Natural Products Research Articles

Merancang Bisnis Sampo Alami dari Ekstrak Buah Parijoto melalui Analisis Pasar

The use of synthetic products often causes skin problems such as irritation, itching, allergies and erythema. This causes the use of natural products to become an alternative for dealing with hair problems. In entering the natural cosmetics business, market analysis is required. This research aims to analyze the market so that it can determine consumer interest and market opportunities for natural shampoo from parijoto fruit extract. Market opportunity analysis was carried out using the PAM TAM SAM SOM method, Google Trends analysis, competitor analysis, and descriptive analysis of survey results of 52 potential consumers via Google Form. The results of the analysis show that the product has a very large and profitable opportunity in the market, is superior to several competitors, and the dry/powder form of shampoo is more popular than the liquid shampoo form, 82.7% of respondents are interested in using powder shampoo and 96.2% are interested use natural shampoo.

Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids

Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures.

The catalytic asymmetric polyene cyclization of homofarnesol to ambrox.

Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon-carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors1-3. Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists. In particular, the polyene cyclization of (3E,7E)-homofarnesol to the valuable naturally occurring ambergris odorant (-)-ambrox is recognized as a longstanding challenge in chemical synthesis1,4-7. Here we report a diastereoselective and enantioselective synthesis of (-)-ambrox and the sesquiterpene lactone natural product (+)-sclareolide by a catalytic asymmetric polyene cyclization by using a highly Brønsted-acidic and confined imidodiphosphorimidate catalyst in the presence of fluorinated alcohols. Several experiments, including deuterium-labelling studies, suggest that the reaction predominantly proceeds through a concerted pathway in line with the Stork-Eschenmoser hypothesis8-10. Mechanistic studies show the importance of the enzyme-like microenvironment ofthe imidodiphosphorimidatecatalyst for attaining exceptionally high selectivities, previously thought to be achievable only in enzyme-catalysed polyene cyclizations.

Annulative coupling of α-substituted acrylic acids and sulfoxonium ylides: easy access to bioactive γ-butyrolactones.

We present a straightforward, catalyst- and additive-free method for synthesizing keto γ-butyrolactones using readily available β-keto sulfoxonium ylides and acrylic acids. This robust approach demonstrates exceptional compatibility with various functional groups on β-keto sulfoxonium ylides and α-substituted acrylic acids, resulting in good to high yields of the anticipated products. Moreover, the practicality of this approach was validated through large-scale reactions and the successful conversion of some synthesized derivatives into bioactive natural products, including L-factor, muricatacin, and cytosporanone A.

Bis-benzylisoquinoline alkaloids inhibit African swine fever virus internalization and replication by impairing late endosomal/lysosomal function.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a highly infectious disease afflicting domestic pigs and wild boars. It exhibits an alarming acute infection fatality rate of up to 100%. Regrettably, no commercial vaccines or specific drugs for combating this disease are currently available. This study evaluated the anti-ASFV activities in porcine alveolar macrophages, 3D4/21 cells, and PK-15 cells of four bis-benzylisoquinoline alkaloids (BBAs): cepharanthine (CEP), tetrandrine, fangchinoline, and iso-tetrandrine. Furthermore, we demonstrated that CEP, which exhibited the highest selectivity index (SI = 81.31), alkalized late endosomes/lysosomes, hindered ASFV endosomal transport, disrupted virus uncoating signals, and thereby inhibited ASFV internalization. Additionally, CEP disrupted ASFV DNA synthesis, leading to the inhibition of viral replication. Moreover, berbamine was labeled with NBD to synthesize a fluorescent probe to study the cellular location of these BBAs. By co-staining with Lyso-Tracker and lysosome-associated membrane protein 1, we demonstrated that BBAs target the endolysosomal compartments for the first time. Our data together indicated that BBAs are a class of natural products with significant inhibitory effects against ASFV infection. These findings suggest their potential efficacy as agents for the prevention and control of ASF, offering valuable references for the identification of potential drug targets.IMPORTANCEThe urgency and severity of African swine fever (ASF) underscore the critical need for effective interventions against this highly infectious disease, which poses a grave threat to domestic pigs and wild boars. Our study reveals the potent anti-African swine fever virus (ASFV) efficacy of bis-benzylisoquinoline alkaloids (BBAs), particularly evident in the absence of progeny virus production under a 5 µM concentration treatment. The structural similarity among cepharanthine, tetrandrine, fangchinoline, and iso-tetrandrine, coupled with their analogous inhibitory stages and comparable selectivity indexes, strongly suggests a shared antiviral mechanism within this drug category. Further investigation revealed that BBAs localize to lysosomes and inhibit the internalization and replication of ASFV by disrupting the endosomal/lysosomal function. These collective results have profound implications for ASF prevention and control, suggesting the potential of the investigated agents as prophylactic and therapeutic measures. Furthermore, our study offers crucial insights into identifying drug targets and laying the groundwork for innovative interventions.

