{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T07:23:44Z","timestamp":1782026624973,"version":"3.54.5"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-36890-8","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:25:02Z","timestamp":1769520302000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and anticancer evaluation of novel thioimidazole derivatives bearing a trimethoxyphenyl moiety"],"prefix":"10.1038","volume":"16","author":[{"given":"Natalia","family":"Maciejewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birut\u0117","family":"Grybait\u0117","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimieras","family":"Anusevi\u010dius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vytautas","family":"Mickevi\u010dius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"36890_CR1","doi-asserted-by":"publisher","first-page":"838","DOI":"10.3390\/molecules28020838","volume":"28","author":"HV Tolomeu","year":"2023","unstructured":"Tolomeu, H. V. & Fraga, C. A. M. Imidazole synthesis, functionalization and physicochemical properties of a privileged structure in medicinal chemistry. Molecules 28, 838 (2023).","journal-title":"Molecules"},{"key":"36890_CR2","doi-asserted-by":"publisher","unstructured":"Verma, A., Joshi, S. & Singh, D. Imidazole: having versatile biological activities. J. Chem. 2013 (329412). https:\/\/doi.org\/10.3390\/molecules28020838 (2013).","DOI":"10.3390\/molecules28020838"},{"key":"36890_CR3","doi-asserted-by":"publisher","first-page":"121320","DOI":"10.1016\/j.molliq.2023.121320","volume":"375","author":"X Zhang","year":"2023","unstructured":"Zhang, X. et al. Insight into the stabilization mechanism of imidazole-based ionic liquids at the interface of the carbon nanotubes: A computational study. J. Mol. Liq. 375, 121320. https:\/\/doi.org\/10.1016\/j.molliq.2023.121320 (2023).","journal-title":"J. Mol. Liq."},{"key":"36890_CR4","doi-asserted-by":"publisher","unstructured":"Gujjarappa, R. et al. Overview on biological activities of imidazole derivatives. In Materials Horizons: from Nature To Nanomaterials, Vol. 1, no. 6, 135\u2013227. (Springer, 2022). https:\/\/doi.org\/10.1007\/978-981-16-8399-2_6.","DOI":"10.1007\/978-981-16-8399-2_6"},{"key":"36890_CR5","doi-asserted-by":"publisher","first-page":"132726","DOI":"10.1016\/j.molstruc.2022.132726","volume":"1259","author":"ARE Mahdy","year":"2022","unstructured":"Mahdy, A. R. E. et al. Synthesis, characterization, and biological activity of Co(II) and Zn(II) complexes of imidazoles-based azo-functionalized schiff bases. J. Mol. Struct. 1259, 132726. https:\/\/doi.org\/10.1016\/j.molstruc.2022.132726 (2022).","journal-title":"J. Mol. Struct."},{"key":"36890_CR6","doi-asserted-by":"publisher","unstructured":"Romero, D. H., Heredia, V. E. T., Garc\u00eda-Barradas, O., L\u00f3pez, Ma, E. M. & Pav\u00f3n, E. S. Synthesis of imidazole derivatives and their biological activities. JCB 2 https:\/\/doi.org\/10.15640\/JCB.V2N2A3 (2014).","DOI":"10.15640\/JCB.V2N2A3"},{"key":"36890_CR7","doi-asserted-by":"publisher","unstructured":"Muheyuddeen, G. et al. Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular Docking insights. Sci. Rep. 14 (23121). https:\/\/doi.org\/10.1038\/s41598-024-72399-8 (2024).","DOI":"10.1038\/s41598-024-72399-8"},{"key":"36890_CR8","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1007\/s00706-018-2167-1","volume":"15","author":"A Puratchikody","year":"2007","unstructured":"Puratchikody, A. & Doble, M. Antinociceptive and antiinflammatory activities and QSAR studies on 2-substituted-4,5-diphenyl-1H-imidazoles. Bioorg. Med. Chem. 15, 1083\u20131090. https:\/\/doi.org\/10.1007\/s00706-018-2167-1 (2007).","journal-title":"Bioorg. Med. Chem."},{"key":"36890_CR9","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1007\/s00706-020-02636-6","volume":"149","author":"R Ghorbani-Vaghei","year":"2018","unstructured":"Ghorbani-Vaghei, R., Izadkhah, V., Mahmoodi, J., Karamian, R. & Ahmadi Khoei, M. The synthesis of imidazoles and evaluation of their antioxidant and antifungal activities. Monatshefte Chem. 149, 1447\u20131452. https:\/\/doi.org\/10.1007\/s00706-020-02636-6 (2018).","journal-title":"Monatshefte Chem."