In silico pharmacology最新文献

{"title":"Computational exploration of aphrodisiac potential: identifying inhibitors from <i>Tribulus terrestris L</i>., and <i>Securidaca longepedunculata</i> targeting human phosphodiesterase 5.","authors":"Sikiru Akinyeye Ahmed, Ali Agaka Aremu, Muhammad Shafiq, Zaheer Ul-Haq","doi":"10.1007/s40203-025-00402-9","DOIUrl":"https://doi.org/10.1007/s40203-025-00402-9","url":null,"abstract":"<p><p>Impotence, also referred to as Erectile Dysfunction (ED), is a sexual health condition that affects a large number of men globally. The Food and Drug Administration (FDA) recommends Sildenafil citrate (Viagra®, Pfizer, New York, NY, USA) as a treatment for erectile dysfunction. Regretfully, heart failure, headaches, dizziness, blurred vision, irregular heartbeat, dyspepsia, and priapism have been reported as the main adverse effects of using Sildenafil citrate. Additionally, the cost is also exorbitant. Recent records suggest that certain compounds derived from phytochemical sources possess aphrodisiac qualities and can successfully treat erectile dysfunction without causing significant side effects. Thus, the focus of this work is to computationally investigate drug-target binding affinities and interactions at atomic levels using in silico techniques such as molecular docking, ADMET analysis, and molecular dynamics simulation. A total of 12 reported compounds (including one registered drug, which was used as a standard) exhibiting aphrodisiac qualities were docked with the crystal structures of the Human Phosphodiesterase 5 enzyme (PDB IDs: 1UDT, 1UHO, and 2CHM). When compared to the standard, all 11 compounds demonstrated good binding geometry and binding affinity scores. Of the 11 compounds selected for the best possible posing with the receptor, 6 satisfied Lipinski's rule of five. Following the completion of the ADMET studies, it was found that TanF (5-<i>p</i>-coumaroylquinic), TanI (Harmane), and XanA (1,3,6-trihydroxy-2,5-dimethoxyxanthone) had better pharmacokinetic properties than the standard. Molecular dynamics simulations and free energy calculations were used to determine the relative stability of the selected three potential compounds. The comprehensive results confirm that TanF, TanI, and XanA are more suitable candidates for the treatment of erectile dysfunction than the current medication, Sildenafil citrate. These findings suggest that natural product-derived compounds may serve as safer and more effective alternatives for erectile dysfunction therapy.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00402-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"113"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring capsaicin as a multi-target agent for osteoporosis through computational insights.","authors":"Mazumder Adhish, Balaraman Madhan, I Manjubala","doi":"10.1007/s40203-025-00400-x","DOIUrl":"https://doi.org/10.1007/s40203-025-00400-x","url":null,"abstract":"<p><p>Osteoporosis remains a significant global health challenge, characterized by an imbalance between bone formation and resorption, leading to compromised skeletal integrity and increased fracture risk. Capsaicin, the primary bioactive component in chilli peppers, has garnered attention for its potential role in modulating bone health due to its multifaceted pharmacological properties. This study investigates the molecular mechanisms underlying capsaicin's influence on osteoporosis-related pathways using a computational approach. Bioinformatics analyses identified key hub targets and signaling pathways linked to capsaicin's therapeutic effects. Employing molecular docking and dynamic simulations, we assessed capsaicin's binding interactions with critical protein targets, providing detailed insights into its structural and energetic properties. Notably, capsaicin demonstrated specific interactions with inflammation-related mediators and matrix-degrading enzymes, highlighting its capacity to interfere with processes driving bone loss. The findings suggest that capsaicin exerts dual-action effects by attenuating inflammation and suppressing bone degradation, positioning it as a promising candidate for osteoporosis treatment. This research enhances our understanding of capsaicin's role in maintaining skeletal health and underscores its potential as a therapeutic agent. Furthermore, the study provides a robust framework for future preclinical