Bioactive Products Research Articles

Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.

The problems with current strategies to control canine visceral Leishmaniasis (CVL), which include the euthanasia of infected animals, and also the toxicity of the drugs currently used in human treatments for CVL, add urgency to the search for new therapeutic agents. This study aimed to evaluate the activity against Leishmania (L.) infantum of 12 amides that are chemically inspired by gibbilimbol B, a bioactive natural product that was initially obtained from Piper malacophyllum. Three of these compounds-N-(2-ethylhexyl)-4-chlorobenzamide (9), N-(2-ethylhexyl)-4-nitrobenzamide (10), and N-(2-ethylhexyl)-4-(tert-butyl)benzamide (12) -demonstrated activity against the intracellular amastigotes without toxicity to mammalian host cells (CC50 > 200 μM); compounds 9, 10, and 12 resulted in EC50 values of 12.7, 12.2, and 5.1 μM, respectively. In silico drug-likeness studies predicted that these compounds would show high levels of gastrointestinal absorption, would be able to penetrate the blood-brain barrier, would show moderate solubility, and would not show unwanted molecular interactions. Due to their promising pharmacological profiles, compounds 9 and 10 were selected for mechanism of action studies (MoA). The MoA studies in L. (L.) infantum revealed that neither of the compounds affected the permeabilization of the plasma membrane. Nevertheless, compound 9 induced strong alkalinization of acidocalcisomes, which resulted in a significant and rapid increase in intracellular Ca2+ levels, thereby causing the depolarization of the mitochondrial membrane potential and a reduction in the levels of reactive oxygen species (ROS). In contrast, compound 10 induced a gradual increase in intracellular Ca2+ levels and a similarly gradual reduction in ROS levels, but it caused neither acidocalcisome alkalinization nor mitochondrial membrane potential depolarization. Finally, the MALDI-TOF/MS assessment of protein alterations in L. (L.) infantum treated separately with compounds 9 and 10 revealed changes in mass spectral profiles from both treatments. These results highlight the anti-L. (L.) infantum potential of these amides-especially for compounds 9 and 10-and they suggest that these compounds could be promising candidates for future in vivo studies in VL-models.

Application of the Wittig Rearrangement of N-Butyl-2-benzyloxybenzamides to Synthesis of Phthalide Natural Products and 3-Aryl-3-benzyloxyisoindolinone Anticancer Agents.

Application of the [1,2]-Wittig rearrangement and cyclisation approach to 3-arylphthalides has been evaluated for the synthesis of three bioactive natural products. While this is successful in the case of crycolide, providing the second synthesis of this compound, the more sterically demanding targets isopestacin and cryphonectric acid prove not to be amenable to this approach, with the 2,6-disubstituted aryl groups causing the failure of the rearrangement and alkylation steps, respectively. Direct oxidation of the substituted benzhydrols resulting from [1,2]-Wittig rearrangement using MnO2 provides a new route to 3-aryl-3-hydroxyisoindolinones, and this method has been used in the synthesis of two 3-aryl-3-benzyloxyisoindolinone anticancer agents.

Non-food renewable and bioactive products for pesticides: Synthesis, anti-oomycete and anti-fungal activities of 9R-acyloxyquinine derivatives bearing an 1,3,4-oxadiazole moiety

Quinine is the main alkaloids in the bark of Cinchona and its homologous plants of Rubiaceae. To discover biorational natural product-based pesticides, a series of 9R-acyloxyquinine derivatives containing 1,3,4-oxadiazole moieties were prepared by ingeniously introducing an active ester group and a 1,3,4-oxadiazole five membered heterocyclic ring at its C-9 position, and their structures were well characterized by 1H NMR, 13C NMR, HRMS, and m.p. The stereochemical configuration of target compound 6 t was unambiguously subjected to single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete and anti-fungal agents against two serious agricultural diseases, Phytophthora capsici and Fusarium graminearum we assessed. Among all tested compounds, 1) Compounds 6c and 6d displayed promising anti-oomycete against P. capsici, with EC50 values of 38.42 and 35.49 mg/L, respectively. 2) Compound 6i exhibited promising anti-fungal against F. graminearum, with an EC50 value of 29.92 mg/L. Moreover, some interesting results of structure-activity relationships were also observed. The results of this study pave the way for further design, structural modification, and development of quinine derivatives as plant anti-oomycetes and anti-fungal agents in crop protection.

