{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:03:54Z","timestamp":1790946234226,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (\u03b1-ketoamide inhibitor (KI), IC50 = 66.72 \u00b5g\/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 \u00b5g\/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/molecules26216559","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:22:24Z","timestamp":1635805344000},"page":"6559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-6073","authenticated-orcid":false,"given":"Ahmed A.","family":"Al-Karmalawy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai M.","family":"Farid","sequence":"additional","affiliation":[{"name":"Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-5714","authenticated-orcid":false,"given":"Ahmed","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia Y.","family":"Ragheb","sequence":"additional","affiliation":[{"name":"Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"H. Mahmoud","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-9398","authenticated-orcid":false,"given":"Mahmoud","family":"Shehata","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"},{"name":"Institute of Medical Virology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura M. Abo","family":"Shama","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"GabAllah","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-0495","authenticated-orcid":false,"given":"Gomaa","family":"Mostafa-Hedeab","sequence":"additional","affiliation":[{"name":"Pharmacology Department & Health Research Unit, Medical College, Jouf University, Skaka 11564, Saudi Arabia"},{"name":"Pharmacology Department, Medical College, Beni-Suef University, Beni-Suef 62521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3176-1470","authenticated-orcid":false,"given":"Mona M.","family":"Marzouk","sequence":"additional","affiliation":[{"name":"Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","unstructured":"Kamps, B.S., and Christia, H. (2021). COVID Reference, Steinhauser Verlag. Available online: https:\/\/amedeo.com\/CovidReference06.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29267","DOI":"10.1039\/D1RA05268C","article-title":"Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights","volume":"11","author":"Elebeedy","year":"2021","journal-title":"RSC Adv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kandeil, A. (2021). Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies. Vaccines, 9.","DOI":"10.3390\/vaccines9030214"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shehata, M.M. (2021). In Silico and In Vivo Evaluation of SARS-CoV-2 Predicted Epitopes-Based Candidate Vaccine. Molecules, 26.","DOI":"10.3390\/molecules26206182"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"El Gizawy, H.A. (2021). Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies. Molecules, 26.","DOI":"10.3390\/molecules26195844"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31339","DOI":"10.1039\/D1RA05817G","article-title":"Investigating the structure\u2013activity relationship of marine natural polyketides as promising SARS-CoV-2 main protease inhibitors","volume":"11","year":"2021","journal-title":"RSC Adv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102845","DOI":"10.1016\/j.jddst.2021.102845","article-title":"Delineating a potent antiviral activity of Cuphea ignea extract loaded nano-formulation against SARS-CoV-2: In silico and in vitro studies","volume":"66","author":"Mahmoud","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Roviello, V., and Roviello, G.N. (2021). Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant volatile organic compounds. Environ. Chem. Lett., 1\u201311.","DOI":"10.1007\/s10311-021-01309-5"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Vicidomini, C., Roviello, V., and Roviello, G.N. (2021). In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro. Symmetry, 13.","DOI":"10.3390\/sym13061041"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104362","DOI":"10.1016\/j.compbiomed.2021.104362","article-title":"Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants","volume":"133","author":"Muhammad","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ibrahim, M.A. (2021). Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition. Mar. Drugs, 19.","DOI":"10.3390\/md19070391"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153476","DOI":"10.1016\/j.phymed.2021.153476","article-title":"Toxicity as prime selection criterion among SARS-active herbal medications","volume":"85","author":"Oesch","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vicidomini, C., Roviello, V., and Roviello, G.N. (2021). Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility. Molecules, 26.","DOI":"10.3390\/molecules26071880"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.3390\/v4102197","article-title":"Hepatitis C virus and natural compounds: A new antiviral approach?","volume":"4","author":"Calland","year":"2012","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/np300727f","article-title":"Antiviral phenolic compounds from Arundina gramnifolia","volume":"76","author":"Hu","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shoala, T. (2021). Nanobiotechnological Approaches to Enhance Potato Resistance against Potato Leafroll Virus (PLRV) Using Glycyrrhizic Acid Ammonium Salt and Salicylic Acid Nanoparticles. Horticulturae, 7.","DOI":"10.3390\/horticulturae7100402"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ngwa, W. (2020). Potential of flavonoid-inspired phytomedicines against COVID-19. Molecules, 25.","DOI":"10.3390\/molecules25112707"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/14756366.2019.1690480","article-title":"Inhibition of SARS-CoV 3CL protease by flavonoids","volume":"35","author":"Jo","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Abo Elmaaty, A. (2021). Computational Insights on the Potential of Some NSAIDs for Treating COVID-19: Priority Set and Lead Optimization. Molecules, 26.","DOI":"10.3390\/molecules26123772"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e07962","DOI":"10.1016\/j.heliyon.2021.e07962","article-title":"Telaprevir is a potential drug for repurposing against SARS-CoV-2: Computational and in vitro studies","volume":"7","author":"Mahmoud","year":"2021","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al-Karmalawy, A.A., and Eissa, I.H. (2021). Molecular docking and dynamics simulations reveal the potential of anti-HCV drugs to inhibit COVID-19 main protease. Pharm. Sci., 27.","DOI":"10.34172\/PS.2021.3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100604","DOI":"10.1016\/j.imu.2021.100604","article-title":"The journey of antimalarial drugs against SARS-CoV-2: Review article","volume":"24","author":"Sarhan","year":"2021","journal-title":"Inform. Med. Unlocked"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zaki, A.A. (2021). Calendulaglycoside A Showing Potential Activity Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and SAR Studies. J. Tradit. Complement. Med.","DOI":"10.1016\/j.jtcme.2021.05.001"},{"key":"ref_24","first-page":"1","article-title":"In a search for potential drug candidates for combating COVID-19: Computational study revealed salvianolic acid B as a potential therapeutic targeting 3CLpro and spike proteins","volume":"30","author":"Elmaaty","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Soltane, R. (2021). Strong Inhibitory Activity and Action Modes of Synthetic Maslinic Acid Derivative on Highly Pathogenic Coronaviruses: COVID-19 Drug Candidate. Pathogens, 10.","DOI":"10.3390\/pathogens10050623"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10027","DOI":"10.1039\/D0RA10674G","article-title":"Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: Theoretical study","volume":"11","author":"Elmaaty","year":"2021","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Soltan, M.A. (2021). In Silico Prediction of a Multitope Vaccine against Moraxella catarrhalis: Reverse Vaccinology and Immunoinformatics. Vaccines, 9.","DOI":"10.3390\/vaccines9060669"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Soltan, M.A. (2021). Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179330"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Brogi, S. (2019). Computational approaches for drug discovery. Molecules, 24.","DOI":"10.3390\/molecules24173061"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13990","DOI":"10.1039\/D0NJ02844D","article-title":"Molecular modelling of mebendazole polymorphs as a potential colchicine binding site inhibitor","volume":"44","author":"Khattab","year":"2020","journal-title":"New J. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3389\/fchem.2021.628398","article-title":"Revisiting Activity of Some Nocodazole Analogues as a Potential Anticancer Drugs Using Molecular Docking and DFT Calculations","volume":"9","author":"Khattab","year":"2021","journal-title":"Front. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e08148","DOI":"10.1016\/j.heliyon.2021.e08148","article-title":"In vitro and in silico characterization of alkaline serine protease from Bacillus subtilis D9 recovered from Saudi Arabia","volume":"7","author":"Mahmoud","year":"2021","journal-title":"Heliyon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s11030-020-10150-x","article-title":"Computational guided identification of a citrus flavonoid as potential inhibitor of SARS-CoV-2 main protease","volume":"25","author":"Gogoi","year":"2021","journal-title":"Mol. Divers."