Potential Biological Activity Research Articles

Synthesis of pyrazole and 1,3,4-oxadiazole derivatives of pharmaceutical potential

Heterocyclic compounds are important molecules that serve as scaffolds or linkers for the core structure of numerous drug substances. In particular, pyrazole and 1,3,4-oxadiazole are compounds of great interest due to their comprehensive biological activities and interesting structural features. Here, we described an efficient and economical synthetic route leading to N-phenyl substituted pyrazole and 1,3,4-oxadiazole derivatives. Retrosynthetic disconnective analysis showed that the N-phenyl substituted pyrazole can be obtained from chalcone, accessible from the respective aldehyde, and acetophenone. The disubstituted 1,3,4-oxadiazole can be constructed from the respective aldehyde, which originates from pyrrole-containing compound, and formyl chloride. Based on our retrosynthetic analysis, N-phenyl substituted pyrazole was obtained by cyclization of the respective chalcone with phenylhydrazine to give pyrazoline which was in turn converted into pyrazole by oxidative aromatization. Potassium carbonate and a catalytic amount of molecular iodine were used to oxidatively cyclize semicarbazones into 1,3,4-oxadiazoles in a transition metal-free process. Novel pyrazole and 1,3,4-oxadiazoles with potential biological activity are investigated as antituberculosis, anticonvulsant, antidiabetic, anticancer, and tyrosinase inhibitory agents.

Exploring the Multifaceted Biological Activities of Anthocyanins Isolated from Two Andean Berries.

Natural pigments extracted from plant species are used in foods, cosmetics, and pharmaceuticals. This study evaluates the comprehensive biological activities of anthocyanins isolated from Andean blueberry (Vaccinium floribundum Kunth) and Andean blackberry (Rubus glaucus Benth), focusing on their antimicrobial, antioxidant, antitumoral, anti-inflammatory, and hemolytic properties. Chemical characterization revealed significant anthocyanin content with complex mass spectrometric profiles indicating diverse glycosylation patterns that may influence their bioactivity. The antimicrobial assays showed that the extracts were particularly effective against Gram-positive bacteria, with minimal inhibitory concentrations (MICs) as low as 1 mg/mL for Rubus glaucus, indicating strong potential for therapeutic use. The antioxidant capacity of the berries was substantial, albeit slightly lower than that of ascorbic acid. The extracts also exhibited notable antitumoral activity in various cancer cell lines, showing promise as adjunctive or preventive treatments. The anti-inflammatory effects were confirmed by inhibiting nitric oxide production in macrophage cells, highlighting their potential in managing inflammatory diseases. In terms of hemolytic activity, Rubus glaucus exhibited dose-dependent effects, potentially attributable to anthocyanins and phenolics, while Vaccinium floribundum demonstrated no significant hemolytic activity, underscoring its safety. These findings suggest that anthocyanins from Andean berries possess potent biological activities, which could be leveraged for health benefits in pharmaceutical and nutraceutical applications. Further studies are needed to isolate specific bioactive compounds and investigate their synergistic effects in clinical and real-world contexts.

Design, synthesis, and characterization of a novel pH-responsive azo dye incorporating a 1,3,4-thiadiazole ring for advanced textile applications