Phytochemical constituents from root barks of Eleutherococcus henryi Oliv. and their anti-neuroinflammatory effect

Ethnopharmacological relevanceThe cortex of Eleutherococcus henryi (EH, Araliaceae), also known as "Wu-Jia-Pi", is known for its effects such as dispelling wind and dampness, calming the mind and enhancing intelligence, removing heat and toxin, strengthening muscles and bones, and nourishing the liver and kidneys. Throughout Chinese history and tradition, it has been used for conditions like amnesia, mental fatigue, arthritis, hepatitis, and rheumatism. However, research evaluating its neuroprotective effects and pharmacological properties remains scarce. Aim of the studyThe goal is to explore the anti-neuroinflammatory properties of EH in vitro and to discover precisely the bioactive natural products within the medicinal plant that are relevant to its traditional usage. Materials and methodsUtilizing chromatographic techniques, a phytochemical exploration was conducted. The phytochemical structures of the natural products were then elucidated through an analysis involving comprehensive spectra and a comparison with relevant data from published studies. Network pharmacology combined with molecular dynamics simulations (MDs) and docking were applied to forecast potential anti-neuroinflammatory targets of active compounds. In vitro, the anti-neuroinflammatory efficacy was evaluated via the suppression of inflammatory mediators activated by lipopolysaccharide (LPS) in BV2 microglia. ResultsThe methanol extract of E.henryi (EHME) restrained the NO release in LPS-activated BV2 microglia, demonstrating anti-neuroinflammatory activity. Subsequently, chemical composition analysis revealed the separation and elucidation of 31 secondary metabolites, comprising 7 new compounds (1–7) and 1 new natural product (8). Based on LPS-induced BV2 cell in vitro activity tests, compounds 4–17, 19, 20, 22, 23, 26, 29 and 31 were found to exhibit potential anti-neuroinflammatory activity, with compound 6 showing the highest efficacy. Furthermore, employing network pharmacology in conjunction with both molecular docking and MDs, potential anti-neuroinflammatory targets of compound 6 were predicted to include TLR4, Src, MAPK, and NF-κB. Finally, validation through in vitro experiments confirmed that the anti-neuroinflammatory mechanism of compound 6 is associated with the TLR4/Src/MAPK p38/NF-κB p65 signaling pathways. ConclusionsThe study affirmed the traditional efficacy of E. henryi and unveiled novel lignans as potent agents against neuroinflammation.

Catalytic asymmetric inverse-electron-demand Diels–Alder reaction of 2-pyrones with aryl enol ethers

Chiral aryl cyclohex-3-en ether scaffold is widely present in bioactive natural products and drugs. The exploitation of efficient and enantioselective methods for the construction of aryl cyclohex-3-en ether scaffold is significant. Herein we disclose a chiral N,N’-dioxide/Lewis acid complex-catalyzed asymmetric inverse-electron-demand Diels–Alder (IEDDA) reaction using electron-deficient 3-carboalkoxyl-2-pyrones and less electron-enriched aryl enol ethers as reactants. A wide range of non- and 1,2-disubstituted acyclic aryl enol ethers are applicable to deliver diverse chiral bridged bicyclic lactones in high yields and stereoselectivities (up to 95% yield, >20:1 dr, 97:3 er). The bridged bicyclic lactone core can be easily converted into chiral aryl cyclohex-3-en ether scaffold. Notably, DFT calculations revealed a stepwise and endo mechanism to explain the high enantioselectivity controlled by the cooperative effect of the steric factors and the dispersion interactions between ligands and enol ethers.

