Noteworthy Biological Activities Research Articles

1,2-Dihydroxy-9H-Xanthen-9-One, a Multifunctional Nature-Inspired Active Ingredient

Incorporating antioxidants into cosmetics is the mainstay for developing new products to mitigate skin aging. However, identifying novel multifunctional antioxidant ingredients with additional relevant properties that block the skin hallmarks of aging is a very striking strategy. Many natural compounds, including xanthones, have demonstrated biologically notable properties. In particular, 1,2-dihydroxy-9H-xanthen-9-one (1,2-DHX) has inhibitory activity against skin enzymes, and metal-chelating and radical-scavenging activities. Therefore, 1,2-DHX is an attractive molecule for cosmetic purposes. With this goal in mind, the anti-inflammatory, antioxidant, and anti-allergic potentials of 1,2-DHX were investigated. 1,2-DHX demonstrated anti-inflammatory properties by inhibiting the synthesis of specific pro-inflammatory mediators, including interleukin-6 (IL-6) and prostaglandin E2 (PGE2), in human macrophages. This xanthone did not elicit sensitization reactions and did inhibit allergic reactions triggered by a strong skin allergen, suggesting its potential as an anti-allergic compound. 1,2-DHX also revealed mitochondrial antioxidant activity by mitigating rotenone-induced oxidative stress in macrophages by up to 40%. Overall, 1,2-DHX displayed a safety profile and noteworthy biological activities, highlighting its multifunctional profile as an active cosmetic ingredient with anti-inflammatory, antioxidant, and anti-allergic properties.

The Impact of Carrageenan on Pharmascience

Abstract: Carrageenan (CG) a sulfated polysaccharide (SP) is produced using a variety of seaweeds from the Rhodophyceae family. This type of seaweed is available in areas, like the Atlantic Ocean close to Great Britain, Europe, and North America. Carrageenan has been permitted for the use as food items with the European additive E-number E407. Carrageenan is a widely used polysaccharide derived from red seaweed and is known for its various applications in the chemical, biological, and pharmaceutical fields. It delves into its versatile applications across various sub areas, spanning from the food to the pharmaceutical industry. A significant emphasis is placed on the intricate roles of carrageenan in pharmaceutical science, where it serves as both a drug carrier agent and an active ingredient, owing to its noteworthy biological activity. This review aims to provide a comprehensive overview of carrageenan's versatile applications, with a focus on its chemical properties, biological activities, and pharmaceutical uses. The pharmaceutical applications of carrageenan are further categorized into various subparts, including its role in treating diseases and its use in drug delivery systems, such as topical, oral, nasal, and unconventional routes. The review also incorporates the most recent developments in clinical trials involving carrageenan and its updated applications, drawing from authoritative sources. This comprehensive analysis aims to offer readers a clear understanding of carrageenan's multifaceted nature and its evolving significance in diverse industries.

Botanical, phytochemical and pharmacological profile of the mangrove plant Kandelia candel (L.) Druce

Kandelia candel L. Druce (family Rhizophoraceae) is a true / major mangrove that has a wide-spread distribution along the coastal areas of the Indo-west Pacific region of the earth. It is commonly found along the coasts of India and a few South East Asian countries. Its parts have numerous applications in leather, textile, furniture industries, and is also used by the traditional health practitioners / healers to treat diabetes. It is known to be producing a variety of phytochemicals. Extracts and compounds isolated from K. candel have exhibited noteworthy biological activities. An attempt has been made to compile the up-to-date information on this mangrove plant from globally recognised scientific databases. This review would provide necessary informationtoformulate the possible application of this common mangrove in standard as well as complementary medicine.

Phytochemical and Pharmacological Profile of Plants from Genus Buxus: A Review

Buxus is an evergreen shrub of the Buxaceae family. A comprehensive survey of the literature has been conducted, revealing that alkaloids are the predominant metabolites characterized by their noteworthy biological activities. Of particular interest are the alkaloids that have exhibited significant cytotoxic activity against various cell lines, including HL-60, SMMC-7721, A549, MCF- 7, SW480, ES2, and A2780 cell lines. CVB-D, buxbodine B, and buxmicrophyllines F can inhibit the growth of tumor cells and induce tumor cell apoptosis. This article reviews the chemical constituents, antitumor effect, and mechanism of Buxus alkaloids in recent years so as to provide a reference for its further development and utilization of medicinal plants of the genus Buxus.

