Natural Products Research Articles

Anti-colorectal Cancer Activity of Quinazoline Derivatives: A Comprehensive Review

Introduction and Objective: The identification of a bioactive template (or lead) is one of the important features of modern drug discovery. Natural products, synthetic and biotechnological sources, serve as important templates for the development of novel bioactive molecules. Quinazoline is one of the heterocyclic templates present in many natural and synthetic drugs and exhibits various biological activities, including anticancer, by blocking the pharmacological pathway of different targets. Methodology: In this study, the data was collected from the literature and patents to examine the anticolorectal cancer efficacy of quinazoline compounds and their mechanism of actions. According to the published literature and patents, the benzene and/or pyrimidine rings of the quinazoline have been substituted with amino groups or substituted amino groups to develop novel analogues endowed with anticancer properties. The anti-colorectal cancer activity of quinazolines was due to the flexible chain containing terminal phenyl and/or heterocyclic rings (thiazole, pyrazole, piperidine, piperazine, etc.). Results: These quinazoline derivatives were found to inhibit the growth of colorectal cancer cells by modulating the expression of specific genes and proteins involved in cancer progression, such as receptor tyrosine kinases, epidermal growth factor receptors, dihydrofolate reductase, topoisomerases, histone deacetylase, and apoptotic proteins. Conclusion: These findings suggest that the quinazoline nucleus may be exploited to identify new anticolorectal cancer agents with suitable pharmacokinetic profiles.

Natural product synthesis by a nanoporous In-MOF Catalyst: Crystallographic insight by incorporating substrate inside its nanopores

Metal-organic frameworks (MOFs) are promising candidates as nanoporous heterogeneous catalysts over other solid catalysts. Herein, utilizing a new tetra-acid ligand and employing high-valent Indium metal source we have strategically developed a 3D robust nanoporous framework, IITKGP-53, which retained its crystallinity over a wide range of pH solution (2–12). Considering the green synthesis approach IITKGP-53 was explored as a heterogeneous catalyst toward one-pot three-component Strecker reaction under solvent-free condition, with low catalyst loading for a broad range of substrates. Considering practical utility, biologically important natural product, Girgensohnine, was synthesized for the first time by using this catalyst with excellent conversion rate. The substrate binding sites inside the nanopores and host–guest interactions were verified crystallographically by obtaining a substrate inside nanopores of this MOF (aniline@IITKGP-53) and computational modeling. An in-depth theoretical investigation unveiled the most plausible transition states for the first time. This study inaugurates the usage of nanoporous MOFs as heterogeneous catalysts for natural product synthesis.

Substitution of 2-oxoglutarate alters reaction outcomes of the Pseudomonas savastanoi ethylene-forming enzyme

In seeding plants, biosynthesis of the phytohormone ethylene, which regulates processes including fruit ripening and senescence, is catalyzed by 1-aminocyclopropyl-1-carboxylic acid (ACC) oxidase. The plant pathogen Pseudomonas savastanoi (previously classified as: P. syringae) employs a different type of ethylene-forming enzyme (psEFE), though from the same structural superfamily as ACC oxidase, to catalyze ethylene formation from 2-oxoglutarate (2OG) in an arginine dependent manner. psEFE also catalyzes the more typical oxidation of arginine to give L-Δ1-pyrroline-5-carboxylate (P5C), a reaction coupled to oxidative decarboxylation of 2OG giving succinate and CO2. We report on the effects of C3 and/or C4 substituted 2OG derivatives on the reaction modes of psEFE. 1H NMR assays, including using the pure shift method, reveal that, within our limits of detection, none of the tested 2OG derivatives is converted to an alkene; some are converted to the corresponding β-hydroxypropionate or succinate derivatives, with only the latter being coupled to arginine oxidation. The NMR results reveal that the nature of 2OG derivatization can affect the outcome of the bifurcating reaction, with some 2OG derivatives exclusively favoring the arginine oxidation pathway. Given that some of the tested 2OG derivatives are natural products, the results are of potential biological relevance. There are also opportunities for therapeutic or biocatalytic regulation of the outcomes of reactions catalyzed by 2OG-dependent oxygenases by the use of 2OG derivatives.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