Effect of malted millet blends with defatted soybean and cinnamon flours on physiochemical and bioactive properties

The study was on physiochemical and bioactive properties of malted millet blends with defatted soybean and cinnamon flour envisaged for porridge use. The proximate composition of the blend decreased with malting addition from millet but increased with soybean flour addition except in ash content. Moisture content ranged between 8.74-9.00%, crude protein 10.08-12.18% crude fiber 1.56-2.25%, ash 3.56-2.02% and crude fat content was 3.00-5.75%, respectively. The functional properties of the flour blends decreased as the inclusion of malted millet increased, but bulk density, swelling capacity, oil and water absorption capacities of the blends used as functional porridge increase with soybeans flour ration inclusion. The antioxidant and anti-diabetes properties of FRAP 0.85-0.47% and α-amylase 32.20-27.47 g/mL increased with millet malt addition but DPPH 44.68-53.66% and metal chelation 23.73-34.40% and α-glycosidase 21.49-34.37 g/mL was high as defatted soybean flour addition increased. Addition of defatted soybean flour on malted millet and cinnamon flour produced a noticeable effect on the sensory color, taste, flavor, texture, crispiness and overall acceptability on the porridge produced. Malted millet addition has less significant effect compared to defatted soybean flour in making functional and bioactive composite flour porridge production from millet malting, defatted soybean and cinnamon spice flour blends.

Molecular Targets of Valeric Acid: A Bioactive Natural Product for Endocrine, Metabolic, and Immunological Disorders.

Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach meaningful a conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

Cooperative Noncovalent Interactions Controlling Amine-Catalyzed Aldol Reaction Pathways Catalyzed by the Bifunctional Amino Quaternary Phosphonium Ion.

Members of a new class of bifunctional amino quaternary phosphonium salts have been synthesized and utilized as catalysts in aldol condensation reactions, as demonstrated herein. These secondary amines feature a phosphonium ion connected by a carbon chain, enabling the quaternary phosphonium ion to engage in distinct cooperative noncovalent interactions. These interactions work in tandem to stabilize different transition state complexes, exclusively controlling competing amine-catalyzed aldol pathways via the Mannich mechanism. Comprehensive mechanistic investigations were conducted through theoretical calculations. This study uncovers a proximity-driven catalytic mechanism in which the distance between the N and the P+ of the bifunctional catalyst emerges as a critical factor determining catalytic efficacy. The method has been demonstrated through its application to the total synthesis of several bioactive natural products.

Light-Regulated Growth, Anatomical, Metabolites Biosynthesis and Transcriptional Changes in Angelica sinensis

Angelica sinensis is an alpine medicinal plant that has been widely used as a general blood tonic and gynecological indications over 2000 years, which depend on the bioactive metabolites (e.g., volatile oils, organic acids, and flavonoids). Although the accumulation of these metabolites is significantly affected by the environmental factors (e.g., altitude, temperature, and sunshine) as found in previous studies, the regulatory mechanism of different lights has not been clearly revealed. Here, growth parameters, contents of bioactive metabolites, and expression levels of related genes were examined when A. sinensis was exposed to different white-light (WL) and UV-B radiation treatments. The results showed that the differences in growth parameters (e.g., plant height, root length, and plant biomass) and leaf tissue characteristics (e.g., leaf thickness, stomatal density and shape, and chloroplast density) were observed under different light treatments. The contents of Z-ligustilide and ferulic acid elevated with the increase of WL (50 to 150 µmol·m2/s) and maximized under the combination of WL-100 and UV-B (107 µW/m2, UV-107) radiation, while the total flavonoids and polysaccharides contents, as well as in vitro antioxidant capacity, elevated with the increasing of WL and UV-B. mRNA transcripts encoding for the biosynthesis of volatile oils, ferulic acid, flavonoids, and polysaccharides were found to be differentially regulated under the different WL and UV-B treatments. These morphological, anatomical, and transcriptional changes are consistent with the elevated bioactive metabolites in A. sinensis under the combination of WL and UV-B. These findings will provide useful references for improving bioactive metabolite production via the cultivation and bioengineering of A. sinensis.