This study presents the synthesis and comprehensive characterization of a novel azo dye derived from 2-(5-amino-1,3,4-thiadiazol-2-yl) phenol (1a). The synthesis was initiated by reacting salicylic acid with thiosemicarbazide in the presence of phosphorus oxychloride (POCl3), yielding an 89 % conversion to compound 1a. The subsequent diazotization and coupling of 1a under alkaline conditions led to the formation of the azo dye (1b). Structural elucidation was confirmed through Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The incorporation of the 1,3,4-thiadiazole ring is significant due to its known influence on enhancing dye stability, reactivity, and potential biological activities, while the salicylic acid moiety contributes to the dye's pH responsiveness. A notable pH-dependent color transition from yellow (pH < 6.0) to red (pH > 8.0) was observed, driven by protonation-induced resonance changes. Computational studies, including Frontier Molecular Orbital (FMO) analysis, revealed a Highest Occupied Molecular Orbital (HOMO)-Lowest Unoccupied Molecular Orbital (LUMO) gap of 1.94 eV, indicating efficient electronic transitions critical for its color properties. Molecular Electrostatic Potential (MEP) and Fukui function analyses provided further insights into the dye's reactivity and potential applications. The dyeing properties were rigorously assessed through K/S values, CIELAB color space, and fastness properties on cotton fabric, demonstrating varied color depths and hues influenced by different mordants, with copper and manganese significantly enhancing color intensity. Colorfastness tests revealed good to fair durability, with untreated fabrics showing optimal performance. This thorough characterization underscores the promising potential of this newly synthesized azo dye for applications in pH-responsive textiles and functional materials, highlighting its relevance for advanced textile and material science applications.

A time and temperature dependent biosynthesis of silver nanoparticles using the extract of Platycladus orientalis’ fruit

Silver nanoparticles (AgNPs) have gained notable/ huge attention, particularly in the biomedical and antibacterial fields, owing to their distinctive characteristics. Biological synthesis of AgNPs is a prominent method due to its ease of preparation, eco-friendliness, non-toxicity and time efficiency. Herein, AgNPs were synthesized using an extract from "Platycladus orientalis" and their antimicrobial and biological properties were thoroughly investigated. The scaling down of Ag⁺ to Ag⁰ was evident through the appearance of a yellow brownish colour. AgNPs were characterized by UV–Visible spectrum, X-ray diffraction (XRD), and scanning electron microscopy (SEM). UV–Visible spectroscopy revealed absorption peaks at around 440 nm for AgNPs synthesized from fruits’ seat coat of Platycladus orientalis. TEM analysis indicates the average size of AgNPs is approximately 50 nm. Powder XRD confirmed the crystalline nature of the AgNPs, with prominent peaks corresponding to face-centred cubic structures. FTIR analysis identified key functional groups involved in the synthesis process. SEM images displayed agglomerated AgNPs with varying diameters and particle dispersion. Molecular docking results showed favourable binding interactions of AgNPs with the protein 2BTD, with a docking score of -3342 kcal/mol, indicating potential biological activity. These findings highlight the effective synthesis of AgNPs using Platycladus orientalis and their significant potential for biomedical applications.

Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects.

The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.

A Green Chemistry Principle for the Biotransformation of Fungal Biomass Derived Chitosan Into Versatile Nano Scale Materials with High Biocompatibility and Potential Biological Activities—A Review

A Green Chemistry Principle for the Biotransformation of Fungal Biomass Derived Chitosan Into Versatile Nano Scale Materials with High Biocompatibility and Potential Biological Activities—A Review

Novel diaryl dihydropyrimidines as promising anticancer agents: In silico, in vitro investigation

Due to the structural resemblance with the nucleic acid bases, Dihydropyrimidines (DHPs) gained a special attention for exploring for chemotherapeutic agents. Diaryl dihydropyrimidines (DADPs) were reported to have anticancer properties and antiviral and antibacterial activities. In an attempt to design new DADP compounds, we have come up with some novel compounds (3a–3o, 4a–4o, 5a–5o) by incorporating the piperonal to check its significance on biological activity. Initially, computational screening has been performed to shortlist the top molecules which are showing better binding interactions with the selected targets of cancer treatment such as VEGFR2, JAK1 kinase, and JAK3 kinase. Later the selected compounds were synthesized (15 compounds) and characterized by spectral analysis. In the in vitro anti-proliferative activity in the three cell lines, it was observed that the compounds have exhibited potential biological activity (IC50 values 3d – 42.67 ± 2.28 μM against MCF-7; 3n – 59.68 ± 2.81 μM against Hep G-7; 3d – 70.64 ± 3.12 μM against A-549). It was observed that the piperonal, substituted phenyl ring, secondary amine in mannich base has resulted with improved biological activity, the same has been observed in molecular docking studies.

