Search Results (538)

Polygonum capitatum (PC) is an ethnomedicine with reported antibacterial and anti-inflammatory activities and has been clinically used in urinary tract infection (UTI)-related disorders. However, its in vivo exposure characteristics and metabolically associated therapeutic mechanisms in acute pyelonephritis (AP) remain insufficiently understood. To address this issue, this study aimed to evaluate the therapeutic effects of PC in an Escherichia coli (E. coli)-induced rat model of AP and to explore constituents and metabolic pathways associated with its activity. Different PC extracts were screened for antibacterial and anti-inflammatory activities, and the 70% ethanol extract was selected for further study. Seven major compounds were quantified by HPLC. In AP rats, the pharmacokinetic profiles of these compounds in plasma and the renal cortex were analyzed by microdialysis-coupled HPLC-MS/MS. Pharmacodynamic evaluation included urinary bacterial load, urinalysis, renal function, inflammatory cytokines, and renal histopathology. Exploratory PK–PD analysis, untargeted renal metabolomics, and targeted metabolomics of the tryptophan–kynurenine (Trp–Kyn) pathway were also performed. The 70% ethanol extract of PC exhibited the strongest antibacterial and anti-inflammatory activities. The total content of seven active compounds was 3.85%, with gallic acid being the predominant compound (3.42%). Pharmacokinetic analysis revealed that gallic acid, protocatechuic acid, methyl gallate, and quercitrin achieved relatively high systemic exposure and renal distribution. In AP rats, the pharmacokinetic profiles of several compounds were altered, with increased plasma exposure of protocatechuic acid, vanillic acid, ethyl gallate, and syringic acid, while protocatechuic acid also showed higher exposure in the renal cortex. PC treatment reduced urinary bacterial load, improved renal function and urinalysis parameters, alleviated histopathological injury, and decreased inflammatory mediator levels, particularly in renal tissue. Exploratory PK–PD correlations were observed between several compounds and selected pharmacodynamic indicators. Metabolomic analysis suggested disturbances in glycerophospholipid metabolism and the Trp–Kyn pathway in AP rats, some of which were partially reversed after PC treatment. PC showed antibacterial and anti-inflammatory effects in AP rats. Gallic acid, protocatechuic acid, methyl gallate, and quercitrin may be candidate constituents associated with the therapeutic effects of PC, while modulation of glycerophospholipid metabolism and the Trp–Kyn pathway may be involved in its action against AP. These findings provide preclinical pharmacological evidence supporting the therapeutic potential of PC in AP. Full article

Predicting the solubility of active pharmaceutical ingredients (APIs) in binary aqueous-organic mixtures is critical for formulation design, yet remains challenging. Physics-based models such as COSMO-RS provide a solid theoretical foundation but often struggle with non-ideal mixing behavior in complex systems. This study asks a practical question: when does machine learning actually add value beyond established theory? We compared COSMO-RS with DOOIT2 (Dual-Objective Optimization with Iterative Feature Pruning), a hybrid COSMO-RS/machine-learning correction workflow, across two complementary datasets: 85 structurally diverse APIs and related formulation-relevant compounds (10,140 data points) and 37 acid-centered solutes (6030 data points). The datasets also incorporate newly measured solubilities of lidocaine, benzocaine, and vanillic acid in aqueous 4-formylmorpholine mixtures. DOOIT2 employs rigorous API-out Structured Group K-Fold validation with fold-specific ensemble models to ensure realistic assessment of generalization to unseen compounds. The obtained results are dataset-dependent. For the homogeneous acid series, COSMO-RS already delivers strong predictive performance (RMSD = 0.321, R² = 0.925), and DOOIT2 brings no meaningful improvement (RMSD = 0.310, R² = 0.923). In contrast, for the diverse API set, DOOIT2 reduces RMSD from 0.686 to 0.527 and increases R² from 0.829 to 0.849. Residual analysis indicates that prediction uncertainty is driven primarily by the low-solubility region rather than by a simple monotonic dependence on molecular weight alone. These findings delineate the practical boundaries of machine-learning assistance in solubility prediction and offer clear guidance for formulation scientists. Full article