studies to validate its efficacy and optimize its application in clinical settings for managing osteoporosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00400-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"112"},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effects of <i>Centella asiatica</i> compounds on myeloid cell leukemia 1 (MCL-1) in cancer: a computational study.","authors":"Cecilia Oluwamodupe, Olorunfemi Oyewole Babalola, Paul Olamide Ottu, Erinayo Tolulope Aladeteloye, Elizabeth Temilolaoluwa Mogaji, Elijah Olamide Olumodeji, Victor Richard Adekanle, Olusola Olalekan Elekofehinti","doi":"10.1007/s40203-025-00399-1","DOIUrl":"10.1007/s40203-025-00399-1","url":null,"abstract":"<p><p>Myeloid cell leukemia 1 (MCL-1), a crucial anti-apoptotic member of the B-cell lymphoma 2 (BCL-2) family, has been extensively documented to be overexpressed in a variety of cancers, where it is essential for fostering cancer cell survival and treatment resistance. Elevated levels of MCL-1 have been observed in hematological cancers, such as acute myeloid leukemia and multiple myeloma, as well as in multiple solid tumors. We therefore examined the potential inhibitory effects of <i>Centella asiatica</i> compounds on MCL-1 using a computational drug discovery approach. Molecular docking analyses, including Glide XP (extra precision) were performed to evaluate the binding affinities of the compounds against the prepared crystal structure of MCL-1 (PDB ID: 6FS1) within the Schrödinger Suites. Additionally, the binding free energies of the compounds were computed to assess their thermodynamic stability within the binding pocket. The physicochemical and pharmacokinetic properties of the identified compounds were analyzed based on Lipinski's Rule of Five (RO5), electrostatic potential distribution, and ADME predictions. Predictive models for MCL-1 inhibitors were developed using AutoQSAR to examine the drug-likeness and biological activity of the screened compounds. We found 12 hit compounds, most of which met the RO5 criteria and were in the suggested ADME parameter range. Additionally, the predicted pIC50 values for these compounds were promising, suggesting their potential as MCL-1 inhibitors. The results of this study offer insightful analysis for the rational design of new anticancer treatments aimed at MCL-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"111"},"PeriodicalIF":0.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of antihyperglycemic and cytotoxic properties of <i>Ficus racemosa</i> L. Fruit extract.","authors":"Ananta Swargiary, Manita Daimari, Akalesh K Verma","doi":"10.1007/s40203-025-00397-3","DOIUrl":"10.1007/s40203-025-00397-3","url":null,"abstract":"<p><p><i>Ficus racemosa</i> L. is a important medicinal plant in Assam, traditionally used by the Bodo tribe, who consume its fruit extract as a preventive remedy for diabetes. Despite its widespread ethnomedicinal use, scientific studies on <i>F. racemosa</i> remain limited, particularly regarding the isolation and identification of its bioactive antidiabetic constituents. The present study investigated the metal contents, phytocompounds, anti-diabetic, and cytotoxicity properties of <i>F. racemosa</i> fruits extract. The AAS and GC-MS methods were used to analyze the metallic and phytocompounds of the plant. Enzyme inhibition study was carried out following standard protocols. In silico drug-likeness properties of phytocompounds were performed using computer-aided tools. Docking and output visualization were performed in AutoDock vina and Discovery studio. Pharmacophore modeling and structural superimposition were carried out for lead molecules. GC-MS analysis of the <i>F. racemosa</i> fruit extract showed six compounds. The fruit extract was found to contain only trace levels of toxic elements, indicating its safety for therapeutic use. In vitro study showed minimal cytotoxicity of the plant extract. Biochemical enzyme assays showed potential α-amylase and α-glucosidase inhibitory property of <i>F. racemosa</i>. Plant extract showed better enzyme inhibitory property compared to standard inhibitor, acarbose (<i>P</i> ≤ 0.05). All six compounds showed favorable drug-likeness, with compound-3 displaying the strongest binding in docking studies. Pharmacophore features and structure superimposition revealed compound-3 as a pivot molecule. Both the invitro and in silico study revealed similar results showing <i>F. racemosa</i> extract as a strong inhibitor of α-amylase and α-glucosidase. Thus, the present study suggests that the <i>F. racemosa</i> fruits may be a potential source of antihyperglycemic agents.