Nickel‐Catalyzed Regio‐ and Stereoselective Reductive Alkylative Cyclization of 1,6‐Enynes with Alkyl Bromides

A nickel‐catalyzed reductive alkylative cyclization of 1,6‐enynes with alkyl bromides has been developed. This transformation avoids the use of stoichiometric organometallic reagents and introduces alkyl groups regio‐ and stereoselectively into the products. This method provides a platform for the synthesis of carbo‐ and heterocycles that are widely found in many natural products and biologically active molecules.

Constituents from Dendrobium aphyllum: Bibenzyls, furfurals, phenanthrenes, and phenylpropanoids and their antioxidant and anti-inflammatory potentials

Chemical investigation on the aqueous extract of Dendrobium aphyllum led to the isolation of thirty-one constituents with structures identified by analysis of the extensive spectroscopic data (1D/2D NMR, MS, UV, and ECD), including previously undescribed two bibenzyls, one furfural, and one phenolic acid, namely trigonopol D (1), trigonopol C (2), dendrofunan A (10), and 6-(4-hydroxy-3-methoxyphenyl)-3,6-dioxohexyl acetate (30), respectively, as well as twenty-seven known ones. Among them, there were one new natural product (11), seven compounds (6–7, 9, 12, 20, 28, 31) described from the genus Dendrobium for the first time, and fifteen compounds (8, 13–17, 19, 21–27, 29) isolated from D. aphyllum for the first time. Further, the antioxidant and anti-inflammatory potentials of fifteen compounds (4–5, 8, 11–12, 14–19, 22, 24, 26, and 29) with significant scavenging capacities against DPPH and hydroxyl radicals, and virtual docking activities inhibiting COX-2 and 5-LOX, respectively. Our study may draw the attention of medicinal plant taxonomists and supply potential quality markers for discrimination of D. aphyllum from other species in Dendrobium genus.

Exploitation of ninhydrin core towards spiropyranocoumarin and benzofuranyl coumarin: Synthesis, crystal structure and self-assembly

Pyrano and furanocoumarins are oxygen-containing heterocycles frequently found in natural products and biologically active molecules. In the present work, ninhydrin core is employed for the first time as the pivotal framework to construct benzopyrano/furano coumarin skeleton. It has been found that substrates like phenol, p-/m-cresol, m-methoxyphenol, p-chlorophenol etc. reacted with ninhydrin-4-hydroxycoumarin adduct 3 in AcOH/H2SO4 to furnish a new class of spiropyranocoumarins 5a-f via condensation/cyclization sequence. Under similar conditions, reaction of adduct 3 with 3,5-dihydroxybenzoic acid delivered benzofuranyl coumarin 6 through ring closing/ring opening mechanism. Structures of the synthesized compounds were characterized by IR, 1H and 13C NMR spectroscopy. Single crystal X-ray diffraction study revealed that spiropyranocoumarin 5b self-assembled to form sheet-like arrangement. However, benzofuranyl coumarin 6 was found to display helix-like architecture in the crystalline state. Scanning electron microscopy (SEM) images of compound 5b exhibited flat fibrillar morphology, whereas compound 6 revealed formation of vesicular structure. These types of small heterocyclic molecules are decent candidates for producing promising soft materials.

Analyzing noncovalent interactions between notoginseng saponins and lysozyme by deposition scanning intensity fading MALDI-TOF mass spectrometry.

