Search Results (130)

Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL⁻¹). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article

Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha (ER-α), and HER2. Using a robust 3D-QSAR model (R² = 0.86; Q²_LOO = 0.86) built from 52 steroidal structures, we identified molecular features associated with high anticancer potential, specifically increased polarizability and reduced electronegativity. From a virtual library of 271 DFT-optimized analogs, 31 compounds were selected based on predicted potency (pIC₅₀ > 7.0) and screened via molecular docking against PR (PDB 2W8Y), HER2 (PDB 7JXH), and ER-α (PDB 6VJD). Seven candidates showed strong binding affinities (ΔG ≤ −9 kcal/mol for at least two targets), with Estero-255 emerging as the most promising. This compound demonstrated excellent conformational stability, a robust hydrogen-bonding network, and consistent multitarget engagement. Molecular dynamics simulations over 100 nanoseconds confirmed the structural integrity of the top ligands, with low RMSD values, compact radii of gyration, and stable binding energy profiles. Key interactions included hydrophobic contacts, π–π stacking, halogen–π interactions, and classical hydrogen bonds with conserved residues across all three targets. These findings highlight Estero-255, alongside Estero-261 and Estero-264, as strong multitarget candidates for further development. By potentially disrupting the PI3K/AKT/mTOR signaling pathway, these compounds offer a promising strategy for overcoming resistance in hormone-driven breast cancer. Experimental validation, including cytotoxicity assays and ADME/Tox profiling, is recommended to confirm their therapeutic potential. Full article

Background/Objectives: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. Methods: Fifteen derivatives were created through photochemical cyclization and quaternization of the triazole core. The compounds were tested for AChE and BChE inhibition. They showed greater potency and selectivity toward BChE. Results: The most potent compound, derivative 14, inhibited BChE with an IC₅₀ of 98 nM, while derivative 9 also displayed significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC₅₀ = 0.66 µM). Molecular docking revealed that triazolinium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds 9 and 11, including low mutagenicity and moderate CNS permeability. Conclusions: These findings highlight the potential of new charged triazolinium salts as peripherally selective cholinesterase inhibitors with additional anti-inflammatory potential. Full article

Breast cancer treatments, such as chemotherapy, radiation, and surgery, often face significant limitations, highlighting the need for more effective and targeted therapies. Here, we investigate the potential of 266 nm laser irradiation of chlorpromazine as a novel approach to develop new antitumoral compounds. We identify six chlorpromazine photocompounds with masses in the range of 178–334 u, along with several dimeric compounds with masses between 566 and 600 u, using an HPLC-MS. In silico approaches assess their pharmacokinetic and pharmacodynamic properties while comparing their toxicity with the parent compound. Molecular docking simulations indicate that some photoproducts have a low estimated free energy of binding to cancer-related targets, suggesting enhanced therapeutic potential compared to chlorpromazine. Additionally, ADME-Tox predictions indicate that these photoproducts may have pharmacokinetic and toxicity profiles similar to chlorpromazine. Overall, this study highlights that laser-generated chlorpromazine photoproducts exhibit enhanced biological activity to breast cancer-related targets compared to chlorpromazine while maintaining a similar ADME-Tox profile. Full article

Cancer remains a major global public health concern, driving the need for innovative therapeutic agents with intensified efficacy and safety. Growth factor receptors (GFRs), often overexpressed in cancer cells and critical in regulating cell proliferation, survival, and tumor progression, represent key targets for cancer therapy. Halophytic plants like Salicornia spp. are known for their diverse bioactive compounds with notable pharmacological properties. This study comprehensively evaluated the anti-cancer potentials of phytochemicals derived from Salicornia herbacea and Salicornia brachiata using molecular docking and ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) profiling. A total of 37 bioactive compounds from Salicornia spp. were screened against HER1, HER2, and HER4 receptors. Among them, 3,5-di-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, myricetin, quercetin, stigmasterol, kaempferol, isorhamnetin, rhamnetin, and hesperitin featured strong predicted binding affinities to the HER1, HER2, and HER4 growth factor receptors, comparable to those of standard anti-cancer drugs such as gefitinib and dovitinib. Further pharmacokinetic assessments, including bioavailability and toxicity analyses, identified compounds with favorable drug-likeness properties and minimal toxicity risks, except for myricetin and quercetin. These findings underscore the potential of Salicornia-derived phytochemicals as promising candidates for the development of safe, novel, and effective anti-cancer agents targeting GFRs, contributing to the advances in precision oncology, pending further validation through in vitro and/or in vivo experiments. Full article

