond yield optimization by characterizing the purified pullulan, revealing its unique properties including thermal stability, amorphous structure, and antioxidant activity. Energy-dispersive X-ray spectroscopy and scanning electron microscopy confirmed its chemical composition and distinct morphology. This research introduces a groundbreaking combination of ANNs and comprehensive characterization, paving the way for sustainable and cost-effective pullulan production on FBB under S-SSF conditions. Additionally, the study demonstrates the successful integration of pullulan with Ag@TiO2 nanoparticles during synthesis using Fusarium oxysporum. This novel approach significantly enhances the stability and efficacy of the nanoparticles by modifying their surface properties, leading to remarkably improved antibacterial activity against various human pathogens. These findings showcase the low-cost production medium, and extensive potential of pullulan not only for its intrinsic properties but also for its ability to significantly improve the performance of nanomaterials. This breakthrough opens doors to diverse applications in various fields.

Multifaceted chemical and bioactive features of Ag@TiO2 and Ag@SeO2 core/shell nanoparticles biosynthesized using Beta vulgaris L. extract.

Due to increasing concerns about environmental impact and toxicity, developing green and sustainable methods for nanoparticle synthesis is attracting significant interest. This work reports the successful green synthesis of silver (Ag), silver-titanium dioxide (Ag@TiO2), and silver-selenium dioxide (Ag@SeO2) nanoparticles (NPs) using Beta vulgaris L. extract. Characterization by XRD, SEM, TEM, and EDX confirmed the successful formation of uniformly distributed spherical NPs with controlled size (25 ± 4.9 nm) and desired elemental composition. All synthesized NPs and the B. vulgaris extract exhibited potent free radical scavenging activity, indicating significant antioxidant potential. However, Ag@SeO2 displayed lower hemocompatibility compared to other NPs, while Ag@SeO2 and the extract demonstrated reduced inflammation in a carrageenan-induced paw edema animal model. Interestingly, Ag@TiO2 and Ag@SeO2 exhibited strong antifungal activity against Rhizoctonia solani and Sclerotia sclerotium, as evidenced by TEM and FTIR analyses. Generally, the findings suggest that B. vulgaris-derived NPs possess diverse biological activities with potential applications in various fields such as medicine and agriculture. Ag@TiO2 and Ag@SeO2, in particular, warrant further investigation for their potential as novel bioactive agents.

Turmeric extract-mediated biogenic synthesis of Ag@SeO2 magnetic nanoparticles: characterization, optimization, antibacterial and antioxidant activities.

This study bio-synthesized Ag@SeO2 bmNPs successfully, using turmeric ethanol extract, and characterized them using various techniques. The FT-IR analysis reveals the involvement of these plant-derived compounds, especially phenolics, in the reduction process by acting as electron donors and stabilizing/capping agents. Zeta potential analysis showed a slight negative surface charge for the stability of Ag@SeO2 NPs, where TEM revealed spherical nanoparticles with an average size of 20 nm. The XRD confirmed crystallinity and a core-shell structure, and EDX identified elements consistent with Ag@SeO2 and a 3 : 1 Ag/Se atomic ratio. Further, SEM supported the spherical shape and uniform size. These findings highlight the successful biosynthesis of Ag@SeO2 bmNPs with promising properties for diverse applications. Moreover, the Box-Behnken design (BBD) and artificial neural network (ANN) model were engaged to optimize Ag@SeO2 bmNP biosynthesis. BBD identified significant influences of pH, bioconversion temperature, time, and turmeric concentration on bmNP yield, with adjusted R2 and predictive R2 being 0.9075 and 0.8829, respectively. However, its limitations were revealed by a significant lack of fit. ANN modeling with a 3-5-7-1 topology showed superior predictive accuracy and identified optimal conditions for maximizing yield (pH 9.83, 51.7 °C, 1.0 h, 3.71 mg mL-1 turmeric). Validation experiments confirmed the model's reliability. Turmeric extract exhibited significantly higher amounts of phenolics, and flavonoids compared to the bmNPs, suggesting its potential for strong antioxidant activity. Both turmeric extract and bmNPs displayed antioxidant activity in ABTS and DPPH assays, with turmeric extract being the most potent due to its curcuminoid content. The potential activity of Ag@SeO2 bmNPs against S. aureus, K. pneumonia, E. coli, and B. cereus was investigated, with inhibition zones ranging from 22 to 32 mm. The MIC values of tested NPs towards pathogenic bacteria ranged from 165.625 and 331.25 µg mL-1.