},{"key":"ref_34","first-page":"2150013","article-title":"Virtual screening of citrus flavonoid tangeretin: A promising pharmacological tool for the treatment and prevention of Zika fever and COVID-19","volume":"20","year":"2021","journal-title":"J. Comput. Biophys. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Omar, S., Bouziane, I., Bouslama, Z., and Djemel, A. (2020). In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2. ChemRxiv.","DOI":"10.26434\/chemrxiv.12181404.v1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kandeil, A. (2021). Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2. Pathogens, 10.","DOI":"10.3390\/pathogens10060758"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e05641","DOI":"10.1016\/j.heliyon.2020.e05641","article-title":"Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease","volume":"6","author":"Alnajjar","year":"2020","journal-title":"Heliyon"},{"key":"ref_38","first-page":"227","article-title":"Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor","volume":"9","year":"2021","journal-title":"Front. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16752","DOI":"10.1039\/D0NJ03611K","article-title":"Molecular docking reveals the potential of Cleome amblyocarpa isolated compounds to inhibit COVID-19 virus main protease","volume":"44","author":"Zaki","year":"2020","journal-title":"New J. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.bbrc.2017.08.106","article-title":"Pectolinarigenin, an aglycone of pectolinarin, has more potent inhibitory activities on melanogenesis than pectolinarin","volume":"493","author":"Lee","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s12272-010-0302-6","article-title":"Antidiabetic effect of flavones from Cirsium japonicum DC in diabetic rats","volume":"33","author":"Liao","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1248\/bpb.31.760","article-title":"Pectolinarin and pectolinarigenin of Cirsium setidens prevent the hepatic injury in rats caused by D-galactosamine via an antioxidant mechanism","volume":"31","author":"Yoo","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1016\/j.bmcl.2005.07.029","article-title":"Potential antitumor agents: Flavones and their derivatives from Linaria reflexa Desf","volume":"15","author":"Tundis","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.cbi.2016.07.016","article-title":"Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species","volume":"256","author":"Cabrera","year":"2016","journal-title":"Chem.-Biol. Interact."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0031-9422(00)97104-8","article-title":"Highly oxygenated bioactive flavones from Tamarix","volume":"36","author":"Parmar","year":"1994","journal-title":"Phytochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0022-2860(71)87109-0","article-title":"The systematic identification of flavonoids: By T.J. Mabry, K.R. Markham and M.B. Thomas, Springer-Verlag, Berlin-Heidelberg-New York, 1970, pp. xii + 354, price DM.98.00, \u00a311.75, $27.00","volume":"10","author":"Harborne","year":"1971","journal-title":"J. Mol. Struct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S0960-894X(03)00088-X","article-title":"Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica","volume":"13","author":"Yoshikawa","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101431","DOI":"10.1016\/j.bcab.2019.101431","article-title":"Isoscutellarein 8,4\u2032-dimethyl ether glycosides as cytotoxic agents and chemotaxonomic markers in Kickxia aegyptiaca","volume":"22","author":"Farid","year":"2019","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.ijbiomac.2020.07.305","article-title":"Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation","volume":"164","author":"Huang","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s10600-006-0228-x","article-title":"Phenolic compounds from Centaurea africana","volume":"42","author":"Seghiri","year":"2006","journal-title":"Chem. Nat. Compd."},{"key":"ref_51","unstructured":"Chemical Computing Group Inc. (2021). Molecular Operating Environment (MOE), 2016, Chemical Computing Group Inc."},{"key":"ref_52","first-page":"185","article-title":"Design, synthesis, molecular docking and biological evaluation of some novel quinazoline-4 (3H)-one derivatives as anti-inflammatory agents","volume":"46","author":"Ibrahim","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17374","DOI":"10.1039\/D0NJ04088F","article-title":"Tanshinone IIA synergistically enhances the antitumor activity of doxorubicin by interfering with the PI3K\/AKT\/mTOR pathway and inhibition of topoisomerase II: In vitro and molecular docking studies","volume":"44","author":"Ghanem","year":"2020","journal-title":"New J. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"16557","DOI":"10.1039\/D1NJ02710G","article-title":"Design and synthesis of new 4-(2-nitrophenoxy)benzamide derivatives as potential antiviral agents: Molecular modeling and in vitro antiviral screening","volume":"45","author":"Abdallah","year":"2021","journal-title":"New J. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"116266","DOI":"10.1016\/j.bmc.2021.116266","article-title":"From triazolophthalazines to triazoloquinazolines: A bioisosterism-guided approach toward the identification of novel PCAF inhibitors with potential anticancer activity","volume":"42","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"443","DOI":"10.34172\/jhp.2021.52","article-title":"Two new flavonoids and anticancer activity of Hymenosporum flavum: In vitro and molecular docking studies","volume":"10","author":"Taher","year":"2021","journal-title":"J. Herbmed Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.sajb.2021.02.007","article-title":"Bioassay-guided isolation of a new cytotoxic ceramide from Cyperus rotundus L.","volume":"139","author":"Samra","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_59","unstructured":"Al-Karmalawy, A.A., and Elshal, M.F. (2021). Concanavalin-A shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: In vitro and molecular docking studies. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e2100258","DOI":"10.1002\/ardp.202100258","article-title":"Pharmacophore-linked pyrazolo [3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies","volume":"10","author":"Gaber","year":"2021","journal-title":"Arch. Pharm."},{"key":"ref_61","first-page":"101","article-title":"Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl-3-substituted-quinazolin-4 (3H)-ones","volume":"53","author":"Ibrahim","year":"2015","journal-title":"Bull. Fac. Pharm. Cairo Univ."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1021\/acsptsci.0c00144","article-title":"Empagliflozin and Doxorubicin Synergistically Inhibit the Survival of Triple-Negative Breast Cancer Cells via Interfering with the mTOR Pathway and Inhibition of Calmodulin: In Vitro and Molecular Docking Studies","volume":"3","author":"Eliaa","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"725135","DOI":"10.3389\/fchem.2021.725135","article-title":"Design and Synthesis of New Quinoxaline Derivatives as Potential Histone Deacetylase Inhibitors Targeting Hepatocellular Carcinoma: In Silico, In Vitro, and SAR Studies","volume":"9","year":"2021","journal-title":"Front. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13986","DOI":"10.1039\/D1NJ02838C","article-title":"The antimicrobial potential and pharmacokinetic profiles of novel quinoline-based scaffolds: Synthesis and in silico mechanistic studies as dual DNA gyrase and DHFR inhibitors","volume":"45","year":"2021","journal-title":"New J. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.sajb.2021.08.006","article-title":"Isolation of cytotoxic active compounds from Reichardia tingitana with investigation of apoptosis mechanistic induction: In silico, in vitro, and SAR studies","volume":"144","author":"Zaki","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4155\/fmc-2020-0273","article-title":"Computational repurposing of benzimidazole anthelmintic drugs as potential colchicine binding site inhibitors","volume":"13","author":"Khattab","year":"2021","journal-title":"Future Med. Chem."},{"key":"ref_67","first-page":"e2000237","article-title":"Design and discovery of new 1,2,4-triazolo[4,3-c] quinazolines as potential DNA intercalators and topoisomerase II inhibitors","volume":"3","author":"Alesawy","year":"2020","journal-title":"Arch. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"087379","DOI":"10.1101\/pdb.prot087379","article-title":"Crystal violet assay for determining viability of cultured cells","volume":"2016","author":"Feoktistova","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mostafa, A. (2020). FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120443"},{"key":"ref_70","first-page":"22","article-title":"Coding-complete genome sequences of two SARS-CoV-2 isolates from Egypt","volume":"9","year":"2020","journal-title":"Microbiol. Resour. Announc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:04Z","timestamp":1760167384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,29]]},"references-count":70,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216559"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216559","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,29]]}}}