Chemical Modifications on the αvβ6 Intergrin Targeting A20FMDV2 Peptide: A review.

Integrin proteins have received a significant increase in attention in recent scientific endeavors. The current trend uses the pre-established knowledge that the arginyl-glycyl-aspartic acid (RGD) structural motif present in the A20FMDV2 peptide is highly selective for the integrin class αvβ6 which is overexpressed in many cancer types. This review will provide an extensive overview of the existing literature research to date to the best of our knowledge, highlighting significant improvements and drawbacks of structure-activity relationships (SAR) work undertaken, aiding future research to identify established SAR for a rational design of future A20FMDV2 mimetic inhibitors. Herein, the review aims to collate the existing structural chemical modifications present on A20FMDV2 in the literature to highlight key structural analogues that display more potent biological activity.

Recent updates on diet‐derived gut microbial metabolites

AbstractEmerging evidence indicates that the health‐beneficial effects of ingested food components depend on in part, their upper and lower gastrointestinal uptake and metabolism and the gut microbial composition of the host. Several dietary components, such as polyphenols, are poorly absorbed in the upper intestinal compartments and extensively metabolized by the colonic microbiota resulting in the production of an array of metabolites. These microbiota‐mediated products possess specific solubility, reactivity, bioavailability, and biological activities. However, identifying and characterizing a wide range of metabolites is challenging due to the high chemical diversity of dietary components and interindividual variability of the gut microbiota. It is, therefore, critical to design an animal model that effectively mimics human microbial metabolism and use multidisciplinary omics approaches such as metabolomics to detect and identify a wide range of metabolites. Here, we provide the current state of knowledge of major diet‐derived gut microbial metabolites and their potential biological activities.

Isolation and In Vitro Biological Evaluation of Triterpenes from Salacia grandifolia Leaves.

Salacia grandifolia is naturally found in the Atlantic Forest regions of Brazil. Despite the pharmacological potential of plants from the Salacia genus, phytochemical studies on this species have not been reported in literature. A new triterpene, 28-hydroxyfriedelane-3,15-dione (1), and seven known compounds (friedelan-3-one (2), friedelan-3β-ol (3), friedelane-3,15-dione (4), 15α-hydroxyfriedelan-3-one (5), 28-hydroxyfriedelan-3-one (6), 30-hydroxyfriedelan-3-one (7), and 29-hydroxyfriedelan-3-one (8)) were obtained from the hexane extract of Salacia grandifolia leaves. These isolated compounds and three extracts, hexane (EH), chloroform (EC), and ethyl acetate (EAE), were assessed for their potential biological activities, which consisted in the evaluation of antiviral activity against a murine coronavirus, mouse hepatitis virus 3 (MHV-3), antibacterial activity against the susceptible and methicillin-resistant Staphylococcus aureus (MRSA), and antileukemia activity against the THP-1 and K-562 cell lines. The extracts EH and EAE along with the triterpenes 1 and 6 exhibited moderate to high antiviral activity, with emphasis on 6, which presented an EC50 value of 2.9 ± 0.3 μM. None of the compounds presented antibacterial activity against the tested strains. The evaluated compounds 1, 4, 6 and 7 exhibited low cytotoxic activity against the tested leukemia cell lines. Taken together, this study comprises an overview for the potential of the Salacia grandifolia biological activities, including a new isolated triterpene.

New Dephenylated Analogues of (–)-Goniofufurone: Optimization of Synthesis from l-Xylose

AbstractNatural products containing highly oxygenated furanofuranone fragments are known for their potent biological activity, but also for their challenging total synthesis. In this study, the synthesis of five novel dephenylated (–)-goniofufurone analogues was completed and their cytotoxic activity against eight malignant and one normal human cell line was evaluated. Compared with previous syntheses of similar analogues, the synthesis was carried out starting from l-xylose, resulting in improved yields and a reduced number of synthetic steps for three divergent intermediates.