Synthesis of novel benzopyrimido[4,5-d]azoninone analogs catalyzed by biosynthesized Ag-TiO2 core/shell magnetic nanocatalyst and assessment of their antioxidant activity.

The present work reported the synthesis of novel benzopyrimido[4,5-d]azoninone analogs using a biosynthesized Ag-TiO2 core/shell magnetic nanocatalyst. Accordingly, three-component one-pot reactions of benzoazonine-dione with thiourea and aryl aldehyde derivatives under nanocatalytic and optimized conditions afforded reasonable to brilliant yields of the target products (57-91%). The nanocatalyst was synthesized by a facile method using turmeric ethanol extract as a reducing and chelating agent. The synthesized nanocatalyst was verified by FT-IR, XRD, zeta potential, EDX, SEM, and TEM. The nanocatalyst presented remarkable catalytic activity for the synthesis of the target products. The procedure provided biosynthesis of the nanocatalyst, accessible reagents, high yields and rates of the reactions, nanocatalyst recyclability, and ease of product isolation and purification. The novel products were characterized by FT-IR, 1H-NMR, 13C-NMR, mass spectra, and 2D NMR analysis (COSY, NOESY, HMQC & HSQC) spectral analyses. The antioxidant activity was assessed by DPPH and phosphomolybdate assays, in which the compounds exhibited excellent potency. Overall, this approach could be used to develop new and sustainable methods for the synthesis of antioxidants and other biologically active molecules.

Synthesis, biological activities, and future perspectives of steroidal monocyclic pyridines.

Steroidal pyridines are a class of compounds that have been the subject of extensive research in recent years due to their potential biological activities. The introduction of a pyridine ring into the steroid skeleton can significantly alter the chemical and biological properties of the compound, making it more potent and/or selective for a particular target. Different synthetic methods have been developed for the preparation of steroidal pyridines. This review provides an overview of the synthesis, biological activities, and future perspectives of steroidal monocyclic dihydropyridines, tetrahydropyridines, and pyridines from 2005 to the present. The different synthetic methods that have been developed for the preparation of these steroids are discussed, as well as the proposed mechanisms and the biological activities that have been reported. Finally, the potential of steroidal monocyclic pyridines for the development of new drugs is discussed. This review is intended to provide a comprehensive overview of the field of steroidal monocyclic pyridines for researchers and scientists who are interested in this area of research. It is also hoped that this review will stimulate further research into the synthesis and biological activities of steroidal pyridines to develop new and improved drugs for the treatment of diseases.

A Comparative Study of Cr(VI) Sorption by Aureobasidium pullulans AKW Biomass and Its Extracellular Melanin: Complementary Modeling with Equilibrium Isotherms, Kinetic Studies, and Decision Tree Modeling.