Background: This study investigated the effects of increasing levels of salinity on leaf phytochemical composition and the antioxidant, antidiabetic, and anti-obesity activities. Method: Three quinoa accessions grown under escalating NaCl treatments had their leaves exposed to various chemical analyses. Polyphenols, tannins, and flavonoids were among the phenolic substances whose concentrations were measured. The phenolic chemicals in the water extract were identified using HPLC-DAD-ESI-MS/MS. In vitro and in silico methods were used to measure anti-radical (DPPH), anti-alpha glucosidase, anti-alpha-amylase, and anti-lipase activities. Results: The results showed that water and ethanol, due to their polarity, were the most effective solvents for extracting phenolic compounds. Additionally, salt application led to a dose-dependent increase in total phenols (TPC), flavonoids (TFC), and tannins (CT) across all accessions. The accession DE-1 exhibited the highest contents with average values of 1453.03–4398.36 mg EGA/100 g DW, 322.7–1090.7 mg CAE/100 g DW, and 77.9–335.96 mg CAE/100 g DW of TPC, TFC, and Tannins, respectively. HPLC-ESI-DAD-MS/MS profiling of phenolic compounds led to identifying 18 constituents, including five major compounds (p-coumaric acid, caffeic acid, vanillic acid, p-coumaroyl hexose, and HHDP-galloyl glucose). Except for p-coumaroyl hexose and HHDP-galloyl glucose, which were extensively biosynthesized/accumulated in the salt-tolerant accession DE-1, the remaining phenolic compounds showed irregular evolution depending on accession and salt concentration. Moreover, ethanol and water extracts were evaluated for their anti-radical and enzyme-inhibitory activities. Conclusion: Salt-stressed DE-1 water extract showed strong antioxidant and enzyme inhibitory activities, indicating potential antidiabetic and anti-obesity effects. These activities were confirmed by in silico analysis. Full article

Phytopathogenic diseases are a major limiting factor in agricultural production. Therefore, scientific research continues to focus on developing effective techniques to mitigate their impact on crop productivity. Seaweed extracts, used as nutritional supplements, organic fertilizers, or bio-pesticides, have demonstrated their ability to enhance plant growth, increase yield, and alleviate the effects of abiotic stress. This study aimed to evaluate the effect of the aqueous extract of Bifurcaria bifurcata, collected from the Atlantic coast of Sidi Bouzid (El Jadida, Morocco), on the growth of Solanum tuberosum L., as well as its bactericidal activity against soft rot caused by Dickeya dadantii. The chemical Characterization revealed that Bifurcaria bifurcata aqueous extract is rich in polar and hydrophilic functional groups. In addition, this extract is particularly rich in phenolic metabolites, particularly phenolic acids, such as p-coumaric acid, ferulic acid, vanillic acid, and caffeic acid, which are known for their potential antimicrobial mechanisms. However, the treatment with 4 g/L extract resulted in a significant reduction in disease symptoms (>60%) and enhanced plant growth parameters, including 21% increase in plant height and 33% increase in leaf number. POX activity increased 6-fold (from 0.12 to 0.7 µmol/min/mg protein), indicating successful elicitation of plant defense mechanisms. The Bifurcaria bifurcata extract could act as novel activators of plant defense mechanisms and serve as potential alternatives to chemical pesticides. Full article

Primary coenzyme Q10 (CoQ10) deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In humans, at least 10 genes (PDSS1, PDSS2 to COQ10) are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status and present as primary CoQ10 deficiency. Furthermore, the genes NDUFA9 and HPDL, whilst not part of the PDSS1, PDSS2 to COQ10 gene sequence, have also been shown to have a crucial role in CoQ10 biosynthesis. A major problem in treating primary CoQ10 deficiencies is the poor bioavailability of supplemental CoQ10, both in terms of lack of absorption from the digestive tract and inability to cross the human blood–brain barrier. Bypass strategies aim to circumvent this problem by using more bioavailable precursor analogues that can enter the cell and be incorporated into the CoQ10 synthesis pathway downstream of the affected enzyme, examples being 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid or vanillic acid, which, in contrast to CoQ10, are small, water-soluble molecules. In this article, we have, therefore, reviewed potential bypass mechanisms for primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10, together with NDUFA9 and HPDL, using such precursors. Most of the published data relating to the bypass therapy of primary CoQ10 deficiency is derived from cell lines or animal models, and few human studies have so far been undertaken. In addition, further research is required to investigate the potential mechanisms by which bypass compounds such as 4-HB may access the human blood–brain barrier (BBB), for example, using in vitro co-culture BBB model systems incorporating CoQ10-deficient neurons. Overall, the objective of this article is, therefore, to systematically review the available data for each of the primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10 together with NDUFA9 and HPDL, in particular to identify the clinical potential of such studies. Full article