Anti-obesity Impact of Natural Products Modulated by Peroxisome Proliferator-Activated Receptor Gamma and CCAAT/Enhancer-Binding Protein-Alpha via Wnt/β-Catenin Signaling Pathway

Anti-obesity Impact of Natural Products Modulated by Peroxisome Proliferator-Activated Receptor Gamma and CCAAT/Enhancer-Binding Protein-Alpha via Wnt/β-Catenin Signaling Pathway

A modular toolkit for environmental Rhodococcus, Gordonia, and Nocardia enables complex metabolic manipulation.

Soil-dwelling Actinomycetes are a diverse and ubiquitous component of the global microbiome but largely lack genetic tools comparable to those available in model species such as Escherichia coli or Pseudomonas putida, posing a fundamental barrier to their characterization and utilization as hosts for biotechnology. To address this, we have developed a modular plasmid assembly framework, along with a series of genetic control elements for the previously genetically intractable Gram-positive environmental isolate Rhodococcus ruber C208, and demonstrate conserved functionality in 11 additional environmental isolates of Rhodococcus, Nocardia, and Gordonia. This toolkit encompasses five Mycobacteriale origins of replication, five broad-host-range antibiotic resistance markers, transcriptional and translational control elements, fluorescent reporters, a tetracycline-inducible system, and a counter-selectable marker. We use this toolkit to interrogate the carotenoid biosynthesis pathway in Rhodococcus erythropolis N9T-4, a weakly carotenogenic environmental isolate and engineer higher pathway flux toward the keto-carotenoid canthaxanthin. This work establishes several new genetic tools for environmental Mycobacteriales and provides a synthetic biology framework to support the design of complex genetic circuits in these species.IMPORTANCESoil-dwelling Actinomycetes, particularly the Mycobacteriales, include both diverse new hosts for sustainable biomanufacturing and emerging opportunistic pathogens. Rhodococcus, Gordonia, and Nocardia are three abundant genera with particularly flexible metabolisms and untapped potential for natural product discovery. Among these, Rhodococcus ruber C208 was shown to degrade polyethylene; Gordonia paraffinivorans can assimilate carbon from solid hydrocarbons; and Nocardia neocaledoniensis (and many other Nocardia spp.) possesses dual isoprenoid biosynthesis pathways. Many species accumulate high levels of carotenoid pigments, indicative of highly active isoprenoid biosynthesis pathways which may be harnessed for fermentation of terpenes and other commodity isoprenoids. Modular genetic toolkits have proven valuable for both fundamental and applied research in model organisms, but such tools are lacking for most Actinomycetes. Our suite of genetic tools and DNA assembly framework were developed for broad functionality and to facilitate rapid prototyping of genetic constructs in these organisms.

Generation of lysolipin derivatives by genetic engineering

Lysolipin I is a halogenated, polycyclic xanthone natural product belonging to the polyketide class of antibiotics, naturally produced by Streptomyces violaceoniger TÜ96 and Streptomyces tendae TÜ4042. The biosynthesis is encoded on a 43 kb-spanning biosynthetic gene cluster. Heterologous expression of the gene cluster has been established in previous work by using the cosmid 4H04, which was transferred to Streptomyces albus. In the current study, we demonstrate the optimization of production yields of therapeutically interesting lysolipin derivatives with extended activity against Gram-negatives and less cytotoxic bioactivities, respectively, by using mutated heterologous S. albus producer strains. Production yields were significantly increased by adapting cultivation conditions as well as by inactivating the transcriptional repressor gene llpRI, which lead to increased and consistent lysolipin (derivatives) production. Furthermore, cultivation of a S. albus 4H04∆llpOI mutant strain in bromide-containing fermentation medium resulted in the production of a new brominated lysolipin derivative (C28H20BrNO9).

