{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:57Z","timestamp":1785418557707,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kuwait University-Research Sector","award":["PC 01\/25"],"award-info":[{"award-number":["PC 01\/25"]}]},{"award":["PC 01\/25"],"award-info":[{"award-number":["PC 01\/25"]}],"id":[{"id":"https:\/\/ror.org\/021e5j056","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography\u2013mass spectrometry (GC\u2013MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein\u2013ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC\u2013MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for \u03b1-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions.<\/jats:p>","DOI":"10.3390\/ph19060834","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:36:56Z","timestamp":1779892616000},"page":"834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment and Density Functional Theory of Bioactive Compounds of Curcuma longa L. Root Responsible for Its Cardio-Protective and Anti-Cancer Activities"],"prefix":"10.3390","volume":"19","author":[{"given":"Ahmed","family":"Hemdan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Health Science Center, Kuwait University, Jabriya, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1551-5034","authenticated-orcid":false,"given":"Sylvester Nnaemeka","family":"Ugariogu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Health Science Center, Kuwait University, Jabriya, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashayer D.","family":"Althufairi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Health Science Center, Kuwait University, Jabriya, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-4032","authenticated-orcid":false,"given":"Naser F.","family":"Al-Tannak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Health Science Center, Kuwait University, Jabriya, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","unstructured":"Saleh, S. (2024, June 30). Causes of Death in Kuwait. Available online: https:\/\/www.statista.com\/statistics\/672389\/kuwait-share-of-deaths-by-major-cause."},{"key":"ref_2","unstructured":"World Health Organization (2024, June 30). Cardiovascular Diseases. Available online: https:\/\/www.who.int\/health-topics\/cardiovascular-diseases#tab=tab_3."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100438","DOI":"10.1016\/j.kjs.2025.100438","article-title":"A review on recent insight on cardiovascular diseases drug design using natural products and insilico studies","volume":"52","author":"Ugariogu","year":"2025","journal-title":"Kuwait J. Sci."},{"key":"ref_4","first-page":"16","article-title":"Anticolorectal Cancer Properties of Some Flavonoids and Terpenoids from African Propolis via Molecular Docking","volume":"5","author":"Ugariogu","year":"2022","journal-title":"South Asian Res. J. Nat. Prod."},{"key":"ref_5","first-page":"000233","article-title":"Preliminary Pharmaceutical Active Ingredient and Micronutrient Evaluation of the Leaf of Corchorus olitorius (Ahiahara)","volume":"4","author":"Ugariogu","year":"2020","journal-title":"Nat. Ayurvedic Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7656919","DOI":"10.1155\/2020\/7656919","article-title":"Biochemistry, Safety, Pharmacological Activities, and Clinical Applications of Turmeric: A Mechanistic Review","volume":"2020","author":"Ahmad","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fuloria, S., Mehta, J., Chandel, A., Sekar, M., Rani, N.N.I.M., Begum, M.Y., Subramaniyan, V., Chidambaram, K., Thangavelu, L., and Nordin, R. (2022). A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.820806"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sharifi-Rad, J., Rayess, Y.E., Rizk, A.A., Sadaka, C., Zgheib, R., Zam, W., Sestito, S., Rapposelli, S., Neffe-Skocin, K., and Zielin, D. (2020). Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01021"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111888","DOI":"10.1016\/j.biopha.2021.111888","article-title":"Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential","volume":"141","author":"Lebin","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Saleem, A., Akhtar, M.F., Sharif, A., Akhtar, B., Siddique, R., Ashraf, G.M., Alghamdi, B.S., and Alharthy, S.A. (2022). Anticancer, CardioProtective and Anti-Inflammatory Potential of Natural-Sources-Derived Phenolic Acids. Molecules, 27.","DOI":"10.3390\/molecules27217286"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100222","DOI":"10.1016\/j.prmcm.2023.100222","article-title":"Curcuma longa (Turmeric): Ethnomedicinal uses, phytochemistry, pharmacological activities and toxicity profiles\u2014A review","volume":"6","author":"Iweala","year":"2023","journal-title":"Pharmacol. Res.-Mod. Chin. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, T., Jin, J., Pu, F., Bai, Y., Chen, Y., Li, Y., and Wang, X. (2023). Cardioprotective effects of curcumin against myocardial ischemia\/reperfusion injury: A systematic review and meta-analysis of preclinical and clinical studies. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1111459"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155619","DOI":"10.1016\/j.phymed.2024.155619","article-title":"Cardioprotective effects of curcumin against diabetic cardiomyopathy: A systematic review and meta-analysis of preclinical studies","volume":"129","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cozmin, M., Lungu, I.I., Gutu, C., Stefanache, A., Duceac, L.D., \u0218oltuzu, B.D., Damir, D., Calin, G., Bogdan Goroftei, E.R., and Grierosu, C. (2024). Turmeric: From spice to cure. A review of the anti-cancer, radioprotective and anti-inflammatory effects of turmeric sourced compounds. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1399888"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00228-024-03764-9","article-title":"Curcumin as a complementary treatment in oncological therapy: A systematic review","volume":"81","author":"Gutsche","year":"2025","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kaur, K., Al-Khazaleh, A.K., Bhuyan, D.J., Li, F., and Li, C.G. (2024). A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities. Antioxidants, 13.","DOI":"10.20944\/preprints202403.1292.v1"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Amaroli, A., Panfoli, I., Bozzo, M., Ferrando, S., Candiani, S., and Ravera, S. (2024). The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management. Cancers, 16.","DOI":"10.3390\/cancers16142580"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6048","DOI":"10.1002\/ptr.8340","article-title":"Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials","volume":"38","author":"Jafari","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_19","first-page":"190","article-title":"In-vitro and in-silico determinations of HMG-CoA reductase inhibition potential of caffeic acid for therapeutics of hypercholesterolemia","volume":"12","author":"Heera","year":"2022","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.1021\/acsomega.2c07893","article-title":"In Silico Characterization of Withania coagulans Bioactive Compounds as Potential Inhibitors of Hydroxymethylglutaryl (HMG-CoA) Reductase of Mus musculus","volume":"8","author":"Azmi","year":"2023","journal-title":"ACS Omega"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.26650\/EurJBiol.2023.1178214","article-title":"In Silico Approach for Identification of PI3K\/mTOR Dual Inhibitors for Multiple Myeloma Treatment","volume":"82","author":"Masalaci","year":"2023","journal-title":"Eur. J. Biol."