Recent Discovery of Nitrogen Heterocycles from Marine-Derived Aspergillus Species.

Nitrogen heterocycles have drawn considerable attention because of their structurally novel and significant biological activities. Marine-derived fungi, especially the Aspergillus species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This review prioritizes the structural diversity and biological activities of nitrogen heterocycles that are produced by marine-derived Aspergillus species from January 2019 to January 2024, and their relevant biological activities. A total of 306 new nitrogen heterocycles, including seven major categories-indole alkaloids, diketopiperazine alkaloids, quinazoline alkaloids, isoquinoline alkaloids pyrrolidine alkaloids, cyclopeptide alkaloids, and other heterocyclic alkaloids-are presented in this review. Among these nitrogen heterocycles, 52 compounds had novel skeleton structures. Remarkably, 103 compounds showed various biological activities, such as cytotoxic, antimicrobial, anti-inflammatory, antifungal, anti-virus, and enzyme-inhibitory activities, and 21 compounds showed potent activities. This paper will guide further investigations into the structural diversity and biological activities of nitrogen heterocycles derived from the Aspergillus species and their potential contributions to the future development of new natural drug products in the medicinal and agricultural fields.

Azidoindolines—From Synthesis to Application: A Review

Azide-containing compounds, organic azides, showcases a variety of reactivities, making them highly convenient and chameleonic intermediates. An indoline derivative has been proven to be of great significance in drug discovery due to its sp3-rich property. In this context, it is interesting to perform such vigorous azidation on medicinal-relevant indoles/indolines, resulting in the production of sp3-rich azidoindolines. The potential biological activity, in combination with the sp3-rich indoline bearing the azido moiety, makes azidoindolines an attractive synthetic target for medicinal and synthetic chemists. This review describes recent advances in the synthesis and application of azidoindolines: (1) iodine-mediated azidations, (2) metal-catalyzed azidations, (3) electrochemical azidations, (4) photochemical azidations, (5) azidation using a combination of an oxidant and an azide source, and (6) nucleophilic azidation.

Hydroethanolic extracts from Bauhinia guianensis: a study on acute toxicity in Zebrafish embryos and adults

Context The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes. Objective The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations. Materials and methods Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h. Results HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg. Conclusions The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.

Hydroxytyrosol isolation, comparison of synthetic routes and potential biological activities.

Hydroxytyrosol (HT) is a polyphenol found in the olive plant (Olea europaea) that has garnered attention from the food, feed, supplement, and pharmaceutical industries. HT has evolved from basic separation and extraction to chemical and biocatalytic synthesis. The yield of HT can reach 1.93 g/L/h through chemical synthesis and 7.7 g/L/h through biocatalysis; however, both methods are subject to inherent limitations. Furthermore, the potential health benefits associated with HT have been highlighted, including its ability to act as an antioxidant, reduce inflammation, combat cancer and obesity, and exert antibacterial and antiviral effects. Its neuroprotective effects, skin protection, and wound healing capabilities are also discussed. Given these remarkable biological properties, HT stands out as one of the most extensively investigated natural phenols. This review highlights future methods and pathways for the synthesis of HT, providing insights based on its bioactivity characteristics, health benefits, and potential future applications.

Synthesis of gem-Difluorinated Oxa/Azaspiro[2.4]heptanes via Palladium-Catalyzed Spirocyclopropanation.

