The hydroxamic acid moiety is part of many bioactive molecules, including several clinical drugs, which can be constructed through, generally, the parent carboxylic acid and a source of hydroxylamine by a variety of methods. Hydroxamic acids compose an remarkable group of N-hydroxy amides with high capacity to chelate certain transition metal ions such as Fe(III), considered siderophores in Nature, and Ni(II), for instance.

During a synthetic program towards the derivatization of natural resinic acids, it was decided to prepare some corresponding hydroxamic acid derivatives with potential biological activity for further studies. There are few reports on hydroxamate-derived terpenoids. It was predicted that adding a hydroxamic acid moiety to the carbon skeleton could enhance the antiproliferative activities or other pharmacological properties, as it occurs in other terpenoid compounds.

In this communication, we describe the several issues that we faced in this generally straightforward conversion. Generally, the carboxylic group needs to be activated towards coupling with hydroxylamine. We screened several methods and realized that the desired conversion is difficult in this kind of substrates. After extensive testing, we propose a new protocol via a phosphate intermediate for better results than standard procedures. A basic computational study on the mechanism of this transformation was also carried out to support our experimental results.

Introduction

Spilanthol (1), or (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide, is a naturally occurring N-alkylamide found in various medicinal plants, notably Heliopsis longipes, widely used in traditional remedies across the globe. Structurally, spilanthol features an unsaturated amide and a conjugated diene system, rendering it an intriguing compound for Diels–Alder cycloaddition reactions. Its use as a renewable scaffold opens a sustainable route for the synthesis of structurally diverse, potentially bioactive heterocycles, contributing to the advancement of green synthetic methodologies.

Methods

Spilanthol (1) was extracted from dried roots of H. longipes via ethanol maceration and purified by column chromatography. Cycloaddition reactions were performed using various dienophiles (1.2 equiv) in suitable solvents (0.2 mM concentration). A range of Brønsted and Lewis acids was evaluated as catalysts. TLC monitored reaction progress, and the crude products were purified by flash chromatography.

Results

A variety of dienophiles, including aldehydes and succinimides, were tested. Among the catalysts screened, only BF₃·OEt₂ effectively promoted the formation of the desired [4+2] cycloadduct. Neither thermal conditions nor other Lewis acids yielded the product, often resulting in decomposition or no reaction. The use of BF₃·OEt₂ yielded a pyran derivative in moderate isolated yield. NMR confirmed the product's structure.

Conclusions

This work highlights spilanthol (1) as a promising, bio-based diene for Diels–Alder chemistry. The use of BF₃·OEt₂ as a promoter enables efficient, one-step access to heterocyclic scaffolds from renewable plant resources. These findings underscore the potential of natural alkamides in green synthetic strategies and their relevance in the development of novel pharmacophores from biomass-derived starting materials.

The world is gradually moving back towards Ayurveda, the root of traditional medical advancement. However, Ayurvedic medicine development faces challenges due to the absence of standardized guidelines for formulation, quality assurance, safety profiling, and efficacy evaluation, unlike allopathic medicine. This gap has resulted in limited data on target-based efficacy or mechanisms of action, especially since most Ayurvedic formulations are polyherbal in nature.

The present study focuses on the standardization of an Ayurvedic formulation, Hingvastika Churna, using HPTLC and performing forced degradation studies on its extract. Piperine and Ferulic acid were selected as marker compounds, and the study was conducted in accordance with ICH guidelines Q1A (R2) and Q2 (R1). An in-house prepared Hingvastika Churna was compared with a marketed formulation to analyze the concentration of these markers. The presence of piperine and ferulic acid was confirmed by comparing the Rf values of the samples with standard markers, which were 0.5 and 0.38, respectively.

After method development and validation, forced degradation studies on both formulations and individual ingredients showed notable losses in concentration under stressed conditions. Acidic conditions resulted in the highest degradation of piperine (38.91%) and ferulic acid (60.96%), followed by oxidative and basic conditions. Piperine showed 35.42% and 35.84% degradation, while ferulic acid showed 39.24% and 39.07% degradation in basic and oxidative conditions, respectively.

This study emphasizes the importance of scientific standardization and stability profiling in Ayurvedic formulations to ensure safety, efficacy, and quality consistency.