Direct effects of Xenorhabdus spp. cell-free supernatant on Meloidogyne incognita in tomato plants and its impact on entomopathogenic nematodes

Entomopathogenic Xenorhabdus spp. bacteria, symbiont of the nematode Steinernema spp., shows potential for mitigating agricultural pests and diseases through bioactive compound production. The plant-parasitic nematode (PPN) Meloidogyne incognita affects the yield and quality of numerous crops, causing significant economic losses. We speculate that Cell-Free Supernatants (CFS) from Xenorhabdus spp. could reduce the impact of the root-knot nematode (RKN) M. incognita without negatively affecting entomopathogenic nematodes (EPNs), which are considered beneficial organisms. This study explored the activity of seven CFS against M. incognita (two populations, AL05 and Chipiona) and their possible effects on EPNs. The in vitro impact of CFS at 10 %, 40 %, and 90 % concentrations on nematode motility at four and 24 h were tested on the PPN M. incognita and two EPNs, S. feltiae and H. bacteriophora. Additionally, EPN viability and virulence were evaluated at two and five days. On the other hand, tomato plant-mesocosm experiments examined the activity of four CFS on M. incognita reproductive capacity and EPN virulence. In vitro exposure of M. incognita to 90 % concentration of CFS resulted in reductions of activity over 60 % after four hours of expossure in four out of seven CFS. In the in vitro evaluation of two species of EPNs, none of the CFS affected the activity across any tested doses after four hours of exposure nor after 24 h. Plant-mesocosm experiments showed that CFS application significantly reduced RKN galls, egg masses, and galling index. However, the virulence of both EPN species decreased 15 days after application, with a significant impact on S. feltiae. Overall, these findings suggest that CFS could be used as a bio-tool against M. incognita in tomato crops, mitigating its impact on plant growth. However, this study also highlights the necessity of investigating the effects of CFS on non-target organisms.

Effect of the exposure period and concentration of aqueous and alcoholic zingiber (Zingiber officinale) extract on the mean of mortality for hydatid cyst's protocolises.

To determine the anti-protocolises effect of aqueous and alcoholic zingiber extract. The present experimental study was conducted from 01, July 2021 to 15. December, 2021 at the College of Education for Pure Sciences, Iraq, and comprised 25mg/mL, 50mg/mL, 100mg/mL and 200mg/mL concentrations of both aqueous and alcoholic extracts of zingiber officinale that were prepared and used in vitro on hydatid cyst protocolises with 10min, 20min, 30min, 40min, 50min and 60min exposure times. The data was analysed using statistical package for the social sciences (SPSS) version 10 by using ANOVA and t- test to determine the differences between groups. The concentration of 200mg/ml was more efficient against the protocolises for aqueous extract, while the alcoholic extract was effective at both 100mg/ml and 200mg/ml concentrations. There was a positive relationship of the degree of killing with both exposure time and concentration. Zingiber officinale could be a potential bioactive natural product and its active constituents could be isolated and used as anti-protoscolex without any side effects.

Looking for Actives in the Haystack: Merging HRMS2-Based Molecular Networking, Chemometrics, and 13C NMR-Based Dereplication Approaches.

The identification of bioactive natural products (NPs) in complex mixtures has become an important subject of contemporary NP research. In an attempt to address this challenge, the present work proposes an integrated strategy that combines tandem mass spectrometry (MS2)-based molecular networking (MN), a partial least-squares (PLS) chemometric model, as well as 13C NMR-based dereplication using MixONat software. In addition, an advanced glycation end product (AGEs) assay was used for activity evaluation. The approach was implemented on a Garcinia parvifolia bark extract that comprised a high content of prenylated xanthones and had previously shown a notable inhibitory effect on AGE formation. As a main result, the proposed strategy permitted the identification of potentially active metabolites within complex mixtures and their annotation with a higher level of confidence by NMR data. Overall, this comprehensive approach provides a powerful and efficient solution for the targeting and annotating of active compounds in complex NP mixtures.