Natural products as anticancer agents and enhancing their efficacy by a mechanism-based precision approach

Traditional medicines and their active ingredients and some natural products and derived analogs have been used for treating multiple diseases including cancer. Among these compounds cytotoxic agents such as bleomycin, paclitaxel and vincristine block essential pathways and genes required for cancer cell growth and these agents have diverse clinical applications. Dietary phenolics including flavonoids and related compounds are associated with multiple health benefits however most individual dietary compounds and other natural products that show promising anticancer activity in preclinical studies exhibit minimal clinical effectiveness and this is particularly true for cancer. Many of the compounds perform poorly in clinical trials due to pharmacokinetic consideration and limited uptake (e.g., curcumin) and these are issues that can be addressed. The clinical effectiveness of flavonoids and many other natural product-derived anticancer compounds can also be enhanced by a more targeted approach. This would include identifying a significant response/gene or target in a specific cancer and then identifying the optimal compound. In this review, I have discussed a limited number of targets including non-oncogene addiction genes such as Sp transcription factors, reactive oxygen species (ROS) or the orphan nuclear receptor 4A (NR4A) sub-family. Thus, the most active compound for these responses could be used only for treating patients that are ROS-inducible or highly express targets such as Sp1 or NR4A sub-family members. A mechanism-based precision medicine approach should enhance the clinical efficacy of dietary and related natural products as anticancer agents and decrease toxic side effects for some combination therapies.

READRetro: natural product biosynthesis predicting with retrieval-augmented dual-view retrosynthesis.

Plants, as a sessile organism, produce various secondary metabolites to interact with the environment. These chemicals have fascinated the plant science community because of their ecological significance and notable biological activity. However, predicting the complete biosynthetic pathways from target molecules to metabolic building blocks remains a challenge. Here, we propose retrieval-augmented dual-view retrosynthesis (READRetro) as a practical bio-retrosynthesis tool to predict the biosynthetic pathways of plant natural products. Conventional bio-retrosynthesis models have been limited in their ability to predict biosynthetic pathways for natural products. READRetro was optimized for the prediction of complex metabolic pathways by incorporating cutting-edge deep learning architectures, an ensemble approach, and two retrievers. Evaluation of single- and multi-step retrosynthesis showed that each component of READRetro significantly improved its ability to predict biosynthetic pathways. READRetro was also able to propose the known pathways of secondary metabolites such as monoterpene indole alkaloids and the unknown pathway of menisdaurilide, demonstrating its applicability to real-world bio-retrosynthesis of plant natural products. For researchers interested in the biosynthesis and production of secondary metabolites, a user-friendly website (https://readretro.net) and the open-source code of READRetro have been made available.

Natural active products in fruit postharvest preservation: A review

AbstractAbundantly available plants, animals, and microbes are excellent source of active substance to be used as fruit preservatives to delay postharvest fruit from decay, maintain good quality, and increase the shelf life. Although they are effective and free from toxicological risks, the use of the natural active products in agriculture is still limited due to the high cost of producing, complexity interaction in food matrix, and unacceptance of odor. This review focuses on employing naturally occurring bioactive compounds as an alternative to the synthetic preservatives used in fruit. For this purpose, natural compounds from abundantly available source, such as plants, animals, and microbes, are systematically described for their properties, mechanism of action, and applicability. Different postharvest handling of bioactive compounds and mechanism of their triggered/controlled release properties are discussed, especially with regard to challenge and future directions of these new strategy to preserve fruit in industry. This review offers a fundamental theory and technologies to develop the efficient and safe alternative strategies to synthetic fruits preservatives. Overall, the utilization of natural preservative techniques offers promising opportunities to maintain quality and extend shelf life of fruit, with potential applications in various industries such as vegetables, meat, and processed food.

Palladium-catalyzed γ-C-H Arylation of Unsaturated Carbonyl Compounds: An Emerging Remote Buchwald–Hartwig–Miura Arylation

As an important complement to Buchwald-Hartwig-Miura arylation, Pd-catalyzed -C-H including -C(sp3)-H and -C(sp2)-H arylations provide a more direct way to install an aryl group on less reactive -site of the unsaturated carbonyls, attracting considerable interests from chemistry community in recent years. The review summarizes the applications of this method in both cyclic and linear unsaturated carbonyls (aldehydes, ketones, esters, amide, and nitriles), as well as in the total synthesis of natural products, natural products skeletons, and bioactive analogues.

