{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:53:34Z","timestamp":1793217214236,"version":"4.5.0"},"reference-count":21,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR24992814"],"award-info":[{"award-number":["BR24992814"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Bee products are rich sources of bioactive flavonoids with potential applications in nutraceutical and pharmaceutical research. However, differences in the physicochemical and pharmacokinetic properties of individual flavonoids may substantially influence their drug-likeness and bioavailability. This study aimed to characterize the pharmacokinetic, physicochemical, and drug-likeness profiles of four representative flavonoids commonly associated with bee products myricetin, galangin, kaempferol, and quercetin. Methods\n                    <ns3:italic>In silico<\/ns3:italic>\n                    pharmacokinetic and drug-likeness analyses were performed using the SwissADME web platform. The investigated compounds were evaluated in terms of physicochemical properties, lipophilicity, aqueous solubility, gastrointestinal absorption, blood-brain barrier (BBB) permeability, P-glycoprotein (P-gp) substrate status, and compliance with established drug-likeness rules, including Lipinski, Veber, Egan, and Muegge criteria. Results All four flavonoids exhibited favorable molecular properties and an identical predicted bioavailability score of 0.55. Galangin, kaempferol, and quercetin showed high predicted gastrointestinal absorption and fully complied with the Lipinski, Veber, Egan, and Muegge drug-likeness criteria. In contrast, myricetin exhibited comparatively lower predicted gastrointestinal absorption, which may be associated with its higher polarity, greater hydrogen-bonding capacity, and elevated topological polar surface area. None of the investigated flavonoids was predicted to penetrate the BBB or to act as a P-gp substrate. Variations in hydroxyl substitution were associated with marked differences in lipophilicity, aqueous solubility, membrane permeability, and overall pharmacokinetic behavior. Among the compounds evaluated, galangin displayed the most balanced physicochemical and medicinal chemistry profile, whereas kaempferol and quercetin also demonstrated favorable characteristics for oral drug development. Conclusions The findings indicate that flavonoids associated with Kazakhstan bee products possess distinct but generally favorable drug-likeness and predicted pharmacokinetic profiles. In particular, galangin emerged as the most balanced candidate among the compounds examined. Integrating\n                    <ns3:italic>in silico<\/ns3:italic>\n                    pharmacokinetic assessment with knowledge of bee-product composition may contribute to the scientific evaluation, quality standardization, and value-added utilization of Kazakhstan\u2019s apicultural resources, while providing a basis for further experimental investigation of their nutraceutical and pharmaceutical potential.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.188625.1","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:14:06Z","timestamp":1789967646000},"page":"1422","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Beekeeping Sector of Kazakhstan and Contributions to the Pharmaceutical Industry: Promising Flavonoids with the Pharmacokinetic Properties Via the Computational Evaluations"],"prefix":"10.12688","volume":"15","author":[{"given":"\u015eeyda","family":"Kaya","sequence":"first","affiliation":[{"name":"Department of Medical Services and Techniques, Medical Laboratory Techniques Program, Vocational School of Health Services Gaziantep Gaziantep Islam Science and Technology University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9056-6435","authenticated-orcid":false,"given":"Zeliha","family":"Selamoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medicine Faculty Ni\u011fde Ni\u011fde Omer Halisdemir University"},{"name":"Department of Biology, Faculty of Sciences Turkestan Khoja Akhmet Yassawi International Kazakh-Turkish University"},{"name":"Department of Biology, Faculty of Sciences Baku Western Caspian University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Durna Da\u015ftan","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science Sivas Sivas Cumhuriyet University"},{"name":"Beekeeping Development, Application and Research Center Sivas Sivas Cumhuriyet University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulkinzhon","family":"Gaipov","sequence":"additional","affiliation":[{"name":"Center for Sustainable Development and Scientific Research Turkistan Khoja Akhmet Yassawi International Kazakh-Turkish University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taner","family":"Da\u015ftan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science Sivas Sivas Cumhuriyet University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurdana","family":"Salybekova","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Turkestan Khoja Akhmet Yassawi International Kazakh-Turkish University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2719-2740","DOI":"10.1021\/jm901137j","article-title":"New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays.","volume":"53","author":"J Baell","year":"2010","journal-title":"J. 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Rep."}],"updated-by":[{"DOI":"10.12688\/f1000research.188625.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000}}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:19:33Z","timestamp":1791890373000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":21,"URL":"https:\/\/doi.org\/10.12688\/f1000research.188625.