MEDICAGO sativa-mediated green synthesis of Zinc nano-complex: Impacts on the phytochemical properties of Hyssopus officinalis under Alkaline stress

The purpose of this study was to investigate the interaction between sodium bicarbonate stress (SBCS) (0, 10, 20, and 40 mM) and zinc nanocomplex (Zn NC) (0, 1, 2, and 4 mM) on the growth and bioactive compounds of Hyssopus officinalis L. plants at the growth stage. The application of Zn NC increased essential oil (EO) production and the biosynthesis of phenolic compounds (PCs) and flavonoids in the plant. The accumulation of these compounds amplified the plant's antioxidant capacity compared to control. Treatment with Zn NC increased these compounds significantly more than alkalinity. 2 mM and 4 mM Zn NCs increased average APX activity substantially by 37 % and 55 %, respectively. The oxidative damage and depletion of mineral nutrients in the leaves were caused by SBCS. However, Zn NC-treated plants significantly increased nitrogen, phosphorus, potassium, zinc, and iron concentrations in the bicarbonate-stressed plants. A 44 % increase in proline content with 20 mM SBCS and 4 mM Zn NCs compared to control was revealed. In alkaline soils, Zn NC can be a beneficial and environmentally acceptable zinc supply that increases plant growth and bioactive compound production. Totally, applying 2 and 4 mM Zn NC treatment can counteract the negative effects of SBCS on plant growth and nutrient uptake.

Chemical composition and antimicrobial activity of Plinia rivularis essential oil against multidrug-resistant bacteria

IntroductionThe increasingly common occurrences of multidrug-resistant bacteria represent a global health threat and the discovery of new alternative remedies is necessary. The use of essential oils (EOs) in the treatment of many pathogenic bacteria is promising and several examples have already been highlighted regarding their inhibitory action. Among the botanical families, Myrtaceae stands out for presenting important species that supply bioactive products. MethodsIn this work we investigate the chemical composition of Plinia rivularis (Myrtaceae) leaf EO and its antibacterial activity against resistant and non-resistant bacteria. The EO was obtained by two methods, hydrodistillation and steam distillation. Gas chromatography-flame ionization detector (GC-FID), gas chromatograph-mass spectrometry (GC-MS), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR) were the techniques used in the EO chemical characterization. ResultsThe EOs were obtained with yields of 0.37 and 0.16% by hydrodistillation and steam distillation methods, respectively. The analyzes revealed the EOs chemical profile showing the compounds 2H-benzocyclohepten-2-one,3,4,4a,5,6,7,8,9-octahydro-4a-methyl (synonym: 4a-methyl-3,4,4a,5,6,7,8,9-octahydro-2H-benzo[7]annulen-2-one), rosifoliol, β-eudesmol and the diterpene kaurene as main constituents. Through preparative thin-layer chromatography (PTLC), it was possible to obtain the diterpene kaurene with a content of 91%, which was also characterized by NMR. The minimum inhibitory concentrations of EO against bacteria ranged from 0.56 to 2.25 mg.ml−1 and 2.25–36 mg.ml−1 for sensitive and resistant bacteria, respectively. Also, EO showed synergistic activity with amikacin and cefotaxime against carbapenem-resistant Pseudomonas aeruginosa (KPC). ConclusionsThis is the first report on the chemical composition of P. rivularis EO. Comparison of extraction methods showed variation in yields and small changes in component content. The EO demonstrated activity against resistant and non-resistant bacteria. In addition, the synergistic effect of EO against resistant bacteria may be explored in future studies.

Natural Products from Marine-Derived Fungi with Anti-Inflammatory Activity.