},{"key":"36890_CR10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.21448\/ijsm.714310","volume":"7","author":"BK Yard\u0131mc\u0131","year":"2020","unstructured":"Yard\u0131mc\u0131, B. K. Imidazole antifungals: A review of their action mechanisms on cancerous cells. Int. J. Second. Metabo. 7, 139\u2013159. https:\/\/doi.org\/10.21448\/ijsm.714310 (2020).","journal-title":"Int. J. Secondary Metabolite"},{"key":"36890_CR11","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.bmcl.2010.12.029","volume":"21","author":"V Malhotra","year":"2011","unstructured":"Malhotra, V., Pathak, S. R., Nath, R., Mukherjee, D. & Shanker, K. Substituted imidazole derivatives as novel cardiovascular agents. Bioorg. Med. Chem. Lett. 21, 936\u2013939. https:\/\/doi.org\/10.1016\/j.bmcl.2010.12.029 (2011).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"36890_CR12","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1016\/j.bmc.2010.04.038","volume":"18","author":"G Navarrete-V\u00e1zquez","year":"2010","unstructured":"Navarrete-V\u00e1zquez, G. et al. Synthesis, vasorelaxant activity and antihypertensive effect of Benzo[d]imidazole derivatives. Bioorg. Med. Chem. 18, 3985\u20133991. https:\/\/doi.org\/10.1016\/j.bmc.2010.04.038 (2010).","journal-title":"Bioorg. Med. Chem."},{"key":"36890_CR13","doi-asserted-by":"publisher","first-page":"7245","DOI":"10.26355\/eurrev_202210_29917","volume":"26","author":"A Unnisa","year":"2022","unstructured":"Unnisa, A. et al. Design, in Silico study, synthesis and in vitro evaluation of some N5-(1H-pyrazol-3-yl)-3H-benzo[d]imidazole-2,5-diamine derivatives as potential pancreatic lipase inhibitors for anti-obesity activity. Eur. Rev. Med. Pharmacol. Sci. 26, 7245\u20137255. https:\/\/doi.org\/10.26355\/eurrev_202210_29917 (2022).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"36890_CR14","doi-asserted-by":"publisher","unstructured":"Chopra, P. N. & Sahu, J. K. Biological significance of Imidazole-based analogues in new drug development. Current Drug Discov. Technol. 17, 574\u2013584 https:\/\/doi.org\/10.2174\/1570163816666190320123340 (2020).","DOI":"10.2174\/1570163816666190320123340"},{"key":"36890_CR15","doi-asserted-by":"publisher","first-page":"2903","DOI":"10.1515\/psr-2021-0041","volume":"8","author":"N Kumar","year":"2023","unstructured":"Kumar, N. & Goel, N. Recent development of imidazole derivatives as potential anticancer agents. Phys. Sci. Rev. 8, 2903\u20132941. https:\/\/doi.org\/10.1515\/psr-2021-0041 (2023).","journal-title":"Phys. Sci. Reviews"},{"key":"36890_CR16","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.3390\/molecules30102245","volume":"30","author":"Z Murtazaeva","year":"2025","unstructured":"Murtazaeva, Z. et al. Imidazole hybrids: A privileged class of heterocycles in medicinal chemistry with new insights into anticancer activity. Molecules 30, 2245. https:\/\/doi.org\/10.3390\/molecules30102245 (2025).","journal-title":"Molecules"},{"key":"36890_CR17","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1016\/j.ejmech.2008.05.002","volume":"44","author":"D Sharma","year":"2009","unstructured":"Sharma, D. et al. Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives. Eur. J. Med. Chem. 44, 2347\u20132353. https:\/\/doi.org\/10.1016\/j.ejmech.2008.05.002 (2009).","journal-title":"Eur. J. Med. Chem."},{"key":"36890_CR18","doi-asserted-by":"publisher","unstructured":"Teli, P., Sahiba, N., Sethiya, A., Soni, J. & Agarwal, S. Imidazole derivatives: impact and prospects in antiviral drug discovery. Imidazole-Based Drug Discov. 167\u2013193. https:\/\/doi.org\/10.1016\/B978-0-323-85479-5.00001-0 (2022).","DOI":"10.1016\/B978-0-323-85479-5.00001-0"},{"key":"36890_CR19","doi-asserted-by":"publisher","first-page":"e0007021","DOI":"10.1371\/journal.pntd.0007021","volume":"12","author":"MG Blanco","year":"2018","unstructured":"Blanco, M. G. et al. Diisopropylphenyl imidazole (DII): A new compound that exerts anthelmintic activity through novel molecular mechanisms. PLoS Negl. Trop. Dis. 12, e0007021. https:\/\/doi.org\/10.1371\/journal.pntd.0007021 (2018).