From natural marine bacteria and fungi to culturable ones: What affects their bioactivity?

Marine bacteria and fungi have been known as sources of drug candidates. Novel natural products discovery derived from marine bacteria and fungi has been boosted in the last decades. This review discusses the challenges of culturing marine bacteria and fungi taken from their natural habitat into laboratory-scale culturable ones. Since, not all bacteria and fungi, when they are taken from their natural habitat and grown in a laboratory setting, are culturable. This review will also discuss possible solutions to overcome those challenges. Targeted bioactivity relies on the marine bacterial and fungal growth, especially due to the capability on producing the intended natural products. From this review, some important factors that must be taken into consideration to have optimal bacterial and fungal growth are genes and their variation in a species, media composition, and growth condition.

Carbohydrate Derived α,β-Unsaturated Enals (Perlin’s Aldehyde) as Chiral Synthon for the Synthesis of Privileged Scaffolds

Perlin’s aldehyde is an α,β-unsaturated carbonyl compound with two well-defined chiral centres and a free hydroxy group. Since its discovery and synthesis by A. S. Perlin in 1975, it has been used as a flexible chiral synthon for synthesising natural products, its scaffolds and biologically significant compounds. Perlin’s aldehydes serve as useful starting materials in diversity-oriented synthesis (DOS) and chiral building blocks in organic synthesis. Currently, synthesising frameworks based on carbohydrates is at the forefront of organic synthesis. Inspired by the reactivity of Perlin’s aldehyde, various research groups worldwide used this molecule as a chiral synthon and published a number of research papers and a review article covering literature until 2012. This review covers recent advances in the synthesis of natural products, their scaffolds and other molecules, starting from perlin aldehyde, covering the literature from 2013 till date.

The Influence of Phytoconstituents for the Management of Antipsoriatic Activity in Various Animal Models.

It is possible for psoriasis to manifest at any point in a person's life, regardless of their age, gender, or geographic location. It is a chronic immune-linked inflammatory skin ill-ness that affects individuals of various racial and ethnic origins. It is recognized to be a long-lasting condition. Because of the significant contribution that natural products have made, there has been a significant advancement in the treatment of skin illnesses such as psoriasis. The biggest number of phytochemicals derived from a wide range of plants and herbs are now being used in a variety of applications throughout the whole world. Additionally, a number of phyto-chemicals, including aloe-emodin, psoralen, curcumin, and others, have been effectively ex-tracted in pure or clear form, and they have shown a great deal of efficacy in the treatment of psoriasis illness. There is evidence that a few herbal remedies are effective, and the occurrence of these phytochemicals provides more proof. When synthetic medications are used for chronic therapy, they may cause a variety of adverse consequences; hence, the exploration of natural pharmaceuticals can give a successful natural treatment with a minimal amount of adverse ef-fects. Within the scope of this concise review, a number of plant sources that possess anti-pso-riatic activity are investigated, and the antipsoriatic effects of these plant sources are shown on a number of animal models using particular pathways.

In vitro effect of Lenzites betulinus mushroom against therapy-induced DNA damage in peripheral blood lymphocytes of patients with acute coronary syndrome