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"110"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico exploration of pyrocannabinoid interactions with key protein targets.","authors":"Giovanni A Ramirez, Tesfay T Tesfatsion, Monica K Pittiglio, Kyle P Ray, Andrew Westerkamp, Westley Cruces","doi":"10.1007/s40203-025-00391-9","DOIUrl":"10.1007/s40203-025-00391-9","url":null,"abstract":"<p><p>Cannabinoids, particularly those derived from cannabis, attract considerable attention in recent years for their therapeutic potential in treating various diseases and ailments. In this study, we identify cannabinoid byproducts that result from the combustion of cannabidiol-henceforth referred to as pyrocannabinoids-and employ molecular docking simulations to investigate their interactions with key protein targets implicated in different physiological processes. Specifically, we focus on peroxisome proliferator-activated receptor gamma, p21-activated kinase 1, CB1, CB2, and GPR119 proteins, elucidating the binding modes and affinities of pyrocannabinoid byproducts to these receptors. This investigation is done in collaboration with Real Isolates LLC. Our findings reveal diverse ligand-protein interactions, with some pyrocannabinoids displaying favorable binding energies and stable ligand-protein complexes. However, variations in binding affinities across different proteins underscore the complex pharmacological profiles of the pyrocannabinoids. Furthermore, the prediction of adsorption, distribution, metabolism, excretion and toxicity properties highlights both promising and concerning aspects of cannabinoid pharmacokinetics, emphasizing the need for thorough preclinical evaluation. Additionally, our investigation into potential metabolic sites using cytochrome P450 enzymes provides insights into cannabinoid metabolites. Overall, our study contributes to the understanding of pyrocannabinoid pharmacology and informs the rational design of pyrocannabinoid-based therapeutics. Further experimental validation is warranted to translate these findings into clinically relevant applications.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00391-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"109"},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking nature's antidiabetic potential: computer-aided discovery of α-amylase and α-glucosidase inhibitors in <i>Andrographis paniculata</i> leaves.","authors":"Ananta Swargiary, Manita Daimari, Mritunjoy Kumar Roy, Dulur Brahma","doi":"10.1007/s40203-025-00396-4","DOIUrl":"10.1007/s40203-025-00396-4","url":null,"abstract":"<p><p>The study aims to provide <i>in-vitro</i> evidence for the potential inhibition of α-glucosidase and α-amylase enzymes by five selected medicinal plants. The present study investigated the in vitro α-amylase and α-glucosidase inhibitory activity of <i>Andrographis paniculata</i> following standard protocols. GC-MS analysis was carried out to identify the bioactive compounds. Furthermore, molecular docking and MD simulation was carried out to understand the binding affinity of the <i>A. paniculata</i> compounds with the pancreatic enzymes. The crude extracts of plants showed a considerable α-amylase and α-glucosidase inhibitory activity. The IC₅₀ values of α-amylase and α-amylase inhibition was found to be 1.72 ± 0.03 mg/ml and 0.30 ± 0.01 mg/ml, respectively. Refence drug, acarbose also showed almost similar inhibitory activity. Eight probable phytocompounds were identified using GC-MS analysis. Compund-7 showed the strongest binding affinity with both the α-amylase and glucosidase enzymes. MD simulation study observed slightly more stable and compact structure of α-amylase-phytocompound structure compared to acarbose-protein complex. The study suggests that <i>A. paniculata</i> extracts have potential for managing hyperglycemia and type-2 diabetes mellitus. However, further research is required to confirm their efficacy and safety.