Natural Analogues Research Articles

Organocatalytic Asymmetric [3 + 2] Cyclization: Enantioselective Synthesis of α-Indolyl Pyrrolo[1,2-a]indole Scaffolds.

A novel asymmetric [3 + 2] cyclization of α-indolyl propargylic alcohols with 3-alkyl-1H-indoles via chiral phosphoric acid catalysis has been established. This strategy allowed the synthesis of chiral α-indolyl pyrrolo[1,2-a]indole derivatives with high yields (up to 91%) and excellent enantioselectivities (up to 99% ee), facilitating both the reaction activity and enantioselectivity by using the solvent of CH3CFCl2. Significantly, this protocol will provide an effective synthetic approach for constructing enantioenriched α-indolyl pyrrolo[1,2-a]indole cores of antimalarial natural product isoborreverine analogues.

Trends in High Performance Computing and Quantum Computing

High Performance Computing (HPC) applies different techniques to complex or large-volume applications, relying on both parallel software and hardware, to reduce their execution time compared to running them on a simple computer. On the other hand, Quantum Computing (QC) emerges as a new paradigm that leverages the properties of Quantum Mechanics for computation. QC has an inherently parallel nature and it is expected to solve some problems faster than classical computing. This paper carries out a bibliographic review to examine the point of view of different authors regarding the relationship between HPC and QC. The objective is to determine the trend of this relationship: Will QC replace classical HPC computing?or Will they complement each other? Also, if they were complementary tools, the aim is to answer: How could they be integrated? How will users access these resources?

Resveratrol and Its Natural Analogs Mitigate Immune Dysregulation and Oxidative Imbalance in the Endometriosis Niche Simulated in a Co-Culture System of Endometriotic Cells and Macrophages.

Background: Inflammation and immune cell dysfunction are critical facilitators of endometriosis pathophysiology. Macrophages are renowned for stimulating lesion growth, vascularization, innervation, and pain generation. By combining macrophages and endometriotic cells, we determined if resveratrol and its natural analogs can target the immune dysregulation and oxidative imbalance in endometriosis. Methods: After treatment with compounds (5, 10, 25 µM), we evaluated the expression of key inflammatory and oxidative stress markers, cytokines release, and ROS production by applying q-PCR, ELISA, Cytometric Beads Array, and multiplexed fluorogenic staining and flow cytometry analysis with bioimaging. Results: The results showed that endometriosis-related macrophages treated with stilbenes have impaired expression of pro-inflammatory markers (IL6, IL8, IL1B, TNF, CCL2, CXCL10, PTGS2). The effect of resveratrol, pterostilbene, and piceatannol was observed, especially in reducing IL1B, CCL2, and CXCL10 genes up to 3.5-, 5-, and 7.7-fold at 25 µM, respectively. Also, with piceatannol or polydatin exposure, the IL-6 decrease was noticeable. This study reported an antioxidant effect by reducing ROS-positive cells from 96% to 48% by pterostilbene. Results from flow cytometry correlated with the transcript activation of detoxification enzymes (SOD, GPX). Conclusions: Prospects for potential therapy based on regulating the immune microenvironment and reducing the accumulation of free radicals with stilbenes application were described in the article.

Cyclization by Intramolecular Suzuki-Miyaura Cross-Coupling - A Review.

Ring systems of all sizes are frequent core or substructures in natural products and they are important elements of many drug molecules, as they often confer high binding affinity to and selectivity for disease-relevant biological targets. A uniform key transformation in the synthesis of such structures is the cyclization step. Among the various approaches that have been developed for ring closure, the intramolecular Suzuki-Miyaura reaction has emerged as a powerful option for the construction of normal- and medium-sized rings as well as macrocycles, due to its stereospecificity, the mild reaction conditions, and the non-toxic nature of the boron by-products. In this review, we summarize the state-of-the-art of the application of intramolecular Suzuki-Miyaura cross-coupling reactions in the construction of (macro)cyclic frameworks of natural products and bioactive molecules of synthetic origin, covering (mostly) examples that have been reported since 2015. Target molecules prepared via intramolecular Suzuki-Miyaura cross-coupling as a key step range from natural products / natural product analogs to synthetic drug candidates, featuring ring sizes from 4 to >>12. We highlight the utility, scope, and limitations of the reaction for different ring sizes and arrays of functional groups. Where possible, comparisons with other methods of cyclization are provided.