Baicalin relieves complement alternative pathway activation-induced lung inflammation through inhibition of NF-κB pathway

IntroductionAcute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation.MethodsActivation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue.ResultsBaicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue.ConclusionBaicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

Spectroscopic, anti-cancer, anti-bacterial and theoretical studies of new bivalent Schiff base complexes derived from 4-bromo-2,6-dichloroaniline

In this paper, four new mono-nuclear Ni(II), Pd(II), Pt(II) and Zn(II) complexes were prepared by using a bi-dentate Schiff base ligand, (E)-2-(((4-bromo-2,6-dichlorophenyl)imino)methyl)-5-chlorophenol (BrcOH), with bivalent ions in a methanol and distil water mixture as solvent in presence of NaOH as base. The structures of the prepared compounds were characterized by spectroscopic techniques (IR and 1H NMR), CHN analysis, and molar conductivity. The M(II) (Ni, Pd and Pt) ions are four-coordinated by a bi-dentate N2O2 donor ligand, forming square planar geometry, whereas the Zn(II) is coordinated as a tetrahedral geometry. The newly synthesized compounds, which include the Schiff base ligand and its complexes, underwent antibacterial screening against E. coli and S. aureus. The results demonstrated a remarkable and noteworthy biological activity of these compounds against these pathogenic bacterial strains. Different binding energies showed good correlation, with Pd showing the strongest binding. Small energy differences indicated high reactivity, with Ni and Pd complexes being the most reactive. Electrophilicity index exhibited electron-accepting properties, with Zn showing the highest reactivity. The dipole moments showed polarity and charge separation, with Pt having the highest polarity. We evaluated the pharmacokinetic properties (ADME) of a ligand and its metal complexes using the Swiss ADME website. The results of the in-silico prediction of physicochemical properties revealed that ten compounds in total adhered to Lipinski's rule.

Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial-mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development. Despite advancements in CDK5-targeted inhibitor research, the range of compounds available for clinical and preclinical trials remains limited. The marine environment has emerged as a prolific source of diverse natural products with noteworthy biological activities, including anti-cancer properties. In this study, we screened a library of 47,450 marine natural compounds from the comprehensive marine natural product database (CMNPD) to assess their binding affinity with CDK5. Marine compounds demonstrating superior binding affinity compared to a reference compound were identified through high-throughput virtual screening, standard precision and extra-precision Glide docking modes. Refinement of the selected molecules involved evaluating molecular mechanics-generalized born surface area (MM/GBSA) free binding energy. The three most promising compounds, (excoecariphenol B, excoecariphenol A, and zyzzyanone B), along with the reference, exhibiting favorable binding characteristics were chosen for molecular dynamics (MD) simulations for 200 nanoseconds. These compounds demonstrated interaction stability with the target during MD simulations. The marine compounds identified in this study hold potential as effective CDK5 inhibitors and warrant subsequent experimental validation.

Antibacterial and anti-inflammatory activity of plant species used in traditional poultry ethnomedicine in Zimbabwe: A first step to developing alternatives to antibiotic poultry feed additives