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00396-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"108"},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico identification of phytoconstituents from <i>Capparis sepiaria</i> as interleukin-1 inhibitors for rheumatoid arthritis: molecular docking, ADMET profiling, and molecular dynamics simulation.","authors":"Darius R Martin, Antoinette Ajmal, Mervin Meyer, Abram M Madiehe","doi":"10.1007/s40203-025-00386-6","DOIUrl":"10.1007/s40203-025-00386-6","url":null,"abstract":"<p><p>In this study computational methods were used to explore the anti-inflammatory properties of <i>Capparis</i> (<i>C.</i>) <i>sepiaria</i> extracts; focusing on their activity against pro-inflammatory cytokine, interleukin-1 (IL-1). Molecular docking was performed on 18 <i>C. sepiaria</i> phytoconstituents using AutoDock VinaXB. The study identified five compounds (CIDs 8122, 33934, 605626, 638072, 5363269) with high affinity for IL-1. Notably, CID 638072 demonstrated superior binding affinity compared to standard controls such as thalidomide. Pharmacokinetic and toxicity profiles were assessed using SwissADME and pkCSM which showed that all these compounds met acceptable criteria as promising anti-inflammatory agents. Molecular dynamics simulations with GROMACS (version 2019) confirmed the stability and interaction dynamics of these compounds, which support the docking results. The findings validate the traditional medicinal use of <i>C. sepiaria</i> for the treatment of inflammation, suggesting that CID 638072 holds significant potential for further development into a natural anti-inflammatory therapeutic. This research provides clues for the therapeutic applications of <i>C. sepiaria</i>, advancing the search for effective natural remedies for the treatment of inflammation. Further experimental validation is necessary to transition this study from computational predictions to clinical applications.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"106"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl benzoyl hydrazide derivatives as potent inhibitors of the NS2B-NS3 protease and RNA-dependent RNA polymerase of the zika virus.","authors":"R P Yadav, N R Jena","doi":"10.1007/s40203-025-00395-5","DOIUrl":"https://doi.org/10.1007/s40203-025-00395-5","url":null,"abstract":"<p><p>The NS2B-NS3 protease and the RNA-dependent RNA polymerase (RdRp) of the Zika virus (ZIKV) are interlinked with viral genome replication. Therefore, inhibiting their activities would reduce the viral loads in patients. To identify molecules that can strongly bind to the substrate binding site of the NS2B-NS3 protease of the ZIKV, interactions of several aryl benzoyl hydrazide (ABH) derivatives (10b, 10c, 10g, 11p, and 11q) and some anti-influenza drugs (Zanamivir, Laninamivir, Baloxavir, Oseltamivir, Rimantadine, Peramivir, and Amantadine) with the ZIKV NS2B-NS3 protease are studied herein by using combined density functional theoretic, docking, molecular dynamics (100 ns MD simulations), and free-energy methods. Among these molecules, 11q binds strongly to the ZIKV protease with a ΔG_bind of about - 15.70 ± 2.30 kcal/mol. Its binding to the NS2B-NS3 protease is stronger than the anti-influenza drugs studied herein. Notably, the binding affinity of 11q is found to be approximately 4 kcal/mol more negative than that of SYC-1307, a known allosteric inhibitor of the ZIKV protease. 11q is also found to bind to the NTP and allosteric sites of the ZIKV RdRp. However, the binding of 11q to the NTP site of RdRp is preferred over that of the allosteric site. Interestingly, extending the simulation time to 500 ns did not alter the structure of 11q bound to both ZIKV protease and the NTP site of RdRp. However, 11q showed a higher affinity toward the NS2B-NS3 protease than the NTP site of RdRp. Computed ADMET parameters, Lipinski's rule of five, and binding affinities suggest that 11q would be a better drug candidate against ZIKV infections.