New opportunities in produced water management: A market-based approach to produced water trading

Produced water (PW) is a byproduct of oil and gas (O&G) production. Obtained alongside the more valuable energy products, PW is usually characterized by high levels of salinity and often contains many contaminants (chemicals, soluble and insoluble oil, organics, etc.) making it unsuitable for release without substantial treatment. Couple this with the fact that PW is typically obtained at multiple times the rate of oil or gas, and the added transport, treatment, and disposal costs become a serious challenge for operators. These realities have led to ad-hoc practices including cooperation between industry competitors to recycle, share, or otherwise mitigate PW costs. The National Energy Technology Laboratory (NETL) in partnership with the Ground Water Protection Council (GWPC) is pursuing novel technology solutions to address PW issues that complement or improve ad-hoc practices adopted by operators. In this paper, we observe that well-established market management practices used in electrical power generation have natural analogues in the PW supply chain. These parallels open up a new line of research where we view PW management as a market equilibrium problem, and explore solutions that foster active and data-based collaboration among operators through market structures similar to power markets, with the ultimate objective of improving PW management costs and recycling rates. We make a case for our observations, present a PW market clearing optimization model that shows how such a market system could operate in the O&G space, and provide an illustrative case study for demonstration.

A Survey on Parallel Nature Inspired Algorithms

A Survey on Parallel Nature Inspired Algorithms

Brownian motion in a vector space over a local field is a scaling limit

For any natural number d, the Vladimirov–Taibleson operator is a natural analogue of the Laplace operator for complex-valued functions on a d-dimensional vector space V over a local field K. Just as the Laplace operator on L2(Rd) is the infinitesimal generator of Brownian motion with state space Rd, the Vladimirov–Taibleson operator on L2(V) is the infinitesimal generator of real-time Brownian motion with state space V. This study deepens the formal analogy between the two types of diffusion processes by demonstrating that both are scaling limits of discrete-time random walks on a discrete group. It generalizes the earlier works, which restricted V to be the p-adic numbers.

Należności publicznoprawne jako przedmiot egzekucji sądowej w Polsce i w Austrii

The paper presents results of benchmarking legal solutions adopted in Poland and in Austria with respect to methods of enforcing public-legal receivables. A starting point were the relationships between court and administrative enforcement in the Austrian system, indicating the parallel nature of both ways of claiming financial dues. In the next part of the study, the evolution of Polish regulations was presented in this regard. Initially, like in Austria, they established the equivalency of court and administrative enforcement proceedings, gradually including more and more deviations from this concept, until the complete separation of both proceedings, which took place finally in 2001, as a result of granting the right to carry out enforcement against real properties to administrative enforcement authorities. In the present legal system, public-legal receivables are subject to court enforcement in exceptional cases only, under a special regulation, but even in such instances the court mode of enforcement proceedings is not exclusive. This proves the existence in the Polish legislation of a continuous trend to separate court enforcement proceedings from administrative ones, attributing a predominant role in enforcement of public-legal receivables to the latter. Keywords: administrative enforcement, court enforcement, public-legal receivables, administrative enforcement title, Austrian enforcement law

Homomorphisms of quantum hypergraphs

We introduce quantum homomorphisms between quantum hypergraphs through the existence of perfect strategies for quantum non-local games, canonically associated with the quantum hypergraphs. We show that the relation of homomorphism of a given type satisfies natural analogues of the properties of a pre-order. We show that quantum hypergraph homomorphisms of local type are closely related, and in some cases identical, to the TRO equivalence of finite dimensionally acting operator spaces, canonically associated with the hypergraphs.