Mango (Mangifera indica L.), being a climacteric fruit, is highly perishable due to rapid ripening and post-harvest diseases like anthracnose, which significantly shorten its shelf life and limit long-distance sea export. To mitigate these constraints, a chemical-free secondary metabolite-based formulation (SMsF) was developed to delay ripening and control post-harvest anthracnose during storage. The SMsF possesses dual-action properties and is derived from the culture filtrate of Priestia aryabhattai, exhibiting ACC deaminase activity that restricts ethylene formation. It is also rich in antifungal compounds such as vanillic acid, hydroxybenzoic acid, cryptochlorogenic acid, palmitic acid, and BBIT, which inhibit anthracnose development. Additionally, it contains antioxidants including quercetin, coumaryl quinic acid, oleic acid, and acetylglycitin that enhance shelf life and disease resistance. The efficacy of SMsF was evaluated in mango cv. Banganapalli was stored at 12 ± 1 °C and 85–90% relative humidity under simulated reefer conditions (SRC). Integration of gamma irradiation with SMsF provided superior results in disease control and shelf-life extension. The combined treatment maintained higher fruit firmness (0.86 kg cm⁻²), optimal total soluble solids (14.3 °B), desirable acidity (0.22%), and complete suppression of anthracnose (PDI = 0) up to 40 days of storage under SRC compared with the control. The findings conclusively demonstrate that the synergistic application of SMsF and gamma irradiation effectively regulates ripening, enhances fruit quality, and ensures complete disease suppression, thereby significantly extending storage life. This approach holds strong scientific and commercial significance as a sustainable, residue-free, and export-oriented technology capable of improving long-distance transportation, reducing post-harvest losses, and promoting safe mango trade. Full article

The aim of this in vitro study was to investigate the effects of six phenolic acids applied individually and in combination at concentrations of 0–20 mM on Ambrosia artemisiifolia and soil bacteria. Chlorogenic acid (CGA), p-hydroxybenzoic acid (PHBA), and protocatechuic acid (PKA) were tested on both plants and bacteria, whereas p-coumaric (PCA), vanillic (VA), and ferulic (FA) acids were tested only on soil bacteria. The estimated EC₅₀ for radicle inhibition were 4.9 ± 0.1 mM for PHBA, 4.1 ± 0.7 mM for CGA, 6.6 ± 0.7 mM for PKA, 10.1 ± 0.9 mM for CGA + PHBA + PKA, 4.6 ± 0.4 mM for ferulic, vanillic, and p-coumaric acids (FA + VA + PCA), and 2.5 ± 0.3 mM for the combination of all six phenolic acids. Bacterial strains were less susceptible to individual phenolic acids compared to their combinations. PKA and CGA showed the strongest antibacterial activity, with PKA inhibiting 78% and killing 74% of strains at ≤10 mM, while CGA inhibited 61% and killed 57%. Conversely, PCA and VA had the weakest antibacterial effects, requiring ≥20 mM for complete inhibition. Among test genera, Stenotrophomonas, Bacillus, Peribacillus, and Pseudomonas were more susceptible than Enterobacter and Lelliottia. Subinhibitory concentrations of individual phenolic acids did not affect bacterial motility, except for PKA. The study suggests that VA, PCA and FA alone or combined and PHBA alone, appear promising for weed management. Reduced herbicide strategies may safely incorporate CGA and PKA at concentrations below 2.5 mM. Full article