Inflammation is considered as one of the most primary protective innate immunity responses, closely related to the body's defense mechanism for responding to chemical, biological infections, or physical injuries. Furthermore, prolonged inflammation is undesirable, playing an important role in the development of various diseases, such as heart disease, diabetes, Alzheimer's disease, atherosclerosis, rheumatoid arthritis, and even certain cancers. Marine-derived fungi represent promising sources of structurally novel bioactive natural products, and have been a focus of research for the development of anti-inflammatory drugs. This review covers secondary metabolites with anti-inflammatory activities from marine-derived fungi, over the period spanning August 2018 to July 2024. A total of 285 anti-inflammatory metabolites, including 156 novel compounds and 11 with novel skeleton structures, are described. Their structures are categorized into five categories: terpenoids, polyketides, nitrogen-containing compounds, steroids, and other classes. The biological targets, as well as the in vitro and in vivo screening models, were surveyed and statistically summarized. This paper aims to offer valuable insights to researchers in the exploration of natural products and the discovery of anti-inflammatory drugs.

Molecular Characteristics and Expression Patterns of Carotenoid Cleavage Oxygenase Family Genes in Rice (Oryza sativa L.)

Carotenoid cleavage oxygenases (CCOs) cleave carotenoid molecules to produce bioactive products that influence the synthesis of hormones such as abscisic acid (ABA) and strigolactones (SL), which regulate plant growth, development, and stress adaptation. Here, to explore the molecular characteristics of all members of the OsCCO family in rice, fourteen OsCCO family genes were identified in the genome-wide study. The results revealed that the OsCCO family included one OsNCED and four OsCCD subfamilies. The OsCCO family was phylogenetically close to members of the maize ZmCCO family and the Sorghum SbCCO family. A collinearity relationship was observed between OsNCED3 and OsNCED5 in rice, as well as OsCCD7 and OsNCED5 between rice and Arabidopsis, Sorghum, and maize. OsCCD4a and OsCCD7 were the key members in the protein interaction network of the OsCCO family, which was involved in the catabolic processes of carotenoids and terpenoid compounds. miRNAs targeting OsCCO family members were mostly involved in the abiotic stress response, and RNA-seq data further confirmed the molecular properties of OsCCO family genes in response to abiotic stress and hormone induction. qRT-PCR analysis showed the differential expression patterns of OsCCO members across various rice organs. Notably, OsCCD1 showed relatively high expression levels in all organs except for ripening seeds and endosperm. OsNCED2a, OsNCED3, OsCCD1, OsCCD4a, OsCCD7, OsCCD8a, and OsCCD8e were potentially involved in plant growth and differentiation. Meanwhile, OsNCED2a, OsNCED2b, OsNCED5, OsCCD8b, and OsCCD8d were associated with reproductive organ development, flowering, and seed formation. OsNCED3, OsCCD4b, OsCCD4c, OsCCD8b, and OsCCD8c were related to assimilate transport and seed maturation. These findings provide a theoretical basis for further functional analysis of the OsCCO family.

Modular Cloning Tools for Streptomyces spp. and Application to the De Novo Biosynthesis of Flavokermesic Acid.

The filamentous Streptomyces are among the most prolific producers of bioactive natural products and are thus attractive chassis for the heterologous expression of native and designed biosynthetic pathways. Although suitable Streptomyces hosts exist, including genetically engineered cluster-free mutants, the approach is currently limited by the relative paucity of synthetic biology tools facilitating the de novo assembly of multicomponent gene clusters. Here, we report a modular system (MoClo) for Streptomyces including a set of adapted vectors and genetic elements, which allow for the construction of complete genetic circuits. Critical functional validation of each of the elements was obtained using the previously reported β-glucuronidase (GusA) reporter system. Furthermore, we provide proof-of-principle for the toolbox inS. albus, demonstrating the efficient assembly of a biosynthetic pathway to flavokermesic acid (FK), an advanced precursor of the commercially valuable carminic acid.