S-Methyl-L-cysteine targeting MsrA attenuates Ang II-induced oxidative stress and atrial remodeling via the p38 MAPK signaling pathway.

Atrial fibrillation (AF) is the most prevalent sustained tachyarrhythmia in patients with cardiovascular diseases. Recently, it has been discovered that oxidative stress is an important contributor to AF. Therefore, antioxidant therapies for AF have great potential for clinical applications. Methionine, a sulfur-containing amino acid residue other than cysteine, is recognized as a functional redox switch, which could be rescued from the reversible oxidation of methionine sulfoxide by methionine sulfoxide reductase A (MsrA). S-Methyl-L-cysteine (SMLC), a natural analogue of Met, which is abundantly found in garlic and cabbage, could substitute for Met oxidations and mediate MsrA to scavenge free radicals. However, whether SMLC alleviates AF is unclear. This study aims to clarify the effects of SMLC on AF and elucidate the underlying pharmacological and molecular mechanisms. In vivo, SMLC (70, 140 and 280 mg kg-1 day-1) was orally administered to mice for 4 weeks with angiotensin II (Ang II) by subcutaneous infusion using osmotic pumps to induce AF. Ang II significantly prompted high AF susceptibility and atrial remodeling characterized by oxidative stress, conductive dysfunction and fibrosis. SMLC played a remarkable protective role in Ang II-induced atrial remodeling dose-dependently. Moreover, RNA sequencing was performed on atrial tissues to identify the differentially expressed mRNA, which was to screen out MSRA, CAMK2 and MAPK signaling pathways. Western blots confirmed that Ang II-induced downregulation of MsrA and upregulation of oxidized CaMKII (ox-CaMKII) and p38 MAPK could be reversed in a concentration-dependent manner by SMLC. To investigate the underlying mechanisms, HL-1 cells (mouse atria-derived cardiomyocytes) treated with Ang II were used for an in vitro model. SMLC alleviated Ang II-induced cytotoxicity, mitochondrial damage and oxidative stress. Additionally, knockdown MsrA could attenuate the protective effects of SMLC, which were eliminated by the p38 MAPK inhibitor SB203580. In summary, the present study demonstrates that SMLC protects against atrial remodeling in AF by inhibiting oxidative stress through the mediation of the MsrA/p38 MAPK signaling pathway.

In Silico and In Vitro Evaluation of Bioactive Compounds of Vallisneria spiralis L. against Candida albicans

Background This study focused on the extraction, isolation, characterization, and molecular docking of phytochemicals from Vallisneria spiralis L. to determine its antifungal activity. Natural products and structural analogs have always played an important role in pharmacotherapy, particularly in the treatment of infections and malignancies. Methods Vallisneria spiralis L. leaves were pulverized into a fine powder and extracted using a Soxhlet apparatus, and the crude chloroform extract was separated by flash column chromatography. Thin-layer chromatography was used to assess the obtained fractions. Infrared spectra were obtained using a Perkin Elmer spectrometer. NMR spectra were collected using a Bruker spectrometer. Qualitative phytochemical investigations were performed to identify compounds in the extracts. The susceptibility of the test compound to Candida albicans was assessed using disk diffusion. A docking study was conducted to dock the three-dimensional structures of the extracted phytocompounds of Vallisneria spiralis L. into the receptor site of the target proteins using Autodock software. MD simulations were used to study the dynamic behavior, conformational changes, and stability of the proteins using the top three hit chemicals. Results These results suggest that Vallisneria spiralis L. extract contains various phytoconstituents, including carbohydrates, tannins, flavonoids, steroids, terpenoids, and glycosides. The distinctive functional groups of the extract were identified using a Fourier-Transform Infrared (FTIR) spectrophotometer. Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the structures of the isolated and purified extracts. The antifungal activity of Vallisneria spiralis L. extract against Candida albicans was found to be significantly stronger at a concentration of 200 mg/mL. Conclusion The findings of the study were obtained using in vitro and in silico methods to investigate the antifungal effect of Vallisneria spiralis L., which highlighted it as a potential natural antifungal treatment for Candida infection, which could be further investigated.