Melanin as a natural polymer is found in all living organisms, and plays an important role in protecting the body from harmful UV rays from the sun. The efficiency of fungal biomass (Aureobasidium pullulans) and its extracellular melanin as Cr(VI) biosorbents was comparatively considered. The efficiency of Cr(VI) biosorption by the two sorbents used was augmented up to 240 min. The maximum sorption capacities were 485.747 (fungus biomass) and 595.974 (melanin) mg/g. The practical data were merely fitted to both Langmuir and Freundlich isotherms. The kinetics of the biosorption process obeyed the pseudo-first-order. Melanin was superior in Cr(VI) sorption than fungal biomass. Furthermore, four independent variables (contact time, initial concentration of Cr(VI), biosorbent dosage, and pH,) were modeled by the two decision trees (DTs). Conversely, to equilibrium isotherms and kinetic studies, DT of fungal biomass had lower errors compared to DT of melanin. Lately, the DTs improved the efficacy of the Cr(VI) removal process, thus introducing complementary and alternative solutions to equilibrium isotherms and kinetic studies. The Cr(VI) biosorption onto the biosorbents was confirmed and elucidated through FTIR, SEM, and EDX investigations. Conclusively, this is the first report study attaining the biosorption of Cr(VI) by biomass of A. pullulans and its extracellular melanin among equilibrium isotherms, kinetic study, and algorithmic decision tree modeling.

A comparative study using response surface methodology and artificial neural network towards optimized production of melanin by Aureobasidium pullulans AKW.

The effect of three independent variables (i.e., tyrosine, sucrose, and incubation time) on melanin production by Aureobasidium pullulans AKW was unraveled by two distinctive approaches: response surface methodology (i.e. Box Behnken design (BBD)) and artificial neural network (ANN) in this study for the first time ever using a simple medium. Regarding BBD, sucrose and incubation intervals did impose a significant influence on the output (melanin levels), however, tyrosine did not. The validation process exhibited a high consistency of BBD and ANN paradigms with the experimental melanin production. Concerning ANN, the predicted values of melanin were highly comparable to the experimental values, with minor errors competing with BBD. Highly comparable experimental values of melanin were achieved upon using BBD (9.295 ± 0.556 g/L) and ANN (10.192 ± 0.782 g/L). ANN accurately predicted melanin production and showed more improvement in melanin production by about 9.7% higher than BBD. The purified melanin structure was verified by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction pattern (XRD), and thermogravimetric analysis (TGA). The results verified the hierarchical architecture of the particles as small compasses by SEM analysis, inter-layer spacing in the XRD analysis, maximal atomic % for carbon, and oxygen atoms in the EDX analysis, and the great thermal stability in the TGA analysis of the purified melanin. Interestingly, the current novel endophytic strain was tyrosine-independent, and the uniquely applied ANN paradigm was more efficient in modeling the melanin production with appreciate amount on a simple medium in a relatively short time (168 h), suggesting additional optimization studies for further maximization of melanin production.

Synthesis and biological activities of bicyclic pyridines integrated steroid hybrid.

Reports on structural modification of heterosteroids through various reactions, and developed synthetic routes have considerably increased over the last decade. The present review encompasses the applicable approaches dealing with the utility of reactive moieties in various steroids for the synthesis of fused bicyclic pyridines, and binary bicyclic pyridines all over the years. The different sections include the synthesis of steroids-fused, and binary quinolines, pyridopyrimidines, imidazopyridines, spirocyclic imidazopyridines, pyrazolopyridines, thienopyridines, pyridinyl-thiazoles, and tetrazolopyridine hybrids, as well as, the diverse biological applications of these heterocyclic steroids. The researchers' interest was principally focused on investigating the flexibility of synthetic strategies for various derivatives of natural steroids and building proposals based on heterocyclic steroids for drug discovery, biological assessments, and synthetic applications.

Synthetic strategies of heterocycle-integrated pyridopyrimidine scaffolds supported by nano-catalysts.

Nano-catalysts are of special character for the synthesis of organic molecules with high efficiency, and exceptional physicochemical properties. The objective of this study was to present an overview of the literature reports concerning the synthetic strategies supported by nano-catalysts and the biological features of heterocycle-integrated pyridopyrimidine scaffolds. The basic topics include the strategies that were adopted to prepare pyrido[2,3-d]pyrimidines and pyrido[1,2-a]pyrimidines. The synthesis of pyrido[2,3-d]pyrimidines was attained through two-, three-, or four-component reactions. The synthesis of spirocyclic systems, including spiro[indoline-pyridopyrimidine] derivatives and arylation reactions, was investigated. The anticipated mechanisms of the diverse target products, in addition to the preparation of the nanocatalysts, were scrutinized. The privileged antimicrobial characteristics, challenges, literature overview, and future prospectives were consistently investigated.