Background: Ovarian cancer is a major challenge in oncology due to high mortality rates, especially in advanced stages, despite current therapeutic approaches relying on chemotherapy and surgery. The search for novel therapeutic strategies is driven by the need for more effective treatments. This study focuses on novel xanthone derivatives modified with a morpholine ring, aiming to improve anticancer efficacy. Methods: In silico studies were conducted using ProTox III and SwissADME databases to assess the toxicity and ADME properties of the synthesized compounds. Molecular changes in cellular stress-related genes were investigated through qPCR in two ovarian cancer cell lines (TOV-21G and SKOV-3) following treatment with the compounds. Results: In silico analyses predicted high gastrointestinal absorption and blood–brain barrier permeability for the derivatives. Compounds exhibited varying toxicity and metabolic profiles. qPCR revealed significant alterations in genes related to antioxidant enzymes, molecular chaperones, and xenobiotic metabolism, indicating potential mechanisms of action and cellular responses to the compounds. Conclusions: The study demonstrates the potential of novel xanthone derivatives as promising candidates for ovarian cancer therapy, with implications for enhancing therapeutic efficacy and addressing drug resistance. Further research is warranted to elucidate the precise mechanisms underlying the observed effects and to develop tailored treatment strategies leveraging these agents. Full article

Background: Malaria remains a significant global health burden, particularly in sub-Saharan Africa, accounting for high rates of illness and death. The growing resistance to frontline antimalarial therapies underscores the urgent need for novel drug targets and therapeutics. Bromodomain-containing proteins, which regulate gene expression through chromatin remodeling, have gained attention as potential targets. Plasmodium falciparum bromodomain protein 1 (PfBDP1), a 55 kDa nuclear protein, plays a key role in recognizing acetylated lysine residues and facilitating transcription during parasite development. Methods: This study investigated ex vivo PfBDP1 gene mutations and identified potential small molecule inhibitors using computational approaches. Malaria-positive blood samples were collected. Genomic DNA was extracted, assessed for quality, and amplified using PfBDP1-specific primers. DNA sequencing and alignment were performed to determine single-nucleotide polymorphism (SNP). Structural modeling used the PfBDP1 crystal structure (PDB ID: 7M97), and active site identification was conducted using CASTp 3.0. Virtual screening and pharmacophore modeling were performed using Pharmit and AutoDock Vina, followed by ADME/toxicity evaluations with SwissADME, OSIRIS, and Discovery Studio. GROMACS was used for 100 ns molecular dynamics simulations. Results: The malaria prevalence rate stood at 12.24%, and the sample size was 165. Sequencing results revealed conserved PfBDP1 gene sequences compared to the 3D7 reference strain. Virtual screening identified nine lead compounds with binding affinities ranging from −9.8 to −10.7 kcal/mol. Of these, CHEMBL2216838 had a binding affinity of −9.9 kcal/mol, with post-screening predictions of favorable drug-likeness (8.60), a high drug score (0.78), superior pharmacokinetics, and a low toxicity profile compared to chloroquine. Molecular dynamics simulations confirmed its stable interaction within the PfBDP1 active site. Conclusions: Overall, this study makes a significant contribution to the ongoing search for novel antimalarial drug targets by providing both molecular and computational evidence for PfBDP1 as a promising therapeutic target. The prediction of CHEMBL2216838 as a lead compound with favorable binding affinity, drug-likeness, and safety profile, surpassing those of existing drugs like chloroquine, sets the stage for preclinical validation and further structure-based drug design efforts. These findings are supported by prior experimental evidence showing significant parasite inhibition and gene suppression capability of predicted hits. 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

Background/Objectives: Since the emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of compounds with antiviral potential from medicinal plants has been extensively researched. This study aimed to investigate plant metabolites with in vitro inhibitory potential against SARS-CoV-2 targets, including 3CL_pro, PL_pro, Spike protein, and RdRp. Methods: A systematic review was conducted following PRISMA guidelines, with literature searches performed in six electronic databases (Scielo, ScienceDirect, Scopus, Springer, Web of Science, and PubMed) from January 2020 to February 2024. Computational analyses using SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were performed to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as other medicinal chemistry parameters of these compounds. Results: A total of 330 plant-derived compounds with inhibitory activities against the proposed targets were identified, with compounds showing IC₅₀ values as low as 0.01 μM. Our findings suggest that several plant metabolites exhibit significant in vitro inhibition of SARS-CoV-2 targets; however, few molecules exhibit drug development viability without further adjustments. Additionally, after these evaluations, two phenolic acids, salvianic acid A and protocatechuic acid methyl ester, stood out for their potential as candidates for developing antiviral therapies, with IC₅₀ values of 2.15 μM against 3CL_pro and 3.76 μM against PL_pro; respectively; and satisfactory in silico drug-likeness and ADMET profiles. Conclusions: These results reinforce the importance of plant metabolites as potential targets for antiviral drug discovery. Full article