Analysis of noncovalent interactions between natural products and proteins is important for rapid screening of active ingredients and understanding their pharmacological activities. In this work, the intensity fading MALDI-TOF mass spectrometry (IF-MALDI-MS) method with improved reproducibility was implemented to investigate the binding interactions between saponins from Panax notoginseng and lysozyme. The benchmark IF-MALDI-MS experiment was established using N,N',N″-triacetylchitotriose-lysozyme as a model system. The reproducibility of ion intensities in IF-MALDI-MS was improved by scanning the whole sample deposition with a focused laser beam. The relative standard deviation (RSD) of deposition scanning IF-MALDI-MS is 5.7%. Similar decay trends of the relative intensities of notoginseng saponins against increasing amounts of lysozyme were observed for all six notoginseng saponins. The half-maximal fading concentration (FC50) was calculated to quantitatively characterize the binding affinity of each ligand based on the decay curve. According to the FC50 values obtained, the binding affinities of the six notoginseng saponins were evaluated in the following order: notoginsenoside S > notoginsenoside Fc > ginsenoside Rb1 > ginsenoside Rd > notoginsenoside Ft1 > ginsenoside Rg1. The binding order was in accordance with molecular docking studies, which showed hydrogen bonding might play a key role in stabilizing the binding interaction. Our results demonstrated that deposition scanning IF-MALDI-MS can provide valuable information on the noncovalent interactions between ligands and proteins.

Inflammation in Atherosclerosis: Therapeutic Approaches with Natural Products and Conventional Drugs

Inflammation in Atherosclerosis: Therapeutic Approaches with Natural Products and Conventional Drugs

Multifunctional skin dressings synthesized via one‐pot photopolymerization: Advancing wound healing and infection prevention strategies

AbstractIn the field of wound healing treatment, the development of new materials is essential to cover multiple functions, such as acceleration of the healing process, prevention of infection and response to stimuli, especially if they present lower costs or are easier to manufacture. These properties are of great importance to prompt skin cicatrization. In this work, new multifunctional skin dressings for wound healing and infection prevention are developed based on new hydrogel materials. The dressings are produced via a straightforward and environmentally friendly one‐pot photopolymerization manufacturing process utilizing vitamin B2 aqueous solutions as sensitizer, and energy‐efficient blue light sources. These dressings exhibit a high swelling capacity, pH and temperature responsiveness, biocompatibility, antimicrobial activity in the absence of conventional antibiotics, and are capable of promoting wound healing. The formulation is based on the combination of three monomers: 2‐((methacryloyloxy)ethyl)trimethylammonium chloride, methacrylic acid and N‐vinyl caprolactam. Collagen, hyaluronic acid, and essential oil of hop are added to enhance antimicrobial properties and stimulate regenerative cellular processes. In vivo experiments have demonstrated that pristine dressings are superior in promoting collagen and fibroblast regeneration and accelerating cicatrization as compared to dressings containing natural products. The dressing embedded with hop also displayed antimicrobial characteristics. The preparation and testing of these new efficient wound dressings are described. This study is distinctive in its integration of environmentally conscious manufacturing techniques with innovative material formulations, resulting in superior wound dressings that are both cost‐effective and highly functional. By achieving enhanced healing and infection prevention without the employment of conventional antibiotics, this work represents a substantial advancement in sustainable and effective wound care management.

From nature to medicine: bioactive compounds in the battle against SARS-CoV-2

The COVID-19 pandemic has driven the search for new therapeutic agents against SARS-CoV-2. Natural products have shown promise as sources of bioactive compounds with antiviral properties. This letter highlights the potential of these compounds in developing effective COVID-19 therapies. Quercetin, found in fruits and vegetables, has demonstrated antiviral activity by inhibiting viral replication. Glycyrrhizin, from licorice root, can modulate host cell signaling to inhibit SARS-CoV-2 replication. Curcumin, from turmeric, disrupts the interaction between the virus’s spike protein and the ACE2 receptor, preventing viral entry. Additionally, compounds like resveratrol possess immunomodulatory properties that can reduce the hyperinflammatory response in severe COVID-19. Despite these promising findings, the variability of natural extracts and potential side effects necessitate rigorous clinical trials. Natural product-derived bioactive compounds represent a promising avenue for novel COVID-19 therapies, warranting further investigation and clinical validation to uncover effective treatments and enhance preparedness for future outbreaks.