Ethnopharmacological relevanceAcute coronary syndrome (ACS) represents a group of diseases that are the result of reduced blood flow to the heart. There are natural products, based on mushrooms, used traditionally in the treatment of cardiovascular diseases. Aim of the studyAssessment of the potential protective effect of L. betulinus mushroom against therapy-induced DNA damage in lymphocytes of patients with ACS in relation to the phytochemical properties of the mushroom. Materials and methodsThe study included 30 ACS patients and 30 healthy controls. The genotoxic potential of acetone and ethanol extract of L. betulinus was evaluated using the comet assay. The contents of minerals were determined by inductively coupled plasma optical emission spectrometry. Determination of sugars and organic acids was performed using a DIONEX ICS 3000 DP liquid chromatography system. Analysis of fatty acids was performed at Focus GC coupled with PolarisQ mass spectrometer. The total phenolic and flavonoid contents in the mushroom extracts were measured using spectrophotometric methods. The qualitative and quantitative content of polyphenolic compounds was investigated by the UHPLC-DADMS/MS method. ResultsThe comet assay showed that both mushroom extracts did not increase the level of DNA damage in the lymphocytes of healthy individuals, while they significantly decreased the %DNA damage and genetic damage index (p < 0.0005) in the therapy-induced lymphocytes of patients. The mushroom was very rich in phytochemical composition. The results showed that the most abundant components in the mushroom were phosphorus, potassium, sodium, sulfur, and calcium among minerals and glucose, fructose, galactose, sorbitol, and turanose among carbohydrates. Among organic acids were present in higher concentrations malic, citric, and maleic acids, while among fatty acids, the most abundant were trans-linoleic, cis-oleic, palmitic, docosahexaenoic and eicosadienoic acids. The results showed that the highest amount of total phenols and flavonoids in the mushroom extracts were obtained in the acetone extract. The most abundant polyphenolic compounds were chlorogenic acid and quercetin in both extracts of mushroom. ConclusionsThis study indicates that L. betulinus can be considered a mushroom with a high nutritional and functional value. Extracts of the mushroom were not genotoxic in tested concentrations in cultured human lymphocytes of healthy individuals, while in ACS patients they manifested a protective effect against therapy-induced DNA damage. The acetone extract showed a stronger protective effect against therapy-induced DNA damage, which is consistent with its phytochemical composition.

Microbial synthesis of gallic acid and its glucoside β-glucogallin.

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives.

Advances in the Intermolecular Asymmetric Allylic Functionalization of Unreactive Acyclic Alkenes

Allylic C(sp3)−H functionalized architectures are not only widely present in natural products, pharmaceuticals, and functional organic materials, but also serve as versatile building blocks to furnish important functionalized molecules in synthetic chemistry. Accordingly, various strategies to access allylic functionalized alkenes in a stereoselective manner have been developed. However, chemo-, regio- and stereoselective intermolecular asymmetric allylic functionalization (AAF) of unreactive acyclic alkene (UAA) from readily available materials, representing a highly atom- and step-economic approach toward the generation of structural complexity, remains elusive and challenging. Herein, we review all intermolecular asymmetric catalyzed methods, with emphasis on the construction of chiral allylic units by activation of allylic C-H bonds of UAAs. Our analysis serves to document the considerable and rapid progress within the field, while also highlighting the limitations of current methods.

Metabolomic insights into plant-derived cyclolinopeptides as natural therapeutics for management of paroxysmal hypertension: an in-silico approach

Paroxysmal hypertension is a type of response exerted by the body towards external stimulus like physical, mental, or emotional stress which leads to chemical changes in the body that accelerates the physiological parameters like stress hyper-glycemia, obesity, stress cardiomyopathy, hemorrhagic stroke etc. Due to ill effects of chemical drugs administered by the clinicians, there is need of natural anti-depressant products which may serve as an alternative medicine. Compounds like cyclolinopeptides, cyclosporin A, and curcacyclines have exhibited potential immunosuppressive activity. With objective of drug discovery, this study investigates the role of sub-types of cyclolinopeptides as potential drugs against paroxysmal hypertension and predict their mode of action in biochemical pathways and their role in mitigation of stress induced hyper response.

The Mediterranean Species Calendula officinalis and Foeniculum vulgare as Valuable Source of Bioactive Compounds

Research studies on plant secondary metabolites have increased over the last decades as a consequence of the growing consumer demand for natural products in pharmaceutics and therapeutics, as well as in perfumery and cosmetics. In this perspective, many Mediterranean plant species could be an appreciated source of bioactive compounds with pharmacological and health-promoting properties, including antioxidant, antimicrobial, antiviral, anti-inflammatory, and antitumor ones. Calendula officinalis and Foeniculum vulgare are commercially important plants of the Mediterranean flora, with great therapeutic use in the treatment of many disorders since ancient times, and are now listed in several world pharmacopoeias and drug agencies. The present review offers an overview of the main phytochemicals, phenols, terpenes, and alkaloids, biosynthesized in C. officinalis and F. vulgare, both species endemic to the Mediterranean region. Further, all current knowledge and scientific data on taxonomic classification, botanical description, traditional uses, pharmacological studies, and potential toxicity of both species were reported. The principal aim of this review is to point out the prospective use of C. officinalis and F. vulgare as valuable reservoirs of beneficial plant-derived products with interesting biological properties, also providing suggestions and future challenges for the full exploitation of these two Mediterranean species for human life improvement.