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"36890_CR20","unstructured":"Bhatnagar, A., Sharma, P. K. & Kumar, N. A review on \u2018imidazoles\u2019: their chemistry and pharmacological potentials. Int. J. PharmTech Res. 3, 268\u2013282 (2011)."},{"key":"36890_CR21","doi-asserted-by":"publisher","first-page":"3350","DOI":"10.1016\/j.ejmech.2009.02.013","volume":"44","author":"J Pandey","year":"2009","unstructured":"Pandey, J. et al. Synthesis and antitubercular screening of imidazole derivatives. Eur. J. Med. Chem. 44, 3350\u20133355. https:\/\/doi.org\/10.1016\/j.ejmech.2009.02.013 (2009).","journal-title":"Eur. J. Med. Chem."},{"key":"36890_CR22","doi-asserted-by":"publisher","first-page":"643","DOI":"10.2174\/1389557520666201102094401","volume":"21","author":"D Parwani","year":"2021","unstructured":"Parwani, D. et al. Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives. Mini-Rev. Med. Chem. 21, 643\u2013657. https:\/\/doi.org\/10.2174\/1389557520666201102094401 (2021).","journal-title":"Mini-Reviews Med. Chem."},{"key":"36890_CR23","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.2174\/1381612828666220512095559","volume":"28","author":"LL de L\u00f3cio","year":"2022","unstructured":"de L\u00f3cio, L. L. et al. Application of heterocycles as an alternative for the discovery of new Anti-ulcer compounds: A mini-review. Curr. Pharm. Design. 28, 1373\u20131388. https:\/\/doi.org\/10.2174\/1381612828666220512095559 (2022).","journal-title":"Curr. Pharm. Design"},{"key":"36890_CR24","doi-asserted-by":"publisher","first-page":"314","DOI":"10.4103\/0974-8520.105260","volume":"33","author":"JS Shah","year":"2012","unstructured":"Shah, J. S. & Patel, J. R. Anti-ulcer activity of lucer against experimentally induced gastric ulcers in rats. Ayu 33, 314\u2013316. https:\/\/doi.org\/10.4103\/0974-8520.105260 (2012).","journal-title":"Ayu"},{"key":"36890_CR25","doi-asserted-by":"publisher","first-page":"152","DOI":"10.13005\/ojc\/400119","volume":"40","author":"D Singh","year":"2024","unstructured":"Singh, D., Kharb, R. & Sharma, S. K. Schiff\u2019s base imidazole derivatives synthesis and evaluation for their Anti-Inflammatory activity. Orient. J. Chem. 40, 152\u2013164. https:\/\/doi.org\/10.13005\/ojc\/400119 (2024).","journal-title":"Orient. J. Chem."},{"key":"36890_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134384","author":"G. A. Krishna","year":"2023","unstructured":"Krishna, G. A. et al. Transition metal complexes of imidazole derived schiff bases: Antioxidant\/anti inflammatory\/antimicrobial\/enzyme inhibition and cytotoxicity properties. J. Mol. Struct. https:\/\/doi.org\/10.1016\/j.molstruc.2022.134384 (2023).","journal-title":"J. Mol. Struct."},{"key":"36890_CR27","doi-asserted-by":"publisher","unstructured":"Goel, K. K. et al. Imidazoles as serotonin receptor modulators for treatment of depression: Structural insights and structure\u2013activity relationship studies. Pharmaceutics 15, 2208 : (2023). https:\/\/doi.org\/10.3390\/pharmaceutics15092208","DOI":"10.3390\/pharmaceutics15092208"},{"key":"36890_CR28","doi-asserted-by":"publisher","unstructured":"Abramets, I. I., Zayka, T. O., Evdokimov, D. V. & Kuznetsov, Y. V. ir Y. V. Sidorova. Researches of the imidazole and indole derivatives cerebroprotective activity and its impact on effects of antidepressants. \u0424\u0430\u0440\u043c\u0430\u043a\u043e\u043a\u0438\u043d\u0435\u0442\u0438\u043a\u0430 \u0438 \u0444\u0430\u0440\u043c\u0430\u043a\u043e\u0434\u0438\u043d\u0430\u043c\u0438\u043a\u0430 3, 18\u201324. https:\/\/doi.org\/10.37489\/2587-7836-2020-1-18-24 (2020).","DOI":"10.37489\/2587-7836-2020-1-18-24"},{"key":"36890_CR29","doi-asserted-by":"publisher","first-page":"100796","DOI":"10.1016\/j.rechem.2023.100796","volume":"5","author":"A Sadula","year":"2023","unstructured":"Sadula, A. & Gaddhe, L. Synthesis, computational studies and biological evaluation of novel Acenaphthoquinone-imidazole derivatives as dual inhibitors of HSP90 and Topo II in cancer therapy. Results Chem. 5, 100796. https:\/\/doi.org\/10.1016\/j.rechem.2023.100796 (2023).","journal-title":"Results Chem."