Stem Life: A Framework for Understanding the Prebiotic-Biotic Transition

Abiogenesis is frequently envisioned as a linear, ladder-like progression of increasingly complex chemical systems, eventually leading to the ancestors of extant cellular life. This “pre-cladistics” view is in stark contrast to the well-accepted principles of organismal evolutionary biology, as informed by paleontology and phylogenetics. Applying this perspective to origins, I explore the paradigm of “Stem Life,” which embeds abiogenesis within a broader continuity of diversification and extinction of both hereditary lineages and chemical systems. In this new paradigm, extant life’s ancestral lineage emerged alongside and was dependent upon many other complex prebiotic chemical systems, as part of a diverse and fecund prebiosphere. Drawing from several natural history analogies, I show how this shift in perspective enriches our understanding of Origins and directly informs debates on defining Life, the emergence of the Last Universal Common Ancestor (LUCA), and the implications of prebiotic chemical experiments.

Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways.

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.

Spectroscopic insights on defects in self-irradiated natural Zircon: A natural analogue for slag host matrix for Zr-metallic wasteform

Zircon is a proposed slag host matrix associated with the metallic wasteform route developed for Zr-hull management. This study de-alienates the nature of radiation damage in Zr- and Si- sublattice in self-irradiated zircon matrices under long term of geological times using a natural analogue approach. To address this, self-irradiated reddish-brown zircon from Tamil Nadu, India was characterized using spectroscopic techniques such as X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy and Photoluminescence (PL) combined with Monte Carlo Based SRIM calculations. The observations revealed that the “as-received” zircon showed significant radiation damage primarily in the Si-sublattice (Si-O-Si linkages) while retaining its crystallinity, indicating a high degree of radiation resistance. The accumulated alpha-dose and displacements per atom (dpa) were evaluated to be 0.59 × 1018 decays/g and 0.019, respectively using RAMAN and SRIM calculations. Photoluminescence studies reveal that after annealing at 1673 K for 96 h, there was a partial recovery of radiation defects and a decrease in Si-O-Si bonds, although defects from dopant atoms remained unchanged. The damage observed is correlated with the nature of atomic bonding in Si-O and Zr-O bonds. The conclusions drawn suggest that zircon demonstrates considerable durability and selective recovery from radiation damage, making it a promising candidate for radioactive waste management.

High energy density picoliter-scale zinc-air microbatteries for colloidal robotics.

The recent interest in microscopic autonomous systems, including microrobots, colloidal state machines, and smart dust, has created a need for microscale energy storage and harvesting. However, macroscopic materials for energy storage have noted incompatibilities with microfabrication techniques, creating substantial challenges to realizing microscale energy systems. Here, we photolithographically patterned a microscale zinc/platinum/SU-8 system to generate the highest energy density microbattery at the picoliter (10-12 liter) scale. The device scavenges ambient or solution-dissolved oxygen for a zinc oxidation reaction, achieving an energy density ranging from 760 to 1070 watt-hours per liter at scales below 100 micrometers lateral and 2 micrometers thickness in size. The parallel nature of photolithography processes allows 10,000 devices per wafer to be released into solution as colloids with energy stored on board. Within a volume of only 2 picoliters each, these primary microbatteries can deliver open circuit voltages of 1.05 ± 0.12 volts, with total energies ranging from 5.5 ± 0.3 to 7.7 ± 1.0 microjoules and a maximum power near 2.7 nanowatts. We demonstrated that such systems can reliably power a micrometer-sized memristor circuit, providing access to nonvolatile memory. We also cycled power to drive the reversible bending of microscale bimorph actuators at 0.05 hertz for mechanical functions of colloidal robots. Additional capabilities, such as powering two distinct nanosensor types and a clock circuit, were also demonstrated. The high energy density, low volume, and simple configuration promise the mass fabrication and adoption of such picoliter zinc-air batteries for micrometer-scale, colloidal robotics with autonomous functions.