To investigate the effect of microbial fertilizers on phenolic acids in the cultivation soil of Fritillaria taipaiensis P. Y. Li, a quantitative approach utilizing ultra-high-performance liquid chromatography was applied to assess the phenolic acid levels in both rhizosphere and non-rhizosphere soils of F. taipaiensis P. Y. Li under five different microbial fertilizer regimes. Detection of six key phenolic acids (p-hydroxybenzoic, p-coumaric, vanillic, syringic, chlorogenic, and ferulic) was consistent in all soil samples, regardless of rhizosphere status or inoculation treatment. Among these, chlorogenic acid had the highest content in both rhizosphere (17.651 μg/g, accounting for 55.51%) and non-rhizosphere (25.975 μg/g, accounting for 42.38%) soils, while vanillic acid (0.903 μg/g, accounting for 8.27% in rhizosphere soil) and p-hydroxybenzoic acid (0.086 μg/g, accounting for 1.34% in non-rhizosphere soil) were the lowest in their respective soils. Whereas the control (CK) showed higher levels, inoculation with Claroideoglomus claroideum resulted in a marked decrease in all six phenolic acids within the F. taipaiensis soil. In contrast, the other treatment groups exhibited higher overall phenolic acid content than CK. Correlation analysis indicated a subset of significant positive correlations among phenolic acids in the non-rhizosphere soil; by contrast, their intercorrelations within the rhizosphere soil were universally positive and significant. The phenolic acid content in F. taipaiensis soil was significantly altered by the application of different microbial fertilizers. Among them, C. claroideum was the most effective in reducing phenolic acid accumulation. Full article

Background/Objectives: This study aimed to investigate the phytochemical composition, antioxidant capacity, and anticancer potential of methanol and ethanol extracts of Lactarius deliciosus (L.) Gray in MCF-7 breast cancer cells, focusing on their effects on energy metabolism and related molecular mechanisms. Methods: In L. deliciosus samples, total antioxidant activity and total phenolic content were determined spectrophotometrically, while individual phenolics were classified by HPLC and volatile aromatic compounds (VOCs) were determined by GC-MS. The anticancer effects of L. deliciosus in MCF-7 breast cancer were determined using RT-qPCR with 46 different genes. Results: Phytochemical profiling via HPLC and GC–MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 µg/g), vanillic acid (191.98 µg/g), and succinic acid (724.73 µg/g). The extracts exhibited robust antioxidant activity and dose-dependent cytotoxicity, reducing cell viability to as low as 5.60% after 72 h. Molecular analysis through Reactome pathway enrichment and expression profiling of 46 genes demonstrated that L. deliciosus drives cancer cells into a metabolic impasse by reversing the Warburg effect. Key findings include the significant downregulation of glycolytic genes like SLC2A1/GLUT1 (−12.34) and HK2 (−1.71), alongside the repression of mitochondrial TCA cycle regulators such as IDH1 (−17.81) and OGDH (−2.54). This metabolic collapse triggered G0/G1 phase cell cycle arrest and induced apoptosis. Conlusions: These results align with international benchmarks for Lactarius species while providing novel insights into the metabolic reprogramming mechanism. The results obtained in this study highlight that L. deliciosus emerges as a promising natural agent for therapeutic strategies targeting cancer bioenergetics. Full article

Pecan nutshells (PNS), once considered agricultural waste, are now recognized as a sustainable source of natural antioxidants with potential therapeutic benefits against oxidative stress-related diseases. This narrative review synthesized evidence from the last decade, including predominantly in vitro and in vivo studies, with limited clinical evidence. PNS are particularly rich in polyphenols (gallic acid, ellagic acid, vanillic acid, catechins), with phenolic and flavonoid concentrations reported to be 5–20 times higher than those in the edible kernels. Their antioxidant actions involve free radical scavenging, metal chelation, enhancement of enzymatic defenses, and modulation of redox signalling. Preclinical findings suggest protective roles in cardiovascular disease, diabetes, neurodegeneration, and cancer, mediated through reduced lipid peroxidation, improved glucose metabolism, neuroprotection, and anticarcinogenic activity. However, variability in extraction methods, cultivar differences, and bioavailability issues remain major challenges. Standardized clinical studies are needed to validate the therapeutic potential of PNS as a sustainable antioxidant source. Full article