A palladium-catalyzed spirocyclopropanation of gem-difluoroalkenes with π-allylpalladium 1,4-dipoles has been successfully developed, which gives a powerful and straightforward synthetic strategy for the construction of novel gem-difluorinated spirocyclic compounds, 6,6-difluoro-5-oxa/azaspiro[2.4]heptanes. The scope of gem-difluoroalkenes can be extended to styrenes, acrylic esters, and acrylamides to realize the installment of various functional groups and different heteroatoms on the spirocyclic skeletons, which could be converted to valuable compounds with potential biological activity. The mechanistic investigations revealed the competition between spirocyclopropanation and β-F elimination of π-allylpalladium zwitterionic intermediates.

GC-MS/MS Analysis and Wound Repair Potential of Urtica dioica Essential Oil: In silico Modeling and In vivo Study in Rats.

The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial. Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study. Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control. The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.

Multicomponent Synthesis of Novel Unsymmetric 6-Aryl Substituted 5-Nitropyridines

We have previously studied a multicomponent reaction for the synthesis of unsymmetrical 5-nitro-1,4-dihydropyridines using unsubstituted 2-nitroacetophenone, 1,3-dicarbonyl compounds, and various aldehydes such as formaldehyde, acetaldehyde, and furfural. This paper reports the use of unsymmetrical 3-acetyl-5-nitro-1,4-dihydropyridines containing aryl substituents at the 6-position in a multicomponent synthesis reaction. The starting aryl-substituted nitroacetophenones were prepared by two methods. The first method involved the two-step Katritzky method, which is described in the literature. This method consists of preparing N-acylbenzotriazoles from the corresponding substituted derivatives of benzoic acid and 1,2,3-benzotriazole in the presence of thionyl chloride. This is followed by C-acylation of nitromethane in supernatron medium (t-BuOK – DMSO). A number of 2-nitroacetophenone derivatives were prepared from more commercially available aromatic aldehydes by the Henry reaction with nitromethane followed by oxidation of the resulting secondary nitroalcohols. The multicomponent reaction of 6-aryl-substituted 5-nitro-1,4-dihydropyridines and their subsequent aromatization into 5-nitropyridines allowed us to reduce the overall reaction time by more than 40 times and to increase the total yield of 5-nitro-6-arylpyridines by an average of twofold compared to the method described in the literature. Furthermore, the 3-acetyl-5-nitropyridines we have obtained are significant intermediates in the synthesis of novel, more complex heterocyclic systems with potential biological activity. These systems include δ-carbolines and epoxybenzooxocyno[4,3-b]pyridines, which are currently of great interest for the study of their properties.

Palladium-Catalyzed Synthesis of 6-aryl Dopamine Derivatives

Dopamine is a key neurotransmitter involved in a series of biologically relevant processes and its derivatives have sparked significant interest as intriguing synthetic targets. This class of compounds is indeed not only considerable for the potential biological activities but is also promising for diverse applications in material science. In light of this, our research was focused on the synthesis of 6-aryldopamine derivatives starting from 4-(2-aminoethyl)phenol through a sequential protocol, whose main steps are hydroxylation, halogenation, and Suzuki cross-coupling. Our method demonstrated versatility, efficiency, and compatibility with various functional groups, including aldehydes, ketones, esters, ethers, and fluorine.

Exploring the potential therapeutic role of benzofuran derivatives in cancer treatment

Benzofuran serves as the primary active pharmaceutical ingredient (API) in a plethora of both naturally occurring and synthetic drugs known for their potent biological activities. The diverse array of biological effects demonstrated by benzofuran and its analogues encompasses anticancer, anti-microbial, anti-inflammatory, anti-fungal, analgesic, anti-parasitic, anti-hyperglycemic, anti-hyperlipidemic, anti-convulsant, antipyretic, anti-tubercular, anti-Alzheimer, and antioxidant properties, among others. Given this extensive range of therapeutic potentials, benzofuran and its derivatives have garnered significant attention and are extensively utilized in pharmaceutical research and development. This review article focuses specifically on the anti-cancer properties of benzofuran and its derivatives, underscoring the pivotal role of benzofuran as a prominent and versatile scaffold for designing and developing novel therapeutic agents.