Anthelmintic activity of three selected ethnobotanical plant extracts against Strongyloides venezuelensis

The agropastoral farmers have employed Turraea vogelii (TVL), Senna podocarpa (SPL), and Jaundea pinnata (JPL) leaves for treating various diseases, including intestinal parasites in livestock and the human population in Nigeria. Gastrointestinal nematodes are highly significant to livestock production and people’s health, and natural products are interesting as sources of new drugs. In this study, we evaluated the effectiveness of extracts derived from these plants in treating parasitic infections using third-stage infective larvae (L3) of Strongyloides venezuelensis. We obtained crude extracts using n-gexane (Hex), ethyl acetate (Ea), and methanol (Met). The extracts were analyzed for their phytochemical composition, and their ability to prevent hemolysis were tested. The mean concentrations of total phenols in SPL Hex, SPL Ea, and SPL Met were 92.3±0.3, 103.0±0.4, and 128.2±0.5 mg/100 g, respectively. Total tannin concentrations for JPL Ea, SPL Ea, SPL Hex, and TVL Hex were 60.3±0.1, 89.2±0.2, 80.0±0.1, and 66.6±0.3 mg/100 g, respectively. The mean lethal concentration (LC50) at 72 h for JPL Ea 39 (26–61) μg/mL. SPL Ea was 39 (34–45) μg/mL, and TVL Hex 31 (26–36) μg/mL. The antiparasitic activities of the extracts against L3 were dose- and time-dependent. All the extracts were slightly hemolytic to the erythrocytes. In this study, the plant extract tested demonstrated significant anti-S. venezuelensis activity. These phytobotanical extracts could be used to create formulations for the potential treatment of helminthiasis in animals and humans.

Enhancing content and decreasing production costs of phycocyanin through phytohormone supplementation in Spirulina cultivations

This study explores the potential of fractional supplementation of the phytohormone indole-3-acetic acid (IAA) to enhance phycocyanin production in Spirulina cultures. Microalgae cultures were supplemented with IAA at specific time points (days 0, 5, 10, 15, 20, and 25), reaching the same supplementation concentration (0.1 mg L−1) in the final 30-day cultivation period. The continuous daily supplementation resulted in a remarkable 229 % (106.41 mg g−1) increase in phycocyanin concentration and a 251 % (8.3 mg L−1 d−1) improvement in productivity compared to the control group without phytohormone addition (32.30 mg g−1 and 2.4 mg L−1 d−1, respectively). Additionally, the strategy successfully reduced the production cost of the pigment by 71 %. This approach can potentially make microalgae-based products more accessible to the population while addressing the industry's need for cost-effective pigment production. The study offers a novel strategy for optimizing natural pigment production and microalgae cultivation.

Evaluation of the combined influence of geological layer property and in-situ stresses on fracture height growth for layered formations

Fracture geometry is important when stimulating low-permeability reservoirs for natural gas or oil production. The geological layer (GL) properties and contrasts in in-situ stress are the two most important parameters for determination of the vertical fracture growth extent and containment in layered rocks. However, the method for assessing the cumulative impact on growth in height remains ambiguous. In this research, a 3D model based on the cohesive zone method is used to simulate the evolution of hydraulic fracture (HF) height in layered reservoirs. The model incorporates fluid flow and elastic deformation, considering the friction between the contacting fracture surfaces and the interaction between fracture components. First, an analytical solution that was readily available was used to validate the model. Afterwards, a quantitative analysis was performed on the combined impacts of the layer interface strength, coefficient of interlayer stress difference, and coefficient of vertical stress difference. The results indicate that the observed fracture height geometries can be categorized into three distinct regions within the parametric space: blunted fracture, crossed fracture, and T-shaped fracture. Furthermore, the results explained the formation mechanism of the low fracture height in the deep shale reservoir of the Sichuan Basin, China, as well as the distinction between fracture network patterns in mid-depth and deep shale reservoirs.