},{"key":"36890_CR30","doi-asserted-by":"publisher","first-page":"102182","DOI":"10.1016\/j.rechem.2025.102182","volume":"15","author":"HT Hamad","year":"2025","unstructured":"Hamad, H. T. The anti-cancer effectiveness of some heterocyclic compounds containing sulfur atom. Results Chem. 15, 102182. https:\/\/doi.org\/10.1016\/j.rechem.2025.102182 (2025).","journal-title":"Results Chem."},{"key":"36890_CR31","doi-asserted-by":"publisher","unstructured":"Vainauskas, V. et al. Synthesis and characterization of Sulfonamide-Imidazole hybrids with in vitro antiproliferative activity against Anthracycline-Sensitive and resistant H69 small cell lung cancer cells. ChemMedChem 20 (e202500260). https:\/\/doi.org\/10.1002\/cmdc.202500260 (2025).","DOI":"10.1002\/cmdc.202500260"},{"key":"36890_CR32","doi-asserted-by":"publisher","first-page":"935","DOI":"10.3390\/microorganisms11040935","volume":"11","author":"B Balandis","year":"2023","unstructured":"Balandis, B. et al. Synthesis of novel Benzenesulfonamide-Bearing functionalized imidazole derivatives as novel candidates targeting Multidrug-Resistant Mycobacterium abscessus complex. Microorganisms 11, 935. https:\/\/doi.org\/10.3390\/microorganisms11040935 (2023).","journal-title":"Microorganisms"},{"key":"36890_CR33","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1007\/s11095-021-03093-x","volume":"38","author":"S Han","year":"2021","unstructured":"Han, S., Mei, L., Quach, T., Porter, C. & Trevaskis, N. Lipophilic conjugates of drugs: A tool to improve drug Pharmacokinetic and therapeutic profiles. Pharmacol. Res. 38, 1497\u20131518. https:\/\/doi.org\/10.1007\/s11095-021-03093-x (2021).","journal-title":"Pharmacol. Res."},{"key":"36890_CR34","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3390\/pharmaceutics17101340","volume":"17","author":"J Marinkovi\u0107","year":"2025","unstructured":"Marinkovi\u0107, J. et al. Silver(I) complexes bearing S-Alkyl Thiosalicylic acid derivatives: DNA\/BSA binding and antitumor activity in vitro and in vivo. Pharmaceutics 17, 1340. https:\/\/doi.org\/10.3390\/pharmaceutics17101340 (2025).","journal-title":"Pharmaceutics"},{"key":"36890_CR35","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1021\/jm201548z","volume":"55","author":"Y Yang","year":"2012","unstructured":"Yang, Y., Engkvist, O., Llin\u00e0s, A. & Chen, H. Beyond size, ionization state, and lipophilicity: influence of molecular topology on absorption, distribution, metabolism, excretion, and toxicity for druglike compounds. J. Med. Chem. 55, 3667\u20133677. https:\/\/doi.org\/10.1021\/jm201548z (2012).","journal-title":"J. Med. Chem."},{"key":"36890_CR36","doi-asserted-by":"publisher","first-page":"7006","DOI":"10.1021\/om400585b","volume":"32","author":"V Karthik","year":"2013","unstructured":"Karthik, V., Bhat, I. A. & Anantharaman, G. Backbone thio-functionalized Imidazol-2-ylidene\u2013Metal complexes: Synthesis, structure, electronic properties, and catalytic activity. Organometallics 32, 7006\u20137013. https:\/\/doi.org\/10.1021\/om400585b (2013).","journal-title":"Organometallics"},{"key":"36890_CR37","doi-asserted-by":"publisher","first-page":"6764","DOI":"10.1016\/j.bmcl.2013.10.024","volume":"23","author":"L Yurtta\u015f","year":"2013","unstructured":"Yurtta\u015f, L., Duran, M., Demirayak, \u015e., Gen\u00e7er, H. K. & Tunal\u0131, Y. Synthesis and initial biological evaluation of substituted 1-phenylamino-2-thio-4,5-dimethyl-1H-imidazole derivatives. Bioorg. Med. Chem. Lett. 23, 6764\u20136768. https:\/\/doi.org\/10.1016\/j.bmcl.2013.10.024 (2013).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"36890_CR38","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1021\/acs.oprd.0c00234","volume":"24","author":"VM Joshi","year":"2020","unstructured":"Joshi, V. M. et al. Practical and efficient synthesis of 2-Thio-imidazole Derivative\u2014ZY12201: A potent TGR5 agonist. Org. Process Res. Dev. 24, 1508\u20131514. https:\/\/doi.org\/10.1021\/acs.oprd.0c00234 (2020).","journal-title":"Org. Process Res. Dev."