Background: Prostate cancer is the most common cancer in men, especially after the age of 50. It is a malignant disease that is increasing due to the increased life expectancy of the world population. Its development and progression are dependent on androgenic stimulation. Objectives: This study aimed to identify potential inhibitors with anti-prostate cancer activity through the application of chemoinformatics tools, exploring the Princeton (~1.2 million compounds) and Zinc Drug (~175 million compounds) databases. Methods: The methodology used several computational techniques, such as ROCS (Rapid Chemical Structure Superposition) and EON (Electrostatic Potential Screening), predictions of pharmacokinetic and toxicological properties, molecular docking, synthetic accessibility, biological activity, and molecular dynamics. Results: At the end of all these virtual screening steps, the study resulted in four promising potential candidates for the treatment of prostate cancer: the molecules ZINC34176694, ZINC03876158, ZINC04097308, and ZINC03977981, which exhibited all the desirable pharmacokinetic parameters (ADME/Tox) for a potential drug. Conclusions: Docking and molecular dynamics studies demonstrate stability and interaction with the androgen receptor of the selected compounds, showing them to be promising candidates for the development of new drugs. Full article

The prostaglandin E2 receptor EP3 is emerging as a promising therapeutic target in cardiovascular diseases because of its involvement in vascular inflammation, platelet aggregation, and vasoconstriction. However, selective EP3 ligands with validated biological activities are scarce. In this study, we combined computational and experimental strategies to identify and validate novel EP3 receptor ligands with therapeutic potential. We implemented a high-throughput, structure- and ligand-based virtual screening pipeline, enabling efficient exploration of approved drugs and natural compounds from DrugBank and FooDB libraries. Top-scoring candidates were prioritised based on binding energy and pharmacophoric similarity. Selected hits were subjected to in silico ADME/Tox profiling using QikProp to identify molecules with favourable pharmacokinetic and safety parameters. TUCA, masoprocol, and pravastatin sodium have emerged as lead candidates and were validated in vitro using endothelial migration and platelet aggregation assays. TUCA exhibited the most consistent inhibitory effect on endothelial migration, whereas masoprocol and hydrocortisone significantly reduced platelet aggregation. These findings establish a multidimensional workflow for the rational identification of EP3 ligands and support their potential use in cardiovascular therapeutics. Full article

Oleanolic acid derivatives, specifically lactones (2–8) and bromolactones (9–14), were synthesised and evaluated for their cytotoxic, antioxidant, and pharmacokinetic profiles. The compounds were characterised using molecular docking simulations targeting the 1M17 protein, representing the EGFR tyrosine kinase domain. Compound 6 emerged as the most promising candidate, demonstrating strong interactions with residues critical for EGFR activity, such as LYS 721 and ASP 831. Biological assays revealed that compounds 6, 2, and 10 exhibited IC₅₀ values across various cancer cell lines in the micromolar range, with a favourable Selectivity Index. Antioxidant activity assays (CUPRAC and DPPH) highlighted compound 7 as the most substantial electron donor and compound 10 as the most influential radical scavenger. ADMETox analysis confirmed the favourable pharmacokinetic and safety profiles of the derivatives. These findings underscore the potential of the selected oleanolic acid derivatives as drug candidates for targeted cancer therapies, offering cytotoxic and antioxidant benefits. Despite their promising cytotoxic and antioxidant activities, translating oleanolic acid derivatives to clinical applications remains challenging due to their bioavailability and metabolic stability. Our findings highlight compound 6 as a leading candidate with enhanced activity, providing a foundation for further optimising and developing EGFR-targeted anticancer therapies. Full article