Therapeutic peptides are a unique drug class due to their high specificity binding with biological targets. However, low bioavailability of peptides, as well as the lack of enzymatic stability, imposes a number of limitations on their biomedical application. A good strategy to overcome the limitations is the use of peptidomimetics, which are able to imitate the binding and activity of peptides in vitro and in vivo. Peptidomimetics can be obtained by combining natural and synthetic amino acids in a peptide sequence. Various five-membered heterocycles are often use as structural fragments of peptide imitators in order to fix the chain in a certain conformation and increase proteolytic stability. The use of 5-aminomethyl-1,2,4-triazole-3-carboxylic acid derivatives as building blocks of peptidomimetic structures may be a very attractive strategy, in which the tautomeric 1,2,4-triazole fragment is capable to flexible forming of hydrogen bonds on protein surface of the target. At proposed work a number of ethyl 5-aminomethyl-1,2,4-triazole-3-carboxylates and their derivatives as mimetics of aliphatic amino acids were synthesized. Their use as building blocks for synthesizing of peptidomimetics was demonstrated. In addition, by use of a panel of pathogenic and model strains of microorganisms and fungi it was not show any independent activity of the amino acid 1,2,4-triazole mimetics synthesized. This similarity of biological properties of the obtained mimetics and their natural analogues reveals in favor of their bioisosterism. Bioisosterism and geometric similarity of 1,2,4-triazole mimetics and natural amino acid encourages their further use as building blocks of therapeutic peptides.

1. Introduction

Photodynamic therapy (PDT) has emerged as a promising cancer treatment due to its minimal invasiveness and reduced risk of damaging healthy tissues, thus easing the burden on patients. PDT involves the administration of a photosensitizer and the application of specific wavelengths of light to induce targeted photochemical reactions. However, post-treatment residual photosensitizers can cause phototoxicity upon exposure to sunlight, posing a significant challenge. To address this issue, drug delivery systems (DDS) have gained attention for their ability to control drug distribution, enhancing therapeutic efficacy while minimizing side effects.

2. Result and Discussion

In this study, we investigated the use of polymeric micelles as nanocarriers for photosensitizers. These micelles offer tumor-targeted delivery and low systemic toxicity. Photosensitizer-containing block copolymers were synthesized and evaluated for phototoxicity using HT29 cells. The results demonstrated considerable cell toxicity upon light exposure, indicating effective PDT activity. These findings suggest that polymeric micelles represent a promising DDS platform to improve the safety and effectiveness of photodynamic cancer therapy.

3. Experimental part

Polymeric micelles were synthesized via reversible addition–fragmentation chain-transfer (RAFT) polymerization. The cytotoxicity of the obtained compounds was assessed through an MTT assay using HT29 human colon cancer cells.

4. Reference

[1] Y. Uruma; H. Yao; B. Altannavch; N. Hara; C. Lu; P.S. Lai Results in Chemistry 2024 DOI: 10.1016/j.rechem.2024.101499

Stink bugs (Scutelleridae and Pentatomidae) have a big quantity of semiochemical compounds that acting as pheromones, allomones, synomones and kairomones. The main goal of this study is to isolating, identifying and synthesing of the main components of the metathoracic glands of Aelia rostrata, Aelia melanota and Eurygaster integriceps stink bugs.

Extracts of the metathoracic glands of stink bugs males and females (Eurygaster integriceps Aelia rostrata, Aelia melanota) were analyzed by GC-MS. On the base of structural HC-MS results, the main component of metathoracic glands Aelia rostrata, Aelia melanota and Eurygaster integriceps stink bugs was identified, as (E)-2-hexen-1-ol acetate. Additionally, α,β-unsaturated aldehydes with carbon chain lengths ranging from six to eight chain lengths ranging were observed. (E)-2-hexenal, (E)-2-heptenal, (E)-2-octenal, and (E)-2-hexen-1-ol have a strong odor and are strong irritants, providing an easily detectable warning signal and reliable protection.

The synthesis of components with an unsaturated E-fragment was carried out under conditions of phase-transfer catalysis according to the Wittig-Horner reaction. An unsaturated alcohol was converted into the corresponding acetate, in the presence of dimethylaminopyridine (DMAP) as a catalyst [4], using of acetic anhydride. These conditions could reduced the time reaction till 30 minutes and also increased the yield till 90%.

Obtained synthetically lures have been successfully testified for the pheromonitiring of stink bugs (Scutelleridae and Pentatomidae) on the grain crops fields.

Introduction: Rosemary (Salvia rosmarinus) , its most used structural parts are the leaves, fresh or dried. Although it is common, there is little research on its phytochemical composition and antioxidant capacity. This research evaluated the essential oil composition and antioxidant activity of rosemary grown in two areas: urban (Quito) and rural (Atuntaqui, Imbabura).

Experimental Section: Aerial parts of both samples were collected to the extraction using solvent-free microwaves, under controlled conditions of time (40 and 8 minutes) and power (500 and 1350 MW). Identification and quantification of volatile compounds was performed by gas chromatography coupled to mass spectrometry¹ (GC-MS) and DPPH/ABTS assays

Results: The analysis revealed differences in yield, 0.93% in urban and 1.02% in rural areas. In addition, physicochemical parameters were evaluated: solubility and refractive index. Significant statistical differences in content and concentration were found according to the harvest site. Antioxidant activity was determined by DPPH methods obtaining (1.1470 and 1.1729) uM eq Trolox/g for urban and rural rosemary respectively; and ABTS with results in different conditions of 2.3309 and -1.2014 uM eq Trolox/g for urban area and in rural area 3.3840 and -0.9875 uM eq Trolox/g.