},{"key":"ref_22","first-page":"9","article-title":"3D-QSAR, ADMET, and Molecular Docking Studies for Designing New 1,3,5-Triazine Derivatives as Anticancer Agents","volume":"65","author":"Khaldan","year":"2022","journal-title":"Egypt. J. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Roncato, R., Angelini, J., Pani, A., Cecchin, E., Sartore-Bianchi, A., Siena, S., De Mattia, E., Scaglione, F., and Toffoli, G. (2020). CDK4\/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176350"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1158\/1535-7163.MCT-16-0300","article-title":"Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance","volume":"15","author":"Chen","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2202358","DOI":"10.1080\/14756366.2023.2202358","article-title":"Development of new TAK-285 derivatives as potent EGFR\/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines","volume":"38","author":"Son","year":"2023","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s43094-020-00084-4","article-title":"In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and druglikeness predictions","volume":"6","author":"Umar","year":"2020","journal-title":"Future J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1021\/jm0492002","article-title":"A Bioavailability Score","volume":"48","author":"Martin","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cmdc.200700139","article-title":"Lessons learnt from assembling screening libraries for drug discovery for neglected diseases","volume":"3","author":"Brenk","year":"2008","journal-title":"Chem. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.toxrep.2017.07.001","article-title":"Neuropharmacological profile and chemical analysis of fresh rhizome essential oil of Curcuma longa (turmeric) cultivated in Southwest Nigeria","volume":"17","author":"Oyemitan","year":"2017","journal-title":"Toxicol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155155","DOI":"10.1016\/j.phymed.2023.155155","article-title":"Role of polyphenols in the management of diabetic complications","volume":"122","author":"Raina","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1177\/10600280211073009","article-title":"Antiplatelet Use in Ischemic Stroke","volume":"56","author":"Kamarova","year":"2022","journal-title":"Ann. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/0975-7406.106563","article-title":"Synthesis and PASS-assisted in silico approach of some novel 2-substituted benzimidazole bearing a pyrimidine-2, 4, 6(trione) system as mucomembranous protector","volume":"5","author":"Mathew","year":"2013","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Eddin, L.B., Jha, N.K., Goyal, S.N., Agrawal, Y.O., Subramanya, S.B., Bastaki, S.M.A., and Ojha, S. (2022). Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of \u03b1-Bisabolol. Nutrients, 14.","DOI":"10.3390\/nu14071370"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bakheit, A.H., Attwa, M.W., Kadi, A.A., Ghabbour, H.A., and Alkahtani, H.M. (2023). Exploring the Chemical Reactivity, Molecular Docking, Molecular Dynamic Simulation and ADMET Properties of a Tetrahydrothienopyridine Derivative Using Computational Methods. Crystals, 13.","DOI":"10.3390\/cryst13071020"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132103","DOI":"10.1016\/j.jhazmat.2023.132103","article-title":"Examining the impact of nanoplastics and PFAS exposure on immune functions through inhibition of secretory immunoglobin A in human breast milk","volume":"459","author":"Enyoh","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5006\/1.3290328","article-title":"Corrosion Inhibitors Correlation between Electronic Structure and Efficiency","volume":"57","author":"Lukovits","year":"2011","journal-title":"Corrosion"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10698-022-09416-z","article-title":"Density functional theory, chemical reactivity, and the Fukui functions","volume":"24","author":"Pucci","year":"2022","journal-title":"Found. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1021\/cr040109f","article-title":"Electrophilicity index","volume":"106","author":"Chattaraj","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.59049\/2790-0231.1115","article-title":"Dereplication Study and Pharmacological Potentials of Phytochemical Constituents of Nigerian Propolis from Umudike","volume":"9","author":"Ugariogu","year":"2024","journal-title":"Palest. Med. Pharm. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1021\/acsfoodscitech.2c00217","article-title":"In Silico Screening of Active Compounds in Garri for the Inhibition of Key Enzymes Linked to Diabetes Mellitus","volume":"2","author":"Enyoh","year":"2022","journal-title":"ACS Food Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/bjc.2011.590","article-title":"Phase I first-in-human study of TAK-285, a novel investigational dual HER2\/EGFR inhibitor, in cancer patients","volume":"106","author":"Doi","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kumar, S., Saini, V., Maurya, I.K., Sindhu, J., Kumari, M., Kataria, R., and Kumar, V. (2018). Design, synthesis, DFT, docking studies and ADME prediction of some new coumarinyl linked pyrazolylthiazoles: Potential standalone or adjuvant antimicrobial agents. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196016"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/ja00364a005","article-title":"Absolute hardness: Companion parameter to absolute electronegativity","volume":"105","author":"Parr","year":"1983","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8440","DOI":"10.1073\/pnas.83.22.8440","article-title":"Absolute electronegativity and hardness correlated with molecular orbital theory","volume":"83","author":"Pearson","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:43:26Z","timestamp":1779893006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060834"],"URL":"https:\/\/doi.org\/10.3390\/ph19060834","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}