},{"key":"36890_CR39","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1007\/s11094-023-03007-8","volume":"57","author":"A Karakaya","year":"2023","unstructured":"Karakaya, A., \u00c7evik, U. A., Er\u00e7etin, T., \u00d6zkay, Y. & Kaplanc\u0131kl\u0131, Z. A. Synthesis of Imidazole-Thiazole derivatives as acetylcholinesterase and butyrylcholinesterase inhibitory activities. Pharm. Chem. J. 57, 1439\u20131443 (2023).","journal-title":"Pharm. Chem. J."},{"key":"36890_CR40","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1016\/j.bmcl.2010.03.068","volume":"20","author":"JHM Lange","year":"2010","unstructured":"Lange, J. H. M. et al. Probing the cannabinoid CB1\/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern. Bioorg. Med. Chem. Lett. 20, 2770\u20132775. https:\/\/doi.org\/10.1016\/j.bmcl.2010.03.068 (2010).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"36890_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.202200259","author":"J Yang","year":"2022","unstructured":"Yang, J., Zeng, T., Yan, K., Qin, Z. & Wen, J. Direct synthesis of alkylthioimidazoles: One-pot three\u2010component cross\u2010coupling mediated by paired electrolysis. Adv. Synth. Catal. https:\/\/doi.org\/10.1002\/adsc.202200259 (2022).","journal-title":"Adv. Synth. Catal."},{"key":"36890_CR42","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1007\/s00044-023-03153-4","volume":"32","author":"MA Langarizadeh","year":"2023","unstructured":"Langarizadeh, M. A., Ameri, A., Tavakoli, M. R., Abiri, A. & Forootanfar, H. The Trimethoxyphenyl (TMP) functional group: a versatile pharmacophore. Med. Chem. Res. 32, 2473\u20132500. https:\/\/doi.org\/10.1007\/s00044-023-03153-4 (2023).","journal-title":"Med. Chem. Res."},{"key":"36890_CR43","doi-asserted-by":"publisher","first-page":"111788","DOI":"10.1016\/j.ejmech.2019.111788","volume":"185","author":"AA Ghawanmeh","year":"2020","unstructured":"Ghawanmeh, A. A., Al-Bajalan, H. M., Mackeen, M. M., Alali, F. Q. & Chong, K. F. Recent developments on (-)-colchicine derivatives: synthesis and structure-activity relationship. Eur. J. Med. Chem. 185, 111788. https:\/\/doi.org\/10.1016\/j.ejmech.2019.111788 (2020).","journal-title":"Eur. J. Med. Chem."},{"key":"36890_CR44","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/s0300-9084(98)80004-7","volume":"80","author":"TF Imbert","year":"1998","unstructured":"Imbert, T. F. Discovery of podophyllotoxins. Biochimie 80, 207\u2013222. https:\/\/doi.org\/10.1016\/s0300-9084(98)80004-7 (1998).","journal-title":"Biochimie"},{"key":"36890_CR45","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3390\/molecules27051587","volume":"27","author":"S Tang","year":"2022","unstructured":"Tang, S., Zhou, Z., Jiang, Z., Zhu, W. & Qiao, D. Indole-Based tubulin inhibitors: Binding modes and SARs investigations. Molecules 27, 1587. https:\/\/doi.org\/10.3390\/molecules27051587 (2022).","journal-title":"Molecules"},{"key":"36890_CR46","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nature02393","volume":"428","author":"RBG Ravelli","year":"2004","unstructured":"Ravelli, R. B. G. et al. Insight into tubulin regulation from a complex with Colchicine and a stathmin-like domain. Nature 428, 198\u2013202. https:\/\/doi.org\/10.1038\/nature02393 (2004).","journal-title":"Nature"},{"key":"36890_CR47","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1021\/np1004278","volume":"73","author":"VV Semenov","year":"2010","unstructured":"Semenov, V. V. et al. Synthesis of antimitotic polyalkoxyphenyl derivatives of combretastatin using plant Allylpolyalkoxybenzenes. J. Nat. Prod. 73, 1796\u20131802. https:\/\/doi.org\/10.1021\/np1004278 (2010).","journal-title":"J. Nat. Prod."},{"key":"36890_CR48","doi-asserted-by":"publisher","first-page":"7877","DOI":"10.1021\/acs.jmedchem.8b00827","volume":"61","author":"Q Wang","year":"2018","unstructured":"Wang, Q. et al. Structural modification of the 3,4,5-Trimethoxyphenyl moiety in the tubulin inhibitor VERU-111 leads to improved antiproliferative activities. J. Med. Chem. 61, 7877\u20137891. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b00827 (2018).","journal-title":"J. Med. Chem."},{"key":"36890_CR49","doi-asserted-by":"publisher","first-page":"2200","DOI":"10.3390\/molecules29102200","volume":"29","author":"M J\u0119drzejczyk","year":"2024","unstructured":"J\u0119drzejczyk, M. et al. Novel combretastatin A-4 Analogs\u2014Design, Synthesis, and antiproliferative and Anti-Tubulin activity. Molecules 29, 2200. https:\/\/doi.org\/10.3390\/molecules29102200 (2024).","journal-title":"Molecules"},{"key":"36890_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40661-017-0058-5","volume":"5","author":"R Grisham","year":"2018","unstructured":"Grisham, R., Ky, B., Tewari, K. S., Chaplin, D. J. & Walker, J. Clinical trial experience with CA4P anticancer therapy: Focus on efficacy, cardiovascular adverse events, and hypertension management. Gynecol. Oncol. Res. Pract. 5, 1. https:\/\/doi.org\/10.1186\/s40661-017-0058-5 (2018).","journal-title":"Gynecologic Oncol. Res. Pract."},{"key":"36890_CR51","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.bmcl.2013.11.034","volume":"24","author":"CH Jeong","year":"2014","unstructured":"Jeong, C. H., Park, H. B., Jang, W. J., Jung, S. H. & Seo, Y. H. Discovery of hybrid Hsp90 inhibitors and their anti-neoplastic effects against gefitinib-resistant non-small cell lung cancer (NSCLC). Bioorg. Med. Chem. Lett. 24, 224\u2013227. https:\/\/doi.org\/10.1016\/j.bmcl.2013.11.034 (2014).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"36890_CR52","doi-asserted-by":"publisher","first-page":"7731","DOI":"10.1021\/acs.jafc.5b02011","volume":"63","author":"Y Li","year":"2015","unstructured":"Li, Y. et al. Hexamethoxylated monocarbonyl analogues of Curcumin cause G2\/M cell cycle arrest in NCI-H460 cells via Michael Acceptor-Dependent redox intervention. J. Agric. Food Chem. 63, 7731\u20137742. https:\/\/doi.org\/10.1021\/acs.jafc.5b02011 (2015).","journal-title":"J. Agric. Food Chem."},{"key":"36890_CR53","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1021\/acs.jmedchem.5b00037","volume":"58","author":"LY Ma","year":"2015","unstructured":"Ma, L. Y. et al. Design, Synthesis, and Structure\u2013Activity relationship of novel LSD1 inhibitors based on Pyrimidine\u2013Thiourea hybrids as Potent, orally active antitumor agents. J. Med. Chem. 58, 1705\u20131716. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00037 (2015).","journal-title":"J. Med. Chem."},{"key":"36890_CR54","doi-asserted-by":"publisher","first-page":"7900","DOI":"10.1021\/jm501177w","volume":"57","author":"AH Mohedas","year":"2014","unstructured":"Mohedas, A. H. et al. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J. Med. Chem. 57, 7900\u20137915. https:\/\/doi.org\/10.1021\/jm501177w (2014).","journal-title":"J. Med. Chem."},{"key":"36890_CR55","doi-asserted-by":"publisher","first-page":"4058","DOI":"10.1021\/jm401966m","volume":"57","author":"S Singh","year":"2014","unstructured":"Singh, S. et al. Design and synthesis of human ABCB1 (P-glycoprotein) inhibitors by peptide coupling of diverse chemical scaffolds on carboxyl and amino termini of (S)-valine-derived thiazole amino acid. J. Med. Chem. 57, 4058\u20134072. https:\/\/doi.org\/10.1021\/jm401966m (2014).","journal-title":"J. Med. Chem."},{"key":"36890_CR56","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/BF00684875","volume":"34","author":"CP Belani","year":"1994","unstructured":"Belani, C. P., Doyle, L. A. & Aisner, J. Etoposide: Current status and future perspectives in the management of malignant neoplasms. Cancer Chemother. Pharmacol. 34, 118\u2013126. https:\/\/doi.org\/10.1007\/BF00684875 (1994). Suppl.","journal-title":"Cancer Chemother. Pharmacol."},{"key":"36890_CR57","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2165\/00003088-198712040-00001","volume":"12","author":"PI Clark","year":"1987","unstructured":"Clark, P. I. & Slevin, M. L. The clinical Pharmacology of Etoposide and Teniposide. Clin. Pharmacokinet. 