Polyphenols are key dietary bioactive compounds, reducing oxidative stress and neurodegeneration. This study investigated the in vitro antioxidant and neuroprotective potential of some edible fruits (apricots, plums, figs) and vegetable (parsley) extracts related to their phytochemical profile. Plum extract exhibited the strongest antioxidant capacity (ABTS IC₅₀ 1.733 ± 0.079 mg/g; DPPH IC₅₀ 1.593 ± 0.069 mg/g; FRAP 23.161 ± 1.094 mM Fe²⁺), linked to its high chlorogenic and caffeic acids content. Parsley displayed the most potent AChE inhibition (IC₅₀ 0.825 ± 0.026 mg/g), associated with an elevated flavonoids level (TFC 12.874 ± 0.534 mg QE/g) and the presence of ferulic and vanillic acids. Apricot was characterized by notable gallic, syringic, and chlorogenic acids, supporting moderate neuroprotective potential. Figs showed weaker radical scavenging ability but provided a balanced profile of protocatechuic, caffeic, and syringic acids. Correlation analysis revealed specific compound–activity associations, including syringic and vanillic acids with DPPH scavenging capacity, p-coumaric acid with TPC, and gallic/ferulic acids with AChE inhibition. Effect-directed HPTLC confirmed chlorogenic acid as a major contributor to the antioxidant capacity. To our knowledge, this is the first study to comparatively integrate spectrophotometric antioxidant assays, UHPLC-based quantitative phenolic profiling, effect-directed HPTLC bioautography, and AChE inhibition analysis across three edible fruits and one vegetable frequently co-consumed in Mediterranean-type diets, enabling a cross-species compound–activity correlation framework. These species exhibit distinct but complementary phytochemical and biofunctional profiles. Their combined use may support the formulation of functional foods with synergistic antioxidant and neuroprotective benefits. Full article

This study evaluated the effect of freezing and frozen storage at three temperatures (−20, −30, −40 °C) on hop (Humulus lupulus L.) secondary metabolites and antioxidant capacity. These temperatures were selected based on the glass transition temperature (T_g’) of the maximally freeze-concentrated matrix. Cones were analyzed after freezing (t₀) and up to 360 days (t₃₆₀) by high-performance liquid chromatography with ultraviolet diode-array detection (HPLC-UV/DAD) for bitter acids, prenylflavonoids and phenolic acids, and by the Folin–Ciocalteu, ABTS the radical cation scavenging assay (ABTS) and the ferric-reducing antioxidant power assay (FRAP) assays for total phenolic content and antioxidant activity. Confocal laser scanning microscopy (CLSM) at t₃₆₀ was used to relate microstructural damage to metabolite retention. Freezing at −40 °C ensured the highest retention of bitter acids, phenolic acids (gallic, syringic, vanillic, caffeic, chlorogenic), and antioxidant capacity, whereas xanthohumol and 8-prenylnaringenin reached their maximum levels at −30 and −20 °C, respectively. During frozen storage, changes in metabolite profiles were mainly driven by storage time rather than temperature; over 360 days, α-acids, colupulone, xanthohumol and selected phenolic acids increased, while most other compounds declined. Multivariate analysis and CLSM elucidated the relationships between process conditions, tissue structure and metabolite profiles, enabling the selection of freezing and storage temperatures to optimally preserve different targets of hop bioactives and overall indicating −40 °C as the most effective. Full article

PET biodegradation remains limited due to its intrinsic properties—high crystallinity, hydrophobicity, and strong chemical stability. These characteristics lead to extremely slow degradation rates and contribute to PET’s persistence in the environment. Understanding how microorganisms respond at the molecular level when exposed to such a recalcitrant polymer is therefore essential. Living organisms express genes in response to their needs during development. When microbes are under critical conditions, such as when contaminants are present, they express genes encoding specific enzymes that attack the pollutant. In this study, a fungus isolated from the infected fruit of the plant Randia monantha was identified as Aspergillus terreus. It was tested for polyethylene terephthalate (PET) degradation, and the fungus Aspergillus nidulans was evaluated due to its previously reported recombinant cutinases for PET degradation. A microplastic polyethylene terephthalate (PET-MP) particle size of <355 μm for degradation was established, and a PET weight loss of 1.62% for A. nidulans and 1.01% for A. terreus was found. Additionally, the degradation of PET was confirmed by FTIR and SEM. This study also compares the transcriptomic profiles of Aspergillus nidulans and Aspergillus terreus during cultivation with PET-MP residues, which serve as a replacement for the carbon source. We present the first evidence of chitinase overexpression during direct exposure of PET to Aspergillus fungi. Interestingly, chitinase expression was detected in the crude extracts of A. nidulans and A. terreus during culture in the presence of PET residues, which replaced the carbon source. The chitinase produced by each fungus has a similar molecular weight of approximately 44 kDa. Chitinase activity was monitored over a 14-day cultivation period; from day 2, chitinase activity was detected in both cultures and continued to increase until day 14, when the highest values reported in this work were 24.88 ± 4.17 U mg⁻¹ and 10.41 ± 0.47 U mg⁻¹ for A. nidulans and A. terreus, respectively. Finally, we proposed a pathway for PET degradation by Aspergillus fungi that involves mycelial adherence and the secretion of hydrophobins, followed by the production of intermediates and monomers via esterase hydrolysis, and ultimately, the entry of monomers to the ethylene glycol (EG) and terephthalic acid (TPA) pathways, further suggesting these Aspergillus as candidates to produce valuable compounds under these conditions, such as muconic acid, gallic acid, and vanillic acid. Full article