Salmon hatchery strays can demographically boost wild populations at the cost of diversity: quantitative genetic modelling of Alaska pink salmon

Hatcheries are vital to many salmon fisheries, with inherent risks and rewards. While hatcheries can increase the returns of adult fish, the demographic and evolutionary consequences for natural populations interacting with hatchery fish on spawning grounds remain unclear. This study examined the impacts of stray hatchery-origin pink salmon on natural population productivity and resilience. We explored temporal assortative mating dynamics using a quantitative genetic model that assumed the only difference between hatchery- and natural-origin adults was their return timing to natural spawning grounds. This model was parameterized with empirical data from an intensive multi-generational study of hatchery–wild interactions in the world’s largest pink salmon fisheries enhancement program located in Prince William Sound, Alaska. Across scenarios of increasing hatchery fish presence on spawning grounds, our findings underscore a trade-off between demographic enhancement and preservation of natural population diversity. While enhancement bolstered natural population sizes towards local carrying capacities, hatchery introgression reduced variation in adult return timing by up to 20%. Results indicated that hatchery-origin alleles can rapidly assimilate into natural populations, despite the reduced fitness of hatchery fish attributable to phenotypic mismatches. These findings elucidate the potential for long-term demographic and evolutionary consequences arising from specific hatchery–wild interactions, emphasizing the need for management strategies that balance demographic enhancement with the conservation of natural diversity.

Antibacterial, antidiabetic and antioxidant bioevaluation of Calamus leptospadix Griff. and isolation of a flavan type compound

The plant based natural products have always been a rich source of bioactive molecules for drug discovery. The tender shoots of Calamus leptospadix Griff., an edible medicinal plant was extracted using methanol, water and ethanol as three different solvents to study the effect of the extracting solvents and temperature on their antioxidant, antidiabetic and antibacterial properties and total phenolic and flavonoid contents. The antioxidant properties were determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assay. The α-glucosidase inhibitory assay was carried out to determine the antidiabetic potential. The antibacterial properties of the extracts were determined against four strains of bacterial species viz. Bacillus subtilis, Streptococcus pneumoniae, Escherichia coli and Citrobacter freundii using Broth macro dilution method.The methanolic extracts of the plant were found to possess the highest total phenolic and total flavonoid contents. In the antioxidant assays, the cold methanolic extract was found to exhibit the highest DDPH radical scavenging activity and ferric-reducing antioxidant power. In the antidiabetic assay, the extract exhibited better α-glucosidase inhibitory potential than that of the positive control acarbose. It was also found to be effective against both gram-positive and gram-negative strains in the antibacterial assay. A flavan-type compound 4-(5,7-dimethoxychroman-2-yl)phenol was isolated from the most bioactive cold methanolic extract of the plant and characterised from its XRD, 1H- and 13C-NMR, HRMS and IR data.

Hovedulcates A and B, 2,3-dihydrobenzofuran derivatives isolated from the fruits of Hovenia dulcis Thunb. as potential inhibitors of PTP1B and α-glucosidase

From the fruits of Hovenia dulcis Thunb., two new 2,3-dihydrobenzofuran derivatives, named hovedulcates A and B (14 and 16), as well as 20 known compounds (1–13, 15, and 17–22) were isolated. The structures of the isolated compounds were elucidated through a combination of NMR, HR-MS, and ECD spectroscopy analyses, and reported data in the literature. The inhibitory activities of the isolated compounds (1–22) against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase were assessed. Notably, new compounds 14 and 16 exhibited potent inhibitions of both PTP1B and α-glucosidase. The enzyme kinetics analysis was conducted to understand the inhibition mode and inhibitory constants of compounds 14 and 16 for the inhibition of PTP1B and α-glucosidase. Additionally, molecular docking simulations revealed the binding mechanisms and interactions of these compounds with the target enzymes. Our findings suggest that secondary metabolites from H. dulcis fruits are promising natural product treatments for type 2 diabetes.

