Search Results (280)

Anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL, and Mcl-1), are often overexpressed in cancer, which aids tumor growth and treatment resistance. As a result, these proteins are excellent candidates for novel anticancer drugs. Within this study a virtual library of betuline derivatives was built and screened for possible Bcl-2, Bcl-XL, and Mcl-1 inhibitors. For every target, molecular docking simulations were performed using two different engines (AutoDock Vina and Glide). The ligands that most frequently appeared among the top candidates were shortlisted after comparing the top-20 hits from both docking scoring functions. To assess binding stability, five of these promising compounds were chosen and run through 100 ns molecular dynamics (MD) simulations in complex with every target protein. Key persistent intermolecular contacts were identified from MD contact frequency histograms, and stability was evaluated using root-mean-square deviation (RMSD) profiles of protein–ligand complexes following equilibration. Additionally, Prime MM-GBSA binding energies (ΔG_bind) for the 15 docked complexes were computed, and ligand efficiency was reported. Two substances, BOxNaf1 and BT3, stood out among the screened derivatives as the most stable binders to all three Bcl-2 family targets according to the dual docking and MD analysis approach. When the MM-GBSA and RMSF/rGyr data are considered alongside docking and MD stability, BOxNaf1 and BOxPhCl1 emerge as the most compelling dual/multi-target candidates, whereas BT3, though MD stable, shows weaker MM-GBSA energetics and is retained as a lower-priority backup chemotype. Full article

Perovskia atriplicifolia Benth., a perennial aromatic plant widespread in Iran’s Sistan and Baluchestan region, is known for its essential oil composition, rich in aromatic and non-aromatic sesquiterpenes. To the best of our knowledge, limited information exists on the composition of its non-volatile extracts. Herein, the phytochemical investigation of the EtOH extract of P. atriplicifolia aerial parts was performed, guided by an analytical approach based on LC-(-)ESI/QExactive/MS/MS. This led to the identification of phenolics, flavonoids, diterpenes (mainly carnosic acid derivatives), and triterpenes. Structural elucidation was performed via NMR and HRMSMS analysis. Furthermore, considering the occurrence of diterpenes closely related to carnosic acid and carnosol, known for their antioxidant properties, the antioxidant activity of the extract (0.5–5.0 μg/mL) and selected pure compounds (0.5–25 μM; compounds 5, 7, 9, 10, 12, 16) was evaluated in Caco-2 intestinal cells, showing significant reduction in free radical levels. The quantitative results highlighted that the above cited compounds occurred in concentrations ranging from 1.73 to 520.21 mg/100 g aerial parts, with carnosol (12) exhibiting the highest concentration (520.21 mg/100 g aerial parts), followed by 1α-hydroxydemethylsalvicanol (9) (91.73 mg/100 g aerial parts) and carnosic acid (16) (88.16 mg/100 g aerial parts). Full article

Introduction: Malaria is a tropical disease caused by the parasite Plasmodium sp., which is considered a significant public health challenge, particularly in Africa. Among the species related to human infection, P. falciparum and P. vivax are known for their high incidence and pathogenicity. Despite several approved drugs in the treatment, the increase in resistance mechanisms is becoming increasingly prevalent, which makes the discovery of effective and safer drugs challenging. Thus, it is necessary to explore new mechanisms of action for the discovery of innovative antimalarial agents. Among the explored targets, proteases, especially subtilisin, have shown great promise in the development of new therapeutic options. Method: A narrative review was conducted using the main databases to provide critical information about the subtilisin to design antimalarial drugs. Results: Critical data were found about the isoforms of subtilisins, highlighting SUB1 and SUB2. SBDD approaches were able to show that compounds designed to target the catalytic Asp³⁷², His⁴²⁸, and Ser⁶⁰⁶, and other such Leu⁴⁶⁹, Gly⁴⁶⁷, and Asn⁵²⁰ against SUB1, presented critical results. In addition, quinoline, benzopyran, and triterpene derivatives and peptide inhibitors show their importance, and these scaffolds can be explored in further work. Conclusions: Considering the relevance of this target, this review provided insights into medicinal chemistry, the discovery of antimalarial drugs that act by inhibiting subtilisin, and promoted a promising initiative to combat malaria. Full article

Olive oil, a cornerstone of the Mediterranean diet, contains a saponifiable lipid fraction rich in oleic acid, and a non-saponifiable fraction composed of minor bioactive constituents such as squalene, vitamin E, oleuropein aglycone, hydroxytyrosol, oleocanthal, and oleacein, among other phenolic and triterpenic compounds. These components are well-documented for their cardiovascular, anti-inflammatory, antioxidant, and neuroprotective activities. This review explores the physiological relevance of olive oil lipids and their derivatives on cellular membranes and ion transport systems, by combining biochemical and electrophysiological insights. We discuss how oleic acid and its metabolites influence membrane lipid composition, modulate fluidity, and reorganize lipid rafts—key elements for the proper localization and function of ion channels. Additionally, we examine evidence showing that several olive oil components regulate ion channels such as TRP, potassium, calcium, and chloride channels, as well as other transporters, thereby influencing ionic homeostasis, oxidative balance, and signal transduction in excitable and non-excitable cells. By combining these findings, we propose a conceptual framework in which olive oil lipids and their derivatives act as multimodal regulators of bioelectrical signaling. By modulating cell membrane dynamics, these functional molecules help maintain cellular communication and homeostasis. This integrative view not only strengthens our understanding of olive oil’s health-promoting effects but also opens new avenues for targeting ion-regulatory mechanisms in metabolic, cardiovascular, and neurological diseases. Full article

Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among the five derivatives obtained, 3α,24-dihydroxy-30-oxolup-20(29)-en-28-oic acid (T1c) exhibited the highest activity, with an IC₅₀ value of 12.90 ± 0.1 µM against THP-1 cells. T1c significantly reduced cell viability in both acute lymphoblastic leukemia (CCRF-CEM, REH, JURKAT, and MOLT-4) and acute myeloid leukemia (THP-1) cell lines, inducing apoptosis after 48 h of treatment, while showing minimal cytotoxicity toward normal mononuclear cells (MNCs). In silico molecular docking studies were conducted against three key protein targets: BCL-2 (B-cell lymphoma 2), EGFR (epidermal growth factor receptor, tyrosine kinase domain), and FLT3 (FMS-like tyrosine kinase 3). The lowest binding energies (kcal/mol) observed were as follows: T1–BCL-2: −10.12, EGFR: −12.75, FLT3: −14.05; T1c–BCL-2: −10.23, EGFR: −14.50, FLT3: −14.07; T2–BCL-2: −11.59, EGFR: −15.00, FLT3: −14.03. These findings highlight T1c as a promising candidate in the search for anti-leukemic drugs which deserves further study. Full article

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, and triterpenes) isolated from 104 fungal strains across 33 genera. Sesquiterpenoids and diterpenoids constitute the predominant chemical classes, with Trichoderma, Aspergillus, Eutypella, and Penicillium being the most productive genera. These fungi were primarily sourced from distinct marine niches, including deep sea sediments, algal associations, mangrove ecosystems, and invertebrate symbioses. Notably, 57% of the 266 tested compounds exhibited diverse biological activities, encompassing anti-inflammatory, antibacterial, antimicroalgal, antifungal, cytotoxic effects, etc. The chemical diversity and biological activities of these marine fungal terpenoids underscore their value as promising lead compounds for pharmaceutical development. Full article

Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound 1), were isolated from the fruits of Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound 4) and a commercially available 28-O-β-D-glucopyranosyl hederagenin ester (compound 3), were evaluated for cytotoxicity and selectivity across a wide panel of human cancer cell lines (skin, prostate, gastrointestinal, thyroid, and lung). All four compounds exhibited dose- and time-dependent effects, with varying potency depending on the specific cancer type. The isolated bidesmosidic saponin (3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin 28-O-β-D-glucopyranosyl ester—compound 2) showed the strongest activity and selectivity, with an IC₅₀ = 6.52 μg/mL after 48 h incubation against WM793 melanoma, and almost no effect on normal HaCaT skin cells (IC₅₀ = 39.94 μg/mL). Multivariate analysis of the obtained data using principal component analysis (PCA) and hierarchical cluster analysis (HCA) supported the assumption that cytotoxicity is influenced by the type of compound, its concentration, and the intrinsic sensitivity of the cell line. Structure-activity observations between closely related hederagenin derivatives are also briefly presented. Full article

Due to the limited scientific exploration of Argania spinosa (L.) skeel husk, this study presents the first investigation of the metabolite profile of methanol and acetone extracts analyzed by liquid chromatography coupled with electrospray ionization and high-resolution multistage mass spectrometry (LC-ESI/HRMSMS). A total of 43 compounds, including hydroxycinnamic acid and flavonoid derivatives, saponins, and triterpenic acids, were identified, some of which have not been previously reported in this species. The total phenols (TPC) and flavonoids (TFC) content were spectrophotometrically determined. A multi-target approach was applied to investigate the antioxidant potential using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), β-carotene bleaching, and Ferric Reducing Ability Power (FRAP) tests. Carbohydrate hydrolyzing enzymes and lipase inhibitory activities were also assessed. The acetone extract exhibited the highest TPC and TFC values, resulting in being the most active in β-carotene bleaching test with IC₅₀ values of 26.68 and 13.82 µg/mL, after 30 and 60 min of incubation, respectively. Moreover, it was the most active against both α-glucosidase and α-amylase enzymes with IC₅₀ values of 12.37 and 18.93 µg/mL, respectively. These results pointed out that this by-product is a rich source of bioactive phytochemicals potentially useful for prevention of type 2 diabetes and obesity. Full article