The aim of the present study was to characterize the phenolic profile of hydroethanolic (EAEE) and ethyl acetate (EAAE) extracts of Echium asperrimum and to evaluate their antibacterial, antioxidant, anti-Alzheimer-related (cholinesterase inhibitory) activity, and antiproliferative activities. The DPPH radical scavenging activity of EAEE and EAAE showed IC₅₀ values of 32.53 ± 1.25 and 97.85 ± 2.31 µg/mL, respectively. In addition, both extracts exhibited phosphomolybdenum reduction capacity, with A_0.50 values of 61.60 ± 2.97 µg/mL for EAEE and 23.20 ± 1.55 µg/mL for EAAE. Acetylcholinesterase and butyrylcholinesterase inhibition assays revealed IC₅₀ values comparable to the reference compound galantamine. Both extracts also showed antimicrobial activity against Gram-positive and Gram-negative bacterial strains. LC-ESI-MS/MS analysis indicated that p-coumaric acid (5.12 mg/g), vanillic acid (11.6 mg/g), hydroxybenzaldehyde (3.82 mg/g), and gentisic acid (1.66 mg/g) were the major phenolic constituents of EAAE, whereas p-coumaric acid (0.13 mg/g), salicylic acid (0.141 mg/g), sinapic acid (0.20 mg/g), and trans-ferulic acid (0.20 mg/g) predominated in EAEE. Furthermore, EAAE exhibited dose-dependent antiproliferative activity at concentrations of 50 and 100 µg/mL, with an IC₅₀ value of 83.09 ± 6.50 µg/mL. Taken together, these findings suggest that E. asperrimum represents a promising source of bioactive compounds with potential relevance for future pharmaceutical and nutraceutical research. Full article

Hazelnut (Corylus avellana L.) shells, typically discarded as agro-industrial by-products, represent a potentially valuable source of bioactive polyphenolic compounds with significant antioxidant properties. This study aimed to evaluate and compare the polyphenol composition and antioxidant capacity of the kernels and shells of two hazelnut varieties, ‘Rimski’ and ‘Istarski duguljasti’. High-intensity ultrasound-assisted extraction (UAE) was applied to enhance the recovery of bioactive compounds under optimized conditions (80% ethanol, high amplitude, and 25 min treatment). The extracts were analyzed for total polyphenols, total flavonoids, total non-flavonoids, and individual phenolic compounds. Hazelnut shells exhibited significantly higher levels of total polyphenols, flavonoids, and antioxidant capacity compared to kernels. The dominant individual polyphenolic compounds identified in the shell were kaempferol, gallic acid, naringin, rutin trihydrate, quercetin-3-glucoside, chlorogenic acid, quercetin, ferulic acid, rosmarinic acid, and vanillic acid. Application of UAE notably improved extraction efficiency and overall yield compared to conventional extraction methods. The findings underscore hazelnut shells as a nutritionally and functionally valuable by-product and confirm UAE as a green, efficient extraction technique. These results provide a strong basis for developing high-value-added products for the cosmetic, pharmaceutical, and food industries, thereby supporting circular bioeconomy and sustainable chemistry principles. Full article