Ethnopharmacological relevanceGlobal interest in phytogenic feed additives as alternatives to antibiotics in feed has been spurred by the banning of antibiotic growth promoters by several countries. Suitable plant extracts for development of phytogenic feed additives should have therapeutic value and should also be safe. Aim of studyThe aim of this study was to evaluate the antibacterial, antioxidant and anti-lipoxygenase activities as well as cytotoxicity of selected plant species used in poultry ethnomedicine in Zimbabwe. MethodsAntibacterial activity was determined against three ATCC strains (Staphylococcus aureus, Escherichia coli, Salmonella Enteritidis) and two clinical strains isolated from chickens (Escherichia coli and Salmonella Gallinarum) using a two-fold serial microdilution assay. Qualitative antibacterial bioautography was also carried out using the ATCC strains. Antioxidant activities of crude acetone and methanol extracts were determined using free radical scavenging assays whilst anti-lipoxygenase activity was evaluated using a ferrous oxidation-xylenol orange (FOX) assay. Cytotoxicity was evaluated using a tetrazolium-based colorimetric assay (MTT assay) on Vero monkey kidney cells. ResultsErythrina abyssinica had the best antibacterial activity against both ATCC strains and clinical strains with minimum inhibitory concentration (MIC) values ranging from 0.02 to 0.156 mg/ml. Aloe greatheadii, Adenia gummifera (leaves), Senna singueana and Aloe chabaudii had moderate activity against the poultry pathogens. Bioautography showed that all ten plant species have antibacterial activity against the tested microorganisms with E. abyssinica and S. singueana having prominent bands of inhibition against both Gram-negative and Gram-positive bacteria. The acetone extract of S. singueana and the methanol extract of Euphorbia matabelensis had the most powerful antioxidant activities with mean IC50 values of 1.43 μg/ml and 1.31 μg/ml respectively in the ABTS assay which were comparable with those of the positive controls (ascorbic acid and trolox). Bobgunnia madagascariensis, A. chabaudii, E. abyssinica and Tridactyle bicaudata extracts had reasonable antioxidant activity. The S. singueana extract had the most potent anti-lipoxygenase activity with a mean IC50 value of 1.72 μg/ml. The cytotoxicity results showed that only the acetone extracts of A. greatheadii and S. singueana were relatively safe at concentrations that were active against the tested microorganisms (selective index >1). Regarding anti-lipoxygenase activity, extracts of B. madagascariensis, S. singueana, T. bicaudata and E. matabelensis were more active than toxic (selective index >5) indicating anti-inflammatory potential. ConclusionsThis study showed that S. singueana had a cocktail of therapeutic activity and supports further investigation of this plant species for development of phytogenic poultry feed additives. Other plant species with noteworthy biological activities include B. madagascariensis, E. abyssinica, A. greatheadii, T. bicaudata and E. matabelensis.

In Vitro Anti-Aging Potential Evaluation of Maclura pomifera (Rafin.) Schneider 80% Methanol Extract with Quantitative HPTLC Analysis.

Maclura pomifera (Rafin.) Schneider is a widespread species all around the world, which is also frequently cultured for ornamental purposes. Previous studies revealed that M. pomifera fruits are rich in prenylated isoflavonoids, exhibit noteworthy biological activities, and have probable benefits, particularly, when applied topically. Considering that phenolic compounds are important sources in the development of anti-aging cosmetic products, this study investigated the anti-aging potential of M. pomifera 80% methanolic extract (MPM) by evaluating antioxidant and extracellular matrix degrading enzymes inhibiting activity. For this study, the inhibitory potential of 80% MPM against different enzymes associated with the aging process was evaluated. Given the unequivocal role of oxidative stress in aging, in vitro antioxidant tests were employed as well. Moreover, osajin was determined as the major bioactive isoflavonoid of the sample by high performance thin layer chromatography analysis. Results of the mechanistically different antioxidant assays exhibited notable antioxidant potential of the extract. Inhibition potential of MPM against hyaluronidase, collagenase, and elastase enzymes, which are directly linked to acceleration of the aging process, was investigated and results revealed that MPM inhibited the aforementioned enzymes explicitly. MPM had notable phenolic and flavonoid content; 113.92 ± 2.26 mg gallic acid equivalent/g and 66.41 ± 0.74 mg QE/g, respectively. When total antioxidant capacity assays were considered, it is possible to suggest that MPM is a promising anti-aging agent. As a result, this study discloses that extracts of fruits of M. pomifera have significant anti-aging potential and may be used for this purpose.

Synthesis and Nano-Sized Characterization of Bioactive Oregano Essential Oil Molecule-Loaded Small Unilamellar Nanoliposomes with Antifungal Potentialities.