This study revealed variations in the composition and in vitro antioxidant activity of proanthocyanidins, hydroxycinnamic acid derivatives, flavonols, anthocyanins, and triterpene compounds in small cranberry fruit samples collected from a bog-type natural habitat in Lithuania during intensive ripening of the fruit. The highest total amounts of identified flavonols were determined at the beginning of fruit ripening on September 10 (1232.84 ± 31.73 µg/g). The highest total amounts of proanthocyanidins (1.85 ± 0.02 mg EE/g, p < 0.05), anthocyanins (4096.79 ± 5.93 µg/g, p < 0.05), and triterpene compounds (8248.46 ± 125.60 µg/g, p < 0.05) were detected in small cranberry fruit samples collected in the middle of the ripening period (September 16–18). The most potent in vitro antiradical and reducing activity was found in extracts of small cranberry fruit collected on September 10 (95.25 ± 1.15 µmol TE/g and 159.26 ± 0.77 µmol/g, respectively). The strongest correlation was found between the total content of hydroxycinnamic acid derivatives in the small cranberry fruit samples and the in vitro reducing activity of their extracts (0.858, p < 0.01). Among the individual compounds, the strongest correlation was observed between the amounts of isoquercitrin and guaijaverin in V. oxycoccos fruit samples and the in vitro reducing activity as assessed by the CUPRAC method (0.844, p < 0.01 and 0.769, p < 0.05, respectively). Full article

Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm²). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms. Full article

Recent advances highlight the crucial role of the gut microbiota in human health and disease, with dietary components emerging as powerful modulators of microbial communities. This review synthesizes current evidence on the effects of olive-derived bioactive compounds, including polyphenols (e.g., hydroxytyrosol, oleuropein or tyrosol), triterpenes and other phytochemicals on gut microbiota composition and function. These compounds have been shown to enhance beneficial bacterial populations such as Lactobacillus and Bifidobacterium, reduce potentially pathogenic taxa, and promote the production of short-chain fatty acids and other health microbial metabolites, reinforcing intestinal barrier integrity. In vitro, in vivo, and clinical studies also reveal the potential of olive bioactives to ameliorate metabolic, inflammatory, and neurocognitive disorders through gut-microbiota-brain axis modulation. Despite promising results, key challenges remain, including interindividual microbiota variability, lack of standardized intervention protocols, and limited human clinical trials. Addressing these gaps through robust translational research could pave the way for microbiota-targeted, personalized nutritional strategies based on olive-derived compounds. Full article

This paper presents the influence of acetylation on the cytotoxic and antioxidant activity of natural triterpenes. Oleanolic acid, betulin, betulinic acid and other triterpenes have been modified to improve their pharmacological properties. Acylation of the hydroxyl group at the C-3 position showed significant changes in biological activity, in particular against cancer cell lines such as HeLa, A-549, MCF-7, PC-3 and SKOV-3, with the highest IC₅₀ results for acetyloleanolic acid (1b) and acetylbetulinic acid (4b). Docking results showed that all compounds tested demonstrated the ability to bind to pockets (C1–C5) of the p53 Y220 protein, obtaining different Vina score values. The strongest binding was observed for compound 2b in the C3 pocket (−10.1 kcal × mol⁻¹), while in the largest C1 pocket, the best result was achieved by compound 5b (−9.1 kcal × mol⁻¹). Moreover, antioxidant studies using the CUPRAC and DPPH tests showed significant differences in the mechanisms of action of the compounds depending on the structure. The analyses of ADMETox confirmed the favorable pharmacokinetic profile and low toxicity of most of the tested derivatives. The results suggest that acetylated triterpenes, especially 1b and 4b, have great potential as anticancer drug candidates, requiring further research on their cytotoxic activity and structural modifications. Full article

The use of plant extracts and the compounds isolated from them for the treatment of cancer is an area of active research, given their therapeutic potential. This work focused on evaluating the literature related to the antiproliferative activity of extracts obtained from plants of the genus Tabebuia and molecules isolated in vitro or in vivo. For the search, MeSH and DECS terms were employed in the PubMed, Scopus, and SciELO databases. Research has shown that plant extracts derived from plants of the genus Tabebuia exhibit potential applications in the search for new molecules with antiproliferative activity. Among the isolated molecules, the most evaluated correspond to β-lapachone (naphthoquinone); however, molecules with antiproliferative potential belonging to groups such as iridoids, flavonoids, quinones, furanonaphthoquinones, triterpenes, and polysaccharides have also been isolated and reported. Additionally, synthesized molecules have been evaluated on the basis of the modifications made to the structures of molecules isolated from the plant extracts to increase their activity, aiming to develop more potent antitumor agents for future clinical use. Full article

Phytochemical investigation of the methanol extract of Embelia parviflora Wall. Ex A. DC. leaves (Primulaceae family) led to the isolation of sixteen compounds including three sterols (1–3), one triterpene (4), four flavonoids (5–8), four megastigmanes (9–12), three phenolic compounds (13–15), and one furan derivative (16). Their chemical structures were determined based on ESI-MS and NMR spectral data. This is the first chemical study of E. parviflora. Compounds 3, 8–13, and 16 were found in the Embelia genus for the first time. Compounds 9–11, 13, and 16 represent the first isolation from the Primulaceae family. In the α-glucosidase activity assay, MeOH extract, compounds 4 and 5 strongly inhibited enzyme α-glucosidase activity. A molecular docking study revealed that compounds 4 and 5 showed different interactions with enzyme α-glucosidase. Full article