12, 223\u2013252. https:\/\/doi.org\/10.2165\/00003088-198712040-00001 (1987).","journal-title":"Clin. Pharmacokinet."},{"key":"36890_CR58","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3978\/j.issn.2218-6751.2016.01.13","volume":"5","author":"G Alvarado-Luna","year":"2016","unstructured":"Alvarado-Luna, G. & Morales-Espinosa, D. Treatment for small cell lung cancer, where are we now?\u2014a review. Transl. Lung Cancer Res. 5, 26\u201338. https:\/\/doi.org\/10.3978\/j.issn.2218-6751.2016.01.13 (2016).","journal-title":"Translational Lung Cancer Res."},{"key":"36890_CR59","unstructured":"O\u2019Dwyer, P. J. et al. Trimetrexate: Clinical development of a nonclassical antifolate. NCI Monogr. 105\u2013109 (1987)."},{"key":"36890_CR60","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1002\/ardp.201100169","volume":"345","author":"CH Zheng","year":"2012","unstructured":"Zheng, C. H. et al. Synthesis and biological evaluation of 1-Phenyl-1,2,3,4-dihydroisoquinoline compounds as tubulin polymerization inhibitors. Arch. Pharm. 345, 454\u2013462. https:\/\/doi.org\/10.1002\/ardp.201100169 (2012).","journal-title":"Arch. Pharm."},{"key":"36890_CR61","doi-asserted-by":"publisher","first-page":"5991","DOI":"10.3390\/ijms23115991","volume":"23","author":"M Zurlo","year":"2022","unstructured":"Zurlo, M. et al. Synergistic effects of a combined treatment of glioblastoma U251 cells with an anti-miR-10b-5p molecule and an antiCancer agent based on 1-(3\u2032,4\u2032,5\u2032-Trimethoxyphenyl)-2-Aryl-1H-Imidazole scaffold. Int. J. Mol. Sci. 23, 5991. https:\/\/doi.org\/10.3390\/ijms23115991 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"36890_CR62","doi-asserted-by":"publisher","first-page":"113826","DOI":"10.1016\/j.ejmech.2021.113826","volume":"226","author":"R Liu","year":"2021","unstructured":"Liu, R. et al. Design, synthesis and bioevaluation of 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d]imidazoles as tubulin polymerization inhibitors. Eur. J. Med. Chem. 226, 113826. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113826 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"36890_CR63","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s10593-015-1653-1","volume":"51","author":"GA Meshram","year":"2015","unstructured":"Meshram, G. A. & Vala, V. A. Synthesis, characterization, and antimicrobial activity of benzimidazole-derived Chalcones containing 1,3,4-oxadiazole moiety. Chem. Heterocycl. Compd. 51, 44\u201350 (2015).","journal-title":"Chem. Heterocycl. Compd."},{"key":"36890_CR64","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1021\/jm3014663","volume":"56","author":"DG Zhao","year":"2013","unstructured":"Zhao, D. G. et al. Synthesis and structure\u2013activity relationships of N-methyl-5,6,7-trimethoxylindoles as novel antimitotic and vascular disrupting agents. J. Med. Chem. 56, 1467\u20131477. https:\/\/doi.org\/10.1021\/jm3014663 (2013).","journal-title":"J. Med. Chem."},{"key":"36890_CR65","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.1007\/s00044-012-0428-9","volume":"22","author":"K Metwally","year":"2013","unstructured":"Metwally, K. et al. Structure\u2013activity relationship investigation of methoxy substitution on anticancer pyrimido[4,5-c]quinolin-1(2H)-ones. Med. Chem. Res. 22, 4481\u20134491. https:\/\/doi.org\/10.1007\/s00044-012-0428-9 (2013).","journal-title":"Med. Chem. Res."},{"key":"36890_CR66","doi-asserted-by":"publisher","first-page":"135662","DOI":"10.1016\/j.molstruc.2023.135662","volume":"1286","author":"NR Elejalde-Cadena","year":"2023","unstructured":"Elejalde-Cadena, N. R., Garc\u00eda-Olave, M., Mac\u00edas, M. A. & Portilla, J. Influence of halogen atoms and hydrogen bonds in the crystal structure of 1,2,4-trisubstituted imidazoles having haloaryl groups. J. Mol. Struct. 1286, 135662. https:\/\/doi.org\/10.1016\/j.molstruc.2023.135662 (2023).","journal-title":"J. Mol. Struct."