The development of greener nano-constructs with noteworthy biological activity is of supreme interest, as a robust choice to minimize the extensive use of synthetic drugs. Essential oils (EOs) and their constituents offer medicinal potentialities because of their extensive biological activity, including the inhibition of fungi species. However, their application as natural antifungal agents are limited due to their volatility, low stability, and restricted administration routes. Nanotechnology is receiving particular attention to overcome the drawbacks of EOs such as volatility, degradation, and high sensitivity to environmental/external factors. For the aforementioned reasons, nanoencapsulation of bioactive compounds, for instance, EOs, facilitates protection and controlled-release attributes. Nanoliposomes are bilayer vesicles, at nanoscale, composed of phospholipids, and can encapsulate hydrophilic and hydrophobic compounds. Considering the above critiques, herein, we report the in-house fabrication and nano-size characterization of bioactive oregano essential oil (Origanum vulgare L.) (OEO) molecules loaded with small unilamellar vesicles (SUV) nanoliposomes. The study was focused on three main points: (1) multi-compositional fabrication nanoliposomes using a thin film hydration–sonication method; (2) nano-size characterization using various analytical and imaging techniques; and (3) antifungal efficacy of as-developed OEO nanoliposomes against Trichophyton rubrum (T. rubrum) by performing the mycelial growth inhibition test (MGI). The mean size of the nanoliposomes was around 77.46 ± 0.66 nm and 110.4 ± 0.98 nm, polydispersity index (PdI) of 0.413 ± 0.015, zeta potential values up to −36.94 ± 0.36 mV were obtained by dynamic light scattering (DLS). and spherical morphology was confirmed by scanning electron microscopy (SEM). The presence of OEO into nanoliposomes was displayed by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. Entrapment efficiency values of 79.55 ± 6.9% were achieved for OEO nanoliposomes. In vitro antifungal activity of nanoliposomes tested against T. rubrum strains revealed that OEO nanoliposomes exhibited the highest MGI, 81.66 ± 0.86%, at a concentration of 1.5 µL/mL compared to the rest of the formulations. In summary, this work showed that bioactive OEO molecules with loaded nanoliposomes could be used as natural antifungal agents for therapeutical purposes against T. rubrum.

Isolation of bioactive compounds from Rumex hastatus extract and their biological evaluation and docking study as potential anti-oxidant and anti-urease agents.

Herein, the methanolic extract of Rumex hastatus was prepared and subjected to silica gel column chromatographic separation for purification. The chromatographic analysis yielded four bioactive compounds namely, 1,8-dihydroxy-3-methyl-anthraquinone (C1, chrysophanol), 3-methoxy-7-methyl-1,5-dihydroxy-anthraquinone (C2), 6-methyl-1,3,7-trihydroxy-anthraquinone (C3), and 4-hydroxycinnamic acid (C4). The structures of all the isolated bio-entities were elucidated by spectroscopic analysis (1D, 2D-NMR, and MS). The biological potentialities of bioactive compounds were evaluated by determining their antioxidant and anti-urease activities. The results revealed that compound 1 showed the highest nitrite radical scavenging activity (IC50 =0.39mM) followed by C2 and C4 (IC50 =0.45) mM and C3 (IC50 =0.47mM). Similarly, the determined IC50 values foranti-urease activity were C2 (IC50 =0.39mM), C1 (IC50 =0.40), C4 (IC50 =0.41), and C3 (IC50 =44). Molecular docking study revealed maximum interactions among the hydroxyl group of all compounds. In conclusion, Rumex hastatus extract could be a promising alternative to chemical additives in pharmaceutical industries due to its noteworthy biological activities. PRACTICAL APPLICATIONS: As we have shown in this study that Rumex hastatus is a prolific source of biologically active compounds with potent antioxidant and anti-urease activities, therefore, R. hastatus extract could be used as a promising alternative to chemical additives in pharmaceutical industries due to its unique compounds and noteworthy biological activities.