Unveiling Microbial Dynamics and Gene Expression in Legume–Buffel Grass Coculture Systems for Sustainable Agriculture

Legumes enhance pasture health and soil productivity by fixing atmospheric nitrogen and boosting soil microbiota. We investigated the effects of tropical pasture legumes, including butterfly pea (Clitoria ternatea), seca stylo (Stylosanthes scabra), desmanthus (Desmanthus virgatus), lablab (Lablab purpureus), and Wynn cassia (Chamaecrista rotundifolia), on the soil microbial community and buffel grass (Cenchrus ciliaris) gene expression. Additionally, we explored the impact of a phytogenic bioactive product (PHY) in the coculture system. A pot trial using soil enriched with cow paunch compost included four treatments: monoculture of buffel grass and five legume species with and without PHY supplementation and coculture of buffel grass with each legume species with and without PHY supplementation. Actinobacteriota and Firmicutes were the dominant bacterial phyla. Regardless of PHY application, the coculture of buffel grass with legumes positively influenced microbial composition and diversity. Transcriptomic analysis revealed significant gene expression changes in buffel grass shoots and roots, with each legume uniquely affecting nitrogen metabolism. Lablab and Wynn cassia exhibited similarities in modulating metabolic processes, butterfly pea contributed to mycotoxin detoxification, and desmanthus balanced cell death and growth. Seca stylo enhanced root cell growth and regeneration. These findings offer insights for optimizing legume–grass coculture systems, enhancing soil activity and promoting sustainable agriculture.

Ultrasound-assisted Synthesis of Novel 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3, 4-thiadiazol-5-yl]-3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazoles: Anticancer Activities, Apoptotic, Cell Cycle, Molecular Docking, and ADMET Studies

Abstract: A novel series of 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3,4-thiadiazol-5-yl]-3-(2-oxo-2Hchromen- 3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazoles (2a-i) and 3 was synthesized in good yields. The methodology was depended on a one-pot four-components reaction of hydrazine hydrate, alkyl(aryl) isothiocyanate, 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (1), and acetic anhydride in acetic acid under ultrasound irradiation. The spectral tools confirmed the structures of all synthesized compounds. Using the standard SRB method, the designed compounds were screened for their in vitro cytotoxicity properties against PC3, HepG2, and HCT116 human cancer cell lines. Products 2a and 2c worked best against all cancer cells tested, as well as doxorubicin. Apoptosis and cell cycle analyses were performed for the bioactive products 2a and 2c. Both products strongly impacted all tumor cells in the late apoptotic pathway and significantly inhibited all cancer cell types under investigation in both the S and G2 phases. After that, a molecular docking study was carried out on products 2a and 2c to investigate how they interact with the CDK-8 receptor. The ADMET prediction suggested that these bioactive products may be effective anticancer treatments.

Diversity of Host Species and Optimized Cultivation Practices for Enhanced Bioactive Compound Production in Cordyceps militaris

Cordyceps militaris, recognized for its diverse and potent medicinal properties, plays a critical role in herbal medicine. This study investigates the genus Cordyceps, particularly focusing on C. militaris, a species widely utilized in East Asian traditional medicine for its therapeutic properties. C. militaris is rich in bioactive compounds, including cordycepin, adenosine, polysaccharides, ergosterol, and mannitol, which contribute to its broad physiological activities. The research aims to explore the diversity of host species in the cultivation of C. militaris and assess their impact on the biological activity and chemical composition of the fungus. The study highlights the variability in the efficacy of bioactive compounds due to different cultivation conditions and host species, emphasizing the need for standardized cultivation practices. Advances in genetic engineering and fermentation technology have significantly enhanced the production of these metabolites, supporting the sustainable scale-up of C. militaris cultivation. Future research should continue to explore the molecular mechanisms of its bioactive compounds, identify new clinical applications, and improve production efficiency and environmental sustainability. This comprehensive review provides insights for researchers, healthcare professionals, and cultivators on optimizing C. militaris for medicinal and commercial applications.