Developments of pyridodipyrimidine heterocycles and their biological activities.

The entitled review aimed to assemble and highlight the synthetic approaches and biological aspects of heterocycles with pyridodipyrimidine motifs. The recent synthetic approaches were categorized according to the accomplishments of the approaches under catalyst or catalyst-free conditions. The topic involved the synthesis of substituted tricyclic systems and spirocyclic systems. The present study offered an overview of the recent literature in addition to a scope of the preceding literature. The proposed mechanisms of the varied target products were discussed. Pyridodipyrimidine displayed potential and privileged cytotoxic, antioxidant, and antimicrobial performances. The competitions, challenges, and prospects are also deliberated.

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5-a]pyrimidine scaffold.

Pyrazolo[1,5-a]pyrimidines are the dominant motif of many drugs; for instance, zaleplon and indiplon are sedative agents and ocinaplon was identified as an anxiolytic agent. The importance of this class of compounds lies in its varied and significant biological activities, and accordingly, considerable methods have been devised to prepare these compounds. Hence, other derivatives of this class of compounds were prepared by substitution reactions with different nucleophiles exploiting the activity of groups linked to the ring carbon and nitrogen atoms. The methods used vary through the condensation reactions of the aminopyrazoles with 1,2-allenic, enaminonitriles, enaminones, 1,3-diketones, unsaturated nitriles, or unsaturated ketones. Alternatively, these compounds are prepared through the reactions of acyclic reagents, as these methods were recently developed efficiently with high yields. The current review highlighted the recent progress of the therapeutic potential of pyrazolo[1,5-a]pyrimidines as antimicrobial, anticancer, antianxiety, anti-proliferative, analgesic, and antioxidant agents, carboxylesterase, translocator protein and PDE10A inhibitors, and selective kinase inhibitors.

Innovative binary sorption of Cobalt(II) and methylene blue by Sargassum latifolium using Taguchi and hybrid artificial neural network paradigms.

The present investigation has been designed by Taguchi and hybrid artificial neural network (ANN) paradigms to improve and optimize the binary sorption of Cobalt(II) and methylene blue (MB) from an aqueous solution, depending on modifying physicochemical conditions to generate an appropriate constitution for a highly efficient biosorption by the alga; Sargassum latifolium. Concerning Taguchi's design, the predicted values of the two responses were comparable to actual ones. The biosorption of Cobalt(II) ions was more efficient than MB, the supreme biosorption of Cobalt(II) was verified in run L21 (93.28%), with the highest S/N ratio being 39.40. The highest biosorption of MB was reached in run L22 (74.04%), with a S/N ratio of 37.39. The R2 and adjusted R2 were in reasonable values, indicating the validity of the model. The hybrid ANN model has exclusively emerged herein to optimize the biosorption of both Cobalt(II) and MB simultaneously, therefore, the ANN model was better than the Taguchi design. The predicted values of Cobalt(II) and MB biosorption were more obedience to the ANN model. The SEM analysis of the surface of S. latifolium showed mosaic form with massive particles, as crosslinking of biomolecules of the algal surface in the presence of Cobalt(II) and MB. Viewing FTIR analysis showed active groups e.g., hydroxyl, α, ß-unsaturated ester, α, ß-unsaturated ketone, N-O, and aromatic amine. To the best of our knowledge, there are no reports deeming the binary sorption of Cobalt(II) and MB ions by S. latifolium during Taguchi orthogonal arrays and hybrid ANN.

Recent progress in the chemistry of ß-aminoketones.