Synthesis of anti-4-phenoxyphenylaminoglyoxime and its some transition metal complexes: Spectral, DFT, electrochemical and anticancer activity studies

anti-4-phenoxyphenylaminoglyoxime (LH2) was synthesized starting from 4-aminodiphenylether and anti-chloroglyoxime in absolute ethanol. Then, mononuclear complexes [Ni(II) and Cu(II)] of LH2 were synthesized with the metal:ligand ratio of 1:2. The LH2 and its complexes [Ni(LH)2 and Cu(LH)2] were characterized by elemental analysis, FT-IR, Raman, UV–vis, thermogravimetric analysis (TGA), 1H NMR, 13C NMR, heteronuclear multiple bond correlation (HMBC) spectroscopy and theoretical DFT studies. Also, redox properties of the ligand and its complexes were investigated by cyclic voltammetry in DMSO solution at room temperature. Conformational space was scanned with molecular mechanic simulations and then the possible stable conformers of LH2 ligand were determined by B3LYP/6–311++G (d,p) level calculations. The Ni(LH)2 and Cu(LH)2 metal complexes were modeled theoretically using B3LYP/LanL2DZ level. The theoretical vibrational frequencies were calculated by using optimization calculation levels. The NMR parameters of LH2 ligand, Cu(LH)2 and Ni(LH)2 metal complexes were calculated at mPW1PW91/6-311 + G (2d,p) level. Theoretically calculated values were compared with the related experimental values. The DFT calculation results have been used to predict and interpret the molecular structures of LH2 ligand and its complexes. The geometry around nickel in Ni(LH)2 and around cupper in Cu(LH)2 complex are almost square planar. In addition, we evaluated the efficacy of LH2 ligand and its Ni(LH)2 and Cu(LH)2 complexes in the breast adenocarcinoma cell line (MCF7). Our data showed that the metal compounds affect positively the cytotoxic activity of the ligand (LH2). The metal complexes, especially Ni(LH)2 complex, exhibited noteworthy biological activity against the viability of MCF7 cells.

Immunomodulatory and antineoplastic efficacy of common spices and their connection with phenolic antioxidants

Background: Spices have generally offered a conventional way to avert and heal various communicable and non-communicable diseases due to their efficacy and safety and their noteworthy contribution towards understanding targeted drug action and drug delivery systems. Hence, the current investigation is designed to evaluate the immunomodulatory and antineoplastic efficacy of 15 spices that connect with the flavonoid and total polyphenol ingredients. This study includes the 15 adopted spices and their total flavonoid and polyphenol contents, cell viability assay (MTT), immunomodulatory efficacy (NO, TNF-α), and antineoplastic efficacy (using six cancer cell lines).Methods: The quantification of the flavonoid and phenolic content of methanolic extracts of 15 spices was performed by colorimetric assay. The immunomodulatory efficacy was studied according to their capacity to prevent NO and TNF-α synthesis in LPS stimulated RAW 264.7 macrophages. Cell viability was observed using MTT colorimetric assay. Antineoplastic efficacy was determined with six cancer cell lines, namely liver (HepG2), colon (HT29), breast (MCF7), pancreas (MIA PaCa2), lung (A549) and blood (Raji). Results: The outcome of significant immunomodulatory efficacy of the spices was noted in the following sequences: Acorus calamus L.(Inhibition of NO-49.32 ± 4.29 µg/mL and TNF-α 96.35 ± 8.23 µg/mL)> Alpinia galanga Wild (Inhibition of NO-55.69 ± 5.89µg/mL and TNF-α 102.36 ± 8.96 µg/mL)> Armoracia rusticana Gaerth (Inhibition of NO-82.44 ± 5.98 µg/mL and TNF-α 115.69 ± 7.59)> Capparis spinosa L. (Inhibition of NO-127.59 ± 5.68 µg/mL and TNF-α 123.58 ± 8.56 µg/mL) > Aframomum melegueta K. Schum (Inhibition of NO-169.89 ± 6.89 µg/mL and TNF-α 144.59 ± 7.89 µg/mL). The remaining spices considerably inhibited the generation of NO and TNF-α. All spices studied exhibited highly significant antineoplastic effects against all six cell lines. Noteworthy biological activities were observed in A. calamus, A. galanga, A. rusticana, C. spinose, and A. melegueta which have bulk quantities of polyphenols.Conclusion: Based on the present findings, spices are possible candidates for novel antioxidant, anti-inflammatory, and antineoplastic agents.Keywords: Spices; cancer cell lines; immunomodulatory; antineoplastic; total polyphenol contents

Two Different Selective Ways in the Deprotonation of β‐Bromopropionanilides: β‐Lactams or Acrylanilides Formation.