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00395-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"107"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacophoric analogs of Savolitinib reveal promising inhibitors of the c-MET receptor tyrosine kinase for drug discovery: in silico investigation.","authors":"Lateef Adegboyega Sulaimon, Hameedah Ayanfunke Bamiji, Mercy Eshiet Akpekong, Toyyibat Adelola Asade, Usman Jamila Bashir, Damola Habeeb Adetunji, Ireoluwa Yinka Joel, Rahmat Adetutu Adisa, Titilola Aderonke Samuel, Ashraf Akintayo Akintola","doi":"10.1007/s40203-025-00394-6","DOIUrl":"https://doi.org/10.1007/s40203-025-00394-6","url":null,"abstract":"<p><p>The c-MET receptor tyrosine kinase has become a key focus for therapeutic intervention in various cancer types due to its crucial role in driving cancer progression and metastasis. While Savolitinib, a specific inhibitor of c-MET, has demonstrated promise in clinical trials, its limited availability within the body and the risk of developing resistance have prompted a quest for alternative inhibitors. In this research endeavor, we downloaded and screened a range of pharmacophoric analogs inspired by Savolitinib to explore new avenues for inhibiting c-MET. By delving into the molecular structure of Savolitinib and deciphering how it interacts with the c-MET kinase, we aimed to identify critical structural features and functional groups that could be modified to enhance its inhibitory efficacy and pharmacological properties. Employing computational modeling and pharmacokinetic assessments, this research strives to unveil novel analogs that may exhibit superior potency, selectivity, and overall drug-like attributes. Out of the 997 compounds screened, seventeen demonstrated binding energy values comparable to or greater than - 10.2 kcal/mol obtained for Savolitinib during the redocking experiment. Following a thorough evaluation via in silico ADMETox and drug-likeness prediction, two compounds, namely CID_134565115 and CID_153611202, emerged as promising candidates. They not only exhibited favorable binding energy values but also displayed a well-balanced profile concerning stability, drug-likeness and toxicity. In summary, both CID_134565115 and CID_153611202 demonstrated favorable binding energies and distinctive interaction patterns, surpassing the established Savolitinib. Although our computational study highlights the promising potential of these lead-like candidates in obstructing oncogenic c-MET signaling, further experimental investigations are necessary to verify and establish their preclinical relevance.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"104"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and toxicological profile in pharmaceutical bioprospecting of caryophyllene molecules using computational biology for therapeutic purposes.","authors":"André Nogueira Cardeal Dos Santos, José Ednésio da Cruz Freire, Andrelina Noronha Coelho-de-Souza","doi":"10.1007/s40203-025-00392-8","DOIUrl":"https://doi.org/10.1007/s40203-025-00392-8","url":null,"abstract":"<p><p>β-Caryophyllene, abundant in plants such as <i>Salvia rosmarinus</i>, <i>Cannabis sativa</i>, and <i>Hyptis crenata</i>, possesses various biological activities, including anti-inflammatory, analgesic, neuroprotective, and anticancer properties. However, its high lipophilicity and low stability in hydrophilic environments limit its therapeutic application. To overcome these limitations, the study aimed to bioprospect an molecular derivatives of caryophyllene with improved bioavailability using computational biology analyses. The Canonical SMILES of the molecules were obtained from PubChem and submitted to various servers for analysis of physicochemical, pharmacokinetic, and toxicological properties. Of the 60 identified molecular derivatives, only one met 44 selection criteria, including gastrointestinal absorption, plasma protein binding, metabolism by CYP₄₅₀ enzymes, and toxicological parameters. Comparisons between β-caryophyllene (βC) and caryophyllene-keto-epoxide (CKE) showed that CKE has better gastrointestinal absorption and lower affinity for plasma proteins, increasing the free fraction in the blood. Both compounds do not inhibit nor are they substrates for CYP₄₅₀ enzymes and exhibit good interaction with Caco-2 intestinal cells. CKE, with log P and log D within the desired range, demonstrated to be a more effective alternative in terms of bioavailability compared to βC. These results suggest that CKE can overcome the limitations of βC, offering better stability and bioavailability, thereby enhancing its therapeutic applications. However, further research is necessary to determine whether the primary therapeutic targets of βC remain the same for CKE and to evaluate the differences in therapeutic efficacy between them.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00392-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"105"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}