The ß-aminoketone moiety has been found to be the basic skeleton of several drugs such as the amine salts "tolperisone (vasodilation)" and "oxyfedrine (therapeutic coronary disease)", and fluoroaryl derivatives such as "sitagliptin (antidiabetic)". The objective of this review is to summarize and highlight the chemistry of compounds reported with a ß-aminoketone core in the last five years regarding their synthetic strategies, chemical reactivity, and mechanistic synthetic pathways. In the different sections, we categorize the synthesis of ß-aminoketones by Mannich reactions via catalytic, non-catalytic, and one-pot procedures. Also, the synthesis of the investigated compounds is accomplished by condensation reactions, from propargylic alcohols, reductive hydroamination, alkylation, carbonylative coupling, and acid hydrolysis of metal complexes. The aim of this review is to provide details for the synthesis of piperidines, morpholinones, piperazinones, dihydroxy-2-oxopyrroles, spirocyclic systems, imidazolines, indolizines, pyrido-isoindoles, aminoalcohols, metal complexes, fluoxetine, sotolon, (S)-ketamine, indolines, and benzoazepinones.

Insights into the recent progress in the medicinal chemistry of pyranopyrimidine analogs.

Heterocycles containing the pyranopyrimidine motif have attracted the interest of researchers in recent decades due to their ability to synthesize and explore at a large scale to explore the biological diversity. Therefore, this review highlights the biological characteristics and synthetic approaches adopted to prepare pyranopyrimidine analogs in the last five years. Several novel preparation procedures have been summarized to synthesize these compounds using ionic, basic, or nanocatalysts or catalyst-free conditions to obtain these compounds in good yields. Pyranopyrimidines could also be used as ligands in the preparation of metal complexes with increased biological potency. The different sections include the antimicrobial, antitubercular, antimalarial, antiviral "SARS-CoV-2 inhibitors", antidiabetic, antitumor, cytotoxic, antiinflammatory, antioxidant, anticoagulant, urease inhibitory activities, and tyrosine inhibitors. The results are discussed based on the structure-activity relationships (SARs) and the mechanism of action.

Recent advancements in the multicomponent synthesis of heterocycles integrated with a pyrano[2,3-d]pyrimidine core.

Heterocyclic compounds incorporated with a pyranopyrimidine skeleton have received substantial consideration owing to their privileged, and intelligible biodiversity. Accordingly, this review highlights the multicomponent synthetic routes adopted to prepare heterocyclic compounds incorporated with the pyrano[2,3-d]pyrimidine skeleton in the preceding two years. The different sections comprise the synthesis of bicyclic, tricyclic, polycyclic, and spirocyclic systems along with the estimation of the probable mechanistic routes for the reaction pathways. Commonly, the pyran ring closure was the major idea of most studies, and the mechanistic pathways of these reactions involved Knoevenagel condensation, Michael addition, and intramolecular cyclocondensation. Besides, the significant biological potency of the compounds recently synthesized from multicomponent reactions is deliberated.

Bicyclic 5-6 Systems: Comprehensive Synthetic Strategies for the Annulations of Pyrazolo[ 1,5-a]pyrimidines.

Pyrazolopyrimidines are a privileged class of 5-6 bicyclic systems with three or four nitrogen atoms, including four possible isomeric structures. The significance of this class of compounds is that they can be applied in medical and pharmaceutical fields due to their unlimited biological aptitude, hence it is the basic skeleton of several synthetic drugs. The current review aimed to highlight all the synthetic routes that have been applied to construct the pyrazolo[1,5-a]pyrimidine ring systems up to date. The sections in this study included the synthesis of pyrazolo[1,5- a]pyrimidines by condensation reactions of 5-aminopyrazoles with each of ß-diketones, 1,5-diketones, ß- ketoaldehydes, α-cyanoaldehydes, ß-enaminones, enamines, enaminonitriles, ethers, with unsaturated ketones, unsaturated thiones, unsaturated esters, unsaturated dienones "1,2-allenic", unsaturated aldehydes, unsaturated imines, and unsaturated nitriles. The routes adopted to synthesize this class of heterocyclic compounds were extended for ring construction from acyclic reagents and multicomponent reactions under catalytic or catalyst-free conditions.

Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine scaffolds.

Heterocycles incorporating a pyrimidopyrimidine scaffold have aroused great interest from researchers in the field of medical chemistry because of their privileged biological activities; they are used as anti-bacterial, antiviral, anti-tumor, anti-allergic, antihypertensive, anticancer, and hepatoprotective agents. Therefore, the present study aims to investigate the chemistry of heterocycles incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine skeletons and their biological characteristics. The main sections discuss (1) the synthetic routes to obtain substituted pyrimidopyrimidines, pyrimido[1,6-a]pyrimidin-diones, pyrimidoquinazolines, tricyclic, tetracyclic, and binary systems; (2) the reactivity of the substituents attached to the pyrimidopyrimidine skeleton, including thione and amide groups, nucleophilic substitutions, condensations, ring transformations, and coordination chemistry; (3) compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristics.

Heterocyclic steroids: Efficient routes for annulation of pentacyclic steroidal pyrimidines.

Steroids are components of cell membranes, signaling molecules and are a type of secondary metabolites as a result of their high impact of biological significance. The present review described the literature reports of pentacyclic steroidal pyrimidines as a type of heterocyclic steroids. The main sections included the synthesis of the investigated steroids fused at rings-A or B or D of steroid skeleton, synthesis of binary or linked-type pyrimidines, pyrimidine oxides, macromolecules and mono- or di- or tri-peptides linked-steroidal pyrimidines. Besides, the present research highlighted the biological significance of steroidal pyrimidines, in which the compounds revealed potent anticancer, antioxidant, antibacterial, and anti-Alzheimer agents. In addition, some hetero-steroids were screened for binding DNA assay and gene expression analysis. It was settled that the incorporation of pyrimidine scaffold into steroid basic skeleton is crucial for better biological results.

Bicyclic 6 + 6 systems: the chemistry of pyrimido[4,5-d]pyrimidines and pyrimido[5,4-d]pyrimidines.

The present study provides an overview of the chemistry and biological significance of pyrimido[4,5-d]pyrimidine and pyrimido[5,4-d]pyrimidine analogs as types of bicyclic [6 + 6] systems. The main sections include: (1) synthesis methods; (2) the reactivities of the substituents linked to the ring carbon and nitrogen atoms; and (3) biological applications. A discussion demonstrating the proposed mechanisms of unexpected synthetic routes is intended. The aim of this study is to discuss the synthetic significance of the titled compounds and to establish the biological characteristics of this class of compounds as studied to date, where the compounds have been applied on a large scale in the medical and pharmaceutical fields. This survey will help researchers in the fields of synthetic organic and medicinal chemistry to undertake and improve new approaches for the construction of new standard biological components.

Advances in the Chemistry of 6-6 Bicyclic Systems: Chemistry of Pyrido[3,4- d]pyrimidines.

The aim of this work is to discuss the chemistry of pyrido[3,4-d]pyrimidines as one of the most important heterocyclic compounds with remarkable synthetic, biological and medical applications. In this overview, the chemistry of heterocyclic compounds incorporated the pyrido[3,4-d]pyrimidine scaffold as demonstrated by chemical reactions and different preparation processes. The anticipated compounds were synthesized from pyridine or pyrimidine compounds and a description of the reactivity of substituents attached to ring carbon and nitrogen atoms is discussed. On the other hand, the synthesis and reactions of fused heterocycles incorporated pyrido[3,4-d]pyrimidine scaffold is described. The diamine analogs included pyrido[3,4-d]pyrimidine core were reported as tyrosine kinase inhibitors. The chemical reactions of certain unexpected and chemically substantial compounds have been discussed.