Glycomacromolecules to Tailor Crowded and Heteromultivalent Glycocalyx Mimetics.

The glycocalyx, a complex carbohydrate layer on cell surfaces, plays a crucial role in various biological processes. Understanding native glycocalyces' complexity is challenging due to their intricate and dynamic nature. Simplified mimics of native glycocalyces offer insights into glycocalyx functions but often lack molecular precision and fail to replicate key features of the natural analogues like molecular crowding and heteromultivalency. We introduce membrane-anchoring precision glycomacromolecules synthesized via solid-phase polymer synthesis (SPPoS) and thiol-induced, light-activated controlled radical polymerization (TIRP), enabling the construction of crowded and heteromultivalent glycocalyx mimetics with varying molecular weights and densities in giant unilamellar vesicles (GUVs). The incorporation and dynamics of glycomacromolecules in the GUVs are examined via microscopy and fluorescence correlation spectroscopy (FCS) and studies on lectin-carbohydrate-mediated adhesion of GUVs reveal inhibitory and promotional adhesion effects corresponding to different glycocalyx mimetic compositions, bridging the gap between synthetic models and native analogues.

Laboratory evolution of E. coli with a natural vitamin B12 analog reveals roles for cobamide uptake and adenosylation in methionine synthase-dependent growth.

Bacteria encounter chemically similar nutrients in their environment that impact their growth in distinct ways. Among such nutrients are cobamides, the structurally diverse family of cofactors related to vitamin B12 (cobalamin), which function as cofactors for diverse metabolic processes. Given that different environments contain varying abundances of different cobamides, bacteria are likely to encounter cobamides that enable them to grow robustly as well as those that do not function efficiently for their metabolism. Here, we performed a laboratory evolution of a cobamide-dependent strain of Escherichia coli with pseudocobalamin (pCbl), a cobamide that E. coli uses less effectively than cobalamin for MetH-dependent methionine synthesis, to identify genetic adaptations that lead to improved growth with less-preferred cobamides. After propagating and sequencing nine independent lines and validating the results by constructing targeted mutations, we found that mutations that increase expression of the outer membrane cobamide transporter BtuB are beneficial during growth under cobamide-limiting conditions. Unexpectedly, we also found that overexpression of the cobamide adenosyltransferase BtuR confers a specific growth advantage in pCbl. Characterization of the latter phenotype revealed that BtuR and adenosylated cobamides contribute to optimal MetH-dependent growth. Together, these findings improve our understanding of how bacteria expand their cobamide-dependent metabolic potential.

Editorial: Exploiting the power of biocatalysis: accessing optimized natural products analogues

Editorial: Exploiting the power of biocatalysis: accessing optimized natural products analogues

Strichartz estimates for the Schrödinger equation on negatively curved compact manifolds

We obtain improved Strichartz estimates for solutions of the Schrödinger equation on negatively curved compact manifolds which improve the classical universal results of Burq, Gérard and Tzvetkov [11] in this geometry. In the case where the spatial manifold is a hyperbolic surface we are able to obtain no-loss Lt,xqc-estimates on intervals of length log⁡λ⋅λ−1 for initial data whose frequencies are comparable to λ, which, given the role of the Ehrenfest time, is the natural analog of the universal results in [11]. We also obtain improved endpoint Strichartz estimates for manifolds of nonpositive curvature, which cannot hold for spheres.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.