Background/Objectives: Montelukast (MLK), a leukotriene receptor antagonist, has been associated with neuropsychiatric side effects. This study aimed to rationally modify MLK’s structure to reduce these risks by optimizing its interactions with dopamine D2 (DRD2) and serotonin 5-HT1A receptors using computational molecular simulation techniques. Methods: A library of MLK derivatives was designed and screened using structural similarity analysis, molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and ADME-Tox predictions. Structural similarity analysis, based on Tanimoto coefficient fingerprinting, compared MLK derivatives to known neuropsychiatric drugs. Docking was performed to assess initial receptor binding, followed by 100 ns MD simulations to evaluate binding stability. MM/PBSA calculations quantified binding affinities, while ADME-Tox profiling predicted pharmacokinetic and toxicity risks. Results: Several MLK derivatives showed enhanced DRD2 and 5-HT1A binding. MLK_MOD-42 and MLK_MOD-43 emerged as the most promising candidates, exhibiting MM/PBSA binding free energies of −31.92 ± 2.54 kcal/mol and −27.37 ± 2.22 kcal/mol for DRD2 and −30.22 ± 2.29 kcal/mol and −28.19 ± 2.14 kcal/mol for 5-HT1A, respectively. Structural similarity analysis confirmed that these derivatives share key pharmacophoric features with atypical antipsychotics and anxiolytics. However, off-target interactions were not assessed, which may influence their overall safety profile. ADME-Tox analysis predicted improved oral bioavailability and lower neurotoxicity risks. Conclusions: MLK_MOD-42 and MLK_MOD-43 exhibit optimized receptor interactions and enhanced pharmacokinetics, suggesting potential neuropsychiatric applications. However, their safety and efficacy remain to be validated through in vitro and in vivo studies. Until such validation is performed, these derivatives should be considered as promising candidates with optimized receptor binding rather than confirmed safer alternatives. Full article

Background/Objectives: pentane polyene antibiotic Roseofungin produced by actinomycetes possessing wide range of antimicrobial activity. Methods: The structure of novel polyene antibiotic Roseofungin was confirmed through FTIR, H¹ nuclear magnetic resonance, and high-performance liquid chromatography analysis with a mass detector. The substance pharmaco-technological parameters were evaluated. Additionally, the in silico modelling of various physicochemical parameters and biological activities was performed using validated open-access software tools such as ProTox3, SwissADME, and ADMET SAR1. The evaluation of its toxicological profile was also investigated in vivo. Results: The Roseofungin exhibits potential risks in certain categories, including immunotoxicity, respiratory toxicity, and nephrotoxicity, as predicted in silico. However, Roseofungin shows a relatively safe profile with regard to hepatotoxicity, neurotoxicity, and mutagenicity, along with lower risks of carcinogenicity and cytotoxicity in silico. The analysis of body weight dynamics after Roseofungin exposure in mice revealed no statistically significant differences among the experimental groups. Similarly, in the absolute or relative weights of internal organs across the experimental groups after Roseofungin treatment, no significant differences were observed in vivo. Roseofungin appears as a light-yellow hygroscopic powder with a specific odour, possessing the ability to settle and classified as a light powder. The particles are lamellar crystals ranging in size from 3 μm to 6 μm, and the molecules generate electrostatic tension between themselves. The pharmaco-technological parameters of Roseofungin were comprehensively studied. Conclusions: The experimental data obtained provide a foundation for further pharmaceutical development of new drugs containing the original Roseofungin. Full article

The world today is being ravaged by the emergence and re-emergence of microbial infections caused by antimicrobial-resistant strains, brought about primarily by the frequent and perhaps unnecessary use of antimicrobial agents. A need therefore arises to develop new antimicrobial drugs that can combat these pathogens resistant to currently available antibiotics. This present study has adopted a multi-enzyme in silico approach in evaluating new 2-pyrazolines as antimicrobial agents, targeting and aiming to inhibit three pivotal enzymes in the bacteria’s life cycle. A library of 2-pyrazolines was tailored to achieve the desired activity. The library of compounds and amoxicillin, a standard antimicrobial drug, were docked into the molecular target enzymes. They were also subjected to toxicity and drug-likeness tests, using PROTOX and swissADME, respectively. A moderate toxicity profile was indicated, as more than 90% of the ligands were in ProTox class 4. The majority exhibited advantageous ADME characteristics. A significant number of them demonstrated a binding affinity for the target proteins that was stronger than both the native ligand and the binding affinity of amoxicillin. Ligands 30, 20, and 8 are the notable ones across all target enzymes. These results suggest that these novel ligands may be powerful inhibitors, particularly when it comes to interfering with the formation of bacterial cell walls, folic acid, and nucleotide metabolism. Additional in vivo and in vitro research is required to confirm these results and evaluate their therapeutic potential. Full article