AbstractThe reactivity of 3‐bromo‐N‐(p‐bromophenyl)propanamide with different bases in an ionic liquid (BMImBF4) and in acetonitrile (ACN) was studied. Two possible deprotonation sites are present in this molecule, leading to different products. When the NH group is deprotonated, a β‐lactam is obtained after internal halide displacement; when the CH2 in alpha to the carbonyl is deprotonated, the corresponding acrylanilide is formed. This study allowed determining the experimental conditions to obtain selectively and in high yields both products starting from the same molecule. In particular, to obtain the acrylanilide Et3N in ACN is to be used, while to obtain selectively the β‐lactam ring the base must be generated by cathodic reduction of a DMF or ACN‐Et4NBF4 solution. These reactions were extended to other β‐bromopropionanilides, allowing to easily synthesize both β‐lactams and acrylanilides, molecules having noteworthy biological activities.

Products of Sulfide/Selenite Interaction Possess Antioxidant Properties, Scavenge Superoxide-Derived Radicals, React with DNA, and Modulate Blood Pressure and Tension of Isolated Thoracic Aorta.

Selenium (Se), an essential trace element, and hydrogen sulfide (H2S), an endogenously produced signalling molecule, affect many physiological and pathological processes. However, the biological effects of their mutual interaction have not yet been investigated. Herein, we have studied the biological and antioxidant effects of the products of the H2S (Na2S)/selenite (Na2SeO3) interaction. As detected by the UV-VIS and EPR spectroscopy, the product(s) of the H2S-Na2SeO3 and H2S-SeCl4 interaction scavenged superoxide-derived radicals and reduced ·cPTIO radical depending on the molar ratio and the preincubation time of the applied interaction mixture. The results confirmed that the transient species are formed rapidly during the interaction and exhibit a noteworthy biological activity. In contrast to H2S or selenite acting on their own, the H2S/selenite mixture cleaved DNA in a bell-shaped manner. Interestingly, selenite protected DNA from the cleavage induced by the products of H2S/H2O2 interaction. The relaxation effect of H2S on isolated thoracic aorta was eliminated when the H2S/selenite mixture was applied. The mixture inhibited the H2S biphasic effect on rat systolic and pulse blood pressure. The results point to the antioxidant properties of products of the H2S/selenite interaction and their effect to react with DNA and influence cardiovascular homeostasis. The effects of the products may contribute to explain some of the biological effects of H2S and/or selenite, and they may imply that a suitable H2S/selenite supplement might have a beneficial effect in pathological conditions arisen, e.g., from oxidative stress.

Prenylated β-diketones, two new additions to the family of biologically active Hypericum perforatum L. (Hypericaceae) secondary metabolites

Two novel β-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures of β-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these β-diketones predominantly exist as two rapidly interconverting β-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St. John's wort. It is therefore not surprising that A displayed a noteworthy biological activity profile as well (including brine shrimp toxicity, antinociceptive, antidepressant and acetylcholinesterase inhibitory activity). β-Diketone A manifested the most outstanding potency as an acetylcholinesterase inhibitor with IC50 value of 1.51 μM pointing again to the β-keto-enol moiety as a promising lead structure for the development of drugs that could lessen symptoms of Alzheimer's disease (such as dementia, depression and pain).