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.208184.r518703","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.208184.r518694","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.12688\/f1000research.188625.2","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.208184.r518694, Kamala Badalova, Azerbaijan Medical University, Baku, Baku, 10 Sep 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1#referee-response-518694","order":0,"name":"referee-response-518694","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Zeliha Selamoglu<\/b>; \n<i>Posted: 17 Sep 2026<\/i>; We sincerely thank the reviewer for their thoughtful and encouraging evaluation of our manuscript. We are pleased that the reviewer found the comparative structure\u2013property approach informative, and we agree that the identification of galangin as the most balanced candidate, alongside the reduced predicted bioavailability of myricetin, represents one of the more actionable findings of this study for future research prioritization. We also fully concur with the reviewer's note that experimental (\n<i>in vitro\/in vivo<\/i>) validation remains a necessary next step before any therapeutic or drug-development claims can be substantiated; we have been careful throughout the manuscript to frame our findings as computational predictions requiring further validation, and we appreciate the reviewer's reinforcement of this point. We are grateful for the reviewer's time and expertise in assessing this work.","URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1#referee-comment-17192","order":1,"name":"referee-comment-17192","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.208184.r518703, Ramin Ekhteiari Salmas, King's College London, London, England, 16 Sep 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1#referee-response-518703","order":2,"name":"referee-response-518703","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Zeliha Selamoglu<\/b>; \n<i>Posted: 17 Sep 2026<\/i>; We sincerely thank the reviewer for the positive and constructive evaluation of our manuscript, and for confirming that the study design, methodology, data availability, and conclusions meet an acceptable scientific standard. We have addressed each of the reviewer's five suggestions below, and believe these revisions have improved the clarity and completeness of the manuscript.  We thank the reviewer for this suggestion. We would like to clarify that the 2D chemical structures of all four flavonoids are already presented in Figure 2, alongside their corresponding SwissADME bioavailability radar plots, so that structural features and predicted physicochemical behavior can be visually compared side by side. We had intentionally kept Table 3 limited to textual identifiers (PubChem CID, IUPAC name, canonical SMILES) to avoid duplicating the same graphical content in two places within the manuscript. To address the reviewer's concern for ease of reference, we have added an explicit cross-reference in the Table 3 caption directing readers to Figure 2 for the corresponding 2D structures. Yes. Our results reveal a clear structure\u2013property relationship among the four flavonoids: increasing hydroxyl substitution (galangin &lt; kaempferol &lt; quercetin &lt; myricetin) is associated with a progressive increase in TPSA, hydrogen-bond donor\/acceptor count, and predicted aqueous solubility, alongside a progressive decrease in Consensus Log Po\/w, skin permeability, and predicted gastrointestinal absorption. We thank the reviewer for prompting us to make this relationship explicit, as it had previously been discussed only in a fragmented manner across separate paragraphs. A new synthesizing paragraph has been added to the Results section summarizing this structure\u2013property trend. We thank the reviewer for this suggestion. However, we would prefer to retain the IUPAC names and canonical SMILES strings within Table 3 in the main text, as these identifiers are essential for reproducibility and independent verification of the compounds studied, and their removal to the Supporting Information could reduce accessibility for readers directly comparing structural and pharmacokinetic data. As noted in our response to Comment 1, we have added a cross-reference in the Table 3 caption directing readers to Figure 2 for the corresponding 2D structures, which we believe addresses the reviewer's core concern regarding visual clarity without requiring readers to consult supplementary material for basic chemical identifiers. We thank the reviewer for highlighting this gap. A short paragraph has been added to the Materials and Methods section summarizing the computational basis of the key predictions used: TPSA is calculated using the fragment-based topological method; the Consensus Log Po\/w is the arithmetic mean of five independent prediction models (XLOGP3, WLOGP, MLOGP, SILICOS-IT, and iLOGP); the BOILED-Egg model classifies gastrointestinal absorption and blood-brain barrier permeation using WLOGP and TPSA within a Monte-Carlo-optimized probability ellipse; and the bioavailability score follows the rule-based classification originally described by (Martin et al. 2005). Yes. As a direct follow-up to this\n<i> in silico<\/i> screening, we plan to pursue experimental validation of the predicted pharmacokinetic differences among the four flavonoids, particularly the comparatively lower gastrointestinal absorption of myricetin, using \n<i>in vitro<\/i> permeability assays. In parallel, we intend to characterize the biological activity of these compounds as they occur naturally in Kazakhstan-sourced bee products (honey, pollen, and propolis), including antioxidant and anti-inflammatory bioassays, to bridge the present computational findings with experimentally verifiable outcomes. A statement to this effect has been added to the Conclusion.  We are grateful to the reviewer for their time, expertise, and valuable suggestions, which have helped us improve the manuscript. We hope that the revised version now meets the requirements for acceptance.","URL":"https:\/\/f1000research.com\/articles\/15-1422\/v1#referee-comment-17191","order":3,"name":"referee-comment-17191","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study was supported by grant BR24992814 from the Scientific Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan, awarded for the development of innovative technologies and scientific infrastructure for the sustainable development of the South Kazakhstan region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}