Amlou inspired spread: Formulation and characterization of new spread based on Ziziphus lotus L. fruit, argan oil, and honey

This study explores novel applications of combining natural products by integrating Ziziphus lotus L. (Z. lotus), honey, and argan oil to create a product similar to traditional Moroccan Amlou (a mixture of almonds, honey, and argan oil). Five formulations were developed with varying percentages of these three ingredients, alongside two formulations of traditional Amlou. The nutritional value, mineral composition, fatty acid profile, bioactive compounds, and antioxidant activities of the products were analyzed using standard analytical methods such as gas chromatography and spectrophotometry. Additionally, sensory evaluations were conducted to assess consumer preferences. The results showed that the new formulations are rich in oil (45.15–52.24 g/100 g), carbohydrates (40.26–46.81 g/100 g), and protein (3.15–3.92 g/100 g). Mineral analysis revealed significant amounts of potassium (443–578 mg/100 g), calcium (98–124 mg/100 g), phosphorus (50–65 mg/100 g), and magnesium (38–50 mg/100 g). The Z. lotus-based products exhibited higher phenolic content (7–12 mg GAE/g), flavonoids (7.10–10.18 mg QE/g), and stronger antioxidant activities using DPPH radical scavenging activity (3.55–11.14 mg AAE/g) and FRAP (5.39–8.55 mg AAE/g). Moreover, the new product retains the beneficial fatty acid profile of argan oil, with a high content of oleic acid (48 %) and linoleic acid (32 %). Sensory evaluation indicated that the formulation consisting of 45 % Z. lotus powder, 50 % argan oil, and 5 % honey was the most appreciated for taste and texture. These findings suggest that incorporating Z. lotus into traditional Amlou recipes not only enhances nutritional and antioxidant properties but also meets consumer acceptance in terms of flavor and texture.

Identification of kibdelomycin and related biosynthetic gene clusters and characterization of the C‐branching of amycolose

Many bacterial natural products contain C‐branched sugars, including components from the outer cell wall or antibiotically active metabolites. The enzymatic C‐branching of keto sugars leading to longer side chains (≥C2), is catalyzed by thiamine diphosphate (ThDP)‐dependent enzymes. Chiral tertiary α‐hydroxy ketones are formed in this process. The ThDP enzymes that catalyze C‐branching reactions belong to one of three enzymatic superfamilies: decarboxy­lases, transketolases, and α‐ketoacid dehydrogenases 2, but branching of keto sugars has only been demonstrated for decarboxylases. In this study, we showed that an α‐ketoacid dehydrogenase is responsible for C‐branching of the deoxyketo sugar amycolose in the biosynthesis of kibdelomycin in Kibdelosporangium sp. MA7385. In addition, we characterized an amino transferase in the same biosynthetic gene cluster (BGC) that accepts a sterically demanding tertiary α‐hydroxy ketone in a downstream reaction. Subsequently, we identified approximately 400 similar BGCs in silico, suggesting that there is a large diversity of possible ThDP‐dependent enzymes catalyzing the C‐branching of keto sugars and subsequent modifications.

Atroposelective total synthesis of strecintide 839

The first total synthesis of the recently isolated strecintide 839 is reported. Strecintide 839 is one of the RiPP natural products that have been vigorously isolated in recent years and is known to possess the extremely rare and highly strained atrop-Trp-Trp linkage. This study details the comprehensive investigation into the construction of the highly strained atrop-Trp-Trp linkage and its application in the total synthesis of strecintide 839.