Lycopodium Alkaloids: An Intramolecular Michael Reaction Approach

The Lycopodium alkaloids possess a rich history that has captured the attention of synthetic chemists across the globe. This large family consists of over 250 known natural products with diverse structural features and noteworthy biological activity. Herein, we interweave the synthetic accomplishments by others in the field with our own unified strategy to accessing multiple subfamilies of the Lycopodium alkaloids. This discussion includes lycopodine, the C10-hydroxy Lycopodium alkaloids (10-hydroxylycopodine, deacetylpaniculine and paniculine), pelletierine, cermizine D, fastigiatine, himeradine A, clavolonine and 7-hydroxylycopodine. A unifying feature of much of the work discussed within this account is the use of intramolecular Michael additions to construct key ring systems within the Lycopodium alkaloids. Examples include the use of an intramolecular keto-sulfone Michael reaction and an intramolecular heteroatom Michael reaction.1 General Background on Lycopodium Alkaloids2 Development of a Strategy for Lycopodium Alkaloids2.1 Generalized Strategy2.2 Known Syntheses of C10-Functionalized Lycopodium Alkaloids3 Quinolizidine-Type Alkaloids3.1 Background3.2 Development of the Heteroatom Michael Reaction3.3 Synthesis of the Core Lycopodine Building Block: Pelletierine3.4 Total Synthesis of Cermizine D3.5 Synthesis of the Eastern Half of Himeradine A4 Lycopodine-Type Alkaloids4.1 Total Syntheses of Lycopodine4.1.1 Earlier Racemic Syntheses4.1.2 Approach Toward the Tricyclic Skeleton of Lycopodine: Intramolecular Mannich4.1.3 Enantioselective Total Syntheses of Lycopodine4.2 Total Syntheses of Clavolonine (8-Hydroxylycopodine)4.3 Total Synthesis of 7-Hydroxylycopodine4.4 Synthetic Route for 10-Hydroxy Lycopodium Alkaloids4.4.1 Background4.4.2 Total Syntheses4.4.3 Impact of the C10-Stereochemistry5 Conclusion

Characterization of 2,3-diarylxanthones by electrospray mass spectrometry: gas-phase chemistry versus known antioxidant activity properties.

Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. In the CID-MS/MS spectra of [M+H](+) ions of XH1, XH2 and XH4 the product ions formed due to H2 O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2 O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64Da (concomitant loss of two molecules of H2 O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd.

The MarR-like protein PchR (YvmB) regulates expression of genes involved in pulcherriminic acid biosynthesis and in the initiation of sporulation in Bacillus subtilis.

BackgroundCyclodipeptides and their derivatives constitute a large class of peptide natural products with noteworthy biological activities. In some yeasts and bacterial species, pulcherriminic acid derived from cyclo-L-leucyl-L-leucyl is excreted and chelates free ferric ions to form the pulcherrimin. In Bacillus subtilis, the enzymes YvmC and CypX are known to be involved in pulcherriminic acid biosynthesis. However, the mechanisms controlling the transcription of the yvmC-cypX operon are still unknown.ResultsIn this work, we demonstrated that the B. subtilis YvmB MarR-like regulator is the major transcription factor controlling yvmC-cypX expression. A comprehensive quantitative proteomic analysis revealed a wide and prominent effect of yvmB deletion on proteins involved in cellular processes depending on iron availability. In addition, expression of yvmB depends on iron availability. Further analysis with real-time in vivo transcriptional profiling allowed us to define the YvmB regulon. We identified yvmBA, yvmC-cypX and yvnB for negative regulation and yisI for positive regulation. In combination with genetic approaches, gel mobility shift assays indicated that a 14-bp palindromic motif constitutes the YvmB binding site. It was unexpected that YvmB controls expression of yisI, whose encoding protein plays a negative role in the regulation of the sporulation initiation pathway. YvmB appears as an additional regulatory element into the cell’s decision to grow or sporulate.ConclusionOur findings reveal a possible role of the B. subtilis YvmB regulator in the regulatory networks connected to iron metabolism and to the control of proper timing of sporulation. YvmB was renamed as PchR controlling the pulcherriminic acid biosynthetic pathway of B. subtilis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0807-3) contains supplementary material, which is available to authorized users.