Conclusion: geoclimatic conditions influence the composition of rosemary essential oil, highlighting the presence of the contaminant tetrachloroethylene^2, being a component in both oils with concentrations of 2.87% and 13.10% for urban and rural rosemary, respectively. This revelation can be a know-how to use the rosemary species as an ecological fingerprint of the quality of the surrounding ecosystem.

Alzheimer’s disease (AD) figures among the most triggering neurodegenerative disorders, constituting a constant subject of interest for medicinal chemistry researchers. The treatment of such disorders remains a challenge due to the complexity of their pathogenesis. Indeed, many factors are involved in the development of AD including different enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) which inhibition results in anti-AD activity, making the conception of novel AChE/BuChE inhibitors a possible way to manage Alzheimer’s disease. Acridine compounds constitute a known class of heterocycles with many interesting pharmacological activities, the fact that prompted us to investigate the anti-AD activity of a synthesized symmetrical acridine derivative easily synthesized from the condensation of an enaminone derivative and p-fluorobenzaldehyde under microwave irradiation. The docking study was completed using Glide software (Schrodinger suites), and both AChE (pdb: 4EY6) and BuChE (4BDS) were utilized as drug targets. The molecular docking simulation resulted in satisfying docking score values alongside numerous significant interactions indicating the high stability of the investigated compound within the active sites of studied enzymes. Additionally, ADMET prediction was carried out for the assessed acridine derivative in order to explore its drug likeness through its pharmacokinetics and toxicity profiles employing SwissADME, MolSoft, and ProTox-II online servers.

Peptic ulcer disease, affecting almost 20% of the worldwide population, depicts an urgent need for effective treatment due to the limited therapeutic options available and the side effects associated with current drugs. The disease is often linked with Helicobacter pylori infection and NSAID usage, both of which compromise the mucosal lining of the stomach. There is growing evidence that dietary polyphenols can contribute to the prevention and management of various chronic diseases, including cancer and gastrointestinal disorders. Among these, green tea has garnered significant attention due to its rich polyphenolic content and associated health benefits. The abundance of green tea polyphenols (GTPs) exhibits chemoprotective, antimicrobial, and antioxidant properties. This study explores a set of 65 GTPs against penicillin-binding proteins (PBPs) as a molecular target to prevent peptic ulceration. Our molecular docking analysis revealed that the polyphenol ‘Epigallocatechin gallate’ (EGCG) exhibited effective binding affinity towards PBPs (PDB code: 1QMF) with a docking score of -11.23 kcal/mol. Additionally, theaflavin-3-gallate and epigallocatechin also showed strong docking scores. In-silico ADME profiling indicated favorable pharmacokinetics for EGCG, including no AMES toxicity, low hERG inhibition, and good intestinal absorption. Our study highlights EGCG as a potential inhibitor of H. pylori, providing a promising natural therapeutic candidate for the management of peptic ulcer disease.

Computer-aided docking with Alphafold-based protein structure modeling revealed the affinity of the ligand DOLA ((Z)-5-(dimethylamino)-N-(octadec-9-en-1-yl)naphthalene-1-sulfonamide) to key metabolic proteins of insects (Tenebrio molitor, Tribolium castaneum, Locusta migratoria, Lucilia cuprina, Drosophila melanogaster). Affine interactions were found with cytochrome P450 family CYP6 (Ebind -10.4 to -8.9 kcal/mol), which participate in detoxification, hormone and xenobiotic metabolism: CYP6BK19, CYP6a23-like, CYP6FD3, CYP6t1, CYP6g1, CYP6t3, CYP6v1, CYP6a18; and cytochrome P450 family CYP4 (Ebind -10.1 to -8.3 kcal/mol), which participates in fatty acid and foreign compound metabolism: Cyp4aa1, CYP4c3-like, CYP4G102, CYP4G62, CYP4g15, CYP4d, CYP4Q33, CYP4G123.
DOLA also interacted with long-chain fatty acid-CoA ligase (Ebind = -10.0 kcal/mol), fatty acyl-CoA reductases (Ebind -9.7 to -8.2 kcal/mol), CYP18a1 (Ebind = -9.2 kcal/mol), lipocalins (Ebind -8.6 to -8.2 kcal/mol), and fatty acid desaturases (Ebind -8.5 to -8.2 kcal/mol), involved in the metabolism, transport and storage of fatty acids, synthesis of cuticular components, pheromones, and metabolism of ecdysone.
DOLA has been identified as a potential affine ligand for several P450 and fatty acid-converting enzymes. These in silico results will contribute to our understanding of insect biochemistry and will serve as a foundation for further experimental in vitro studies of this compound as a tool for investigating insect metabolism or as a potential population regulator.

Supported by Ministry of Education grant No. 20250893 and State Program for Scientific Research No. 20210560.