},{"key":"36890_CR67","doi-asserted-by":"publisher","unstructured":"Mattiello, L., Rehim, S. S. A., Manic, G., & Vitale, I. Assessment of cell cycle progression and mitotic slippage by videomicroscopy. In Methods Cell Biology, Vol. 181 43\u201358 (Academic Press, 2024). https:\/\/doi.org\/10.1016\/bs.mcb.2023.03.004","DOI":"10.1016\/bs.mcb.2023.03.004"},{"key":"36890_CR68","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.molcel.2006.05.023","volume":"23","author":"C Lu","year":"2006","unstructured":"Lu, C. et al. Cell apoptosis: requirement of H2AX in DNA ladder formation but not for the activation of Caspase-3. Mol. Cell. 23, 121\u2013132. https:\/\/doi.org\/10.1016\/j.molcel.2006.05.023 (2006).","journal-title":"Mol. Cell"},{"key":"36890_CR69","doi-asserted-by":"publisher","unstructured":"Podhorecka, M., Skladanowski, A. & Bozko, P. H. A. X. Phosphorylation its role in DNA damage response and cancer therapy. J. Nucleic Acids. https:\/\/doi.org\/10.4061\/2010\/920161 (2010).","DOI":"10.4061\/2010\/920161"},{"key":"36890_CR70","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.trecan.2017.02.001","volume":"3","author":"SF Bakhoum","year":"2017","unstructured":"Bakhoum, S. F., Kabeche, L., Compton, D. A., Powell, S. N. & Bastians, H. Mitotic DNA damage response: At the crossroads of structural and numerical cancer chromosome instabilities. Trends Cancer. 3, 225\u2013234. https:\/\/doi.org\/10.1016\/j.trecan.2017.02.001 (2017).","journal-title":"Trends Cancer"},{"key":"36890_CR71","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.3390\/ijms18091979","volume":"18","author":"A Georgoulis","year":"2017","unstructured":"Georgoulis, A., Vorgias, C. E., Chrousos, G. P. & Rogakou, E. P. Genome instability and \u03b3H2AX. Int. J. Mol. Sci. 18, 1979. https:\/\/doi.org\/10.3390\/ijms18091979 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"36890_CR72","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol. 35, 495\u2013516. https:\/\/doi.org\/10.1080\/01926230701320337 (2007).","journal-title":"Toxicol. Pathol."},{"key":"36890_CR73","doi-asserted-by":"publisher","first-page":"732","DOI":"10.3390\/cells14100732","volume":"14","author":"S Shah","year":"2025","unstructured":"Shah, S. & D\u2019Souza, G. G. M. Modeling tumor microenvironment complexity in vitro: spheroids as physiologically relevant tumor models and strategies for their analysis. Cells 14, 732. https:\/\/doi.org\/10.3390\/cells14100732 (2025).","journal-title":"Cells"},{"key":"36890_CR74","doi-asserted-by":"publisher","first-page":"T97","DOI":"10.1530\/ERC-17-0147","volume":"24","author":"B Cheng","year":"2017","unstructured":"Cheng, B. & Crasta, K. Consequences of mitotic slippage for antimicrotubule drug therapy. Endocr. Relat. Cancer. 24, T97\u2013T106. https:\/\/doi.org\/10.1530\/ERC-17-0147 (2017).","journal-title":"Endocr. Relat. Cancer"},{"key":"36890_CR75","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1080\/15384101.2018.1559557","volume":"18","author":"D Sinha","year":"2019","unstructured":"Sinha, D., Duijf, P. H. G. & Khanna, K. K. Mitotic slippage: An old Tale with a new twist. Cell. Cycle. 18, 7\u201315. https:\/\/doi.org\/10.1080\/15384101.2018.1559557 (2019).","journal-title":"Cell. Cycle"},{"key":"36890_CR76","doi-asserted-by":"publisher","first-page":"42717","DOI":"10.1038\/srep42717","volume":"7","author":"A Daina","year":"2017","unstructured":"Daina, A., Michielin, O. & Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717. https:\/\/doi.org\/10.1038\/srep42717 (2017).","journal-title":"Sci. Rep."},{"key":"36890_CR77","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nrd4609","volume":"14","author":"MJ Waring","year":"2015","unstructured":"Waring, M. J. et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov. 14, 475\u2013486. https:\/\/doi.org\/10.1038\/nrd4609 (2015).","journal-title":"Nat. Rev. Drug Discovery"},{"key":"36890_CR78","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","volume":"1","author":"CA Lipinski","year":"2004","unstructured":"Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today: Technol. 1, 337\u2013341. https:\/\/doi.org\/10.1016\/j.ddtec.2004.11.007 (2004).","journal-title":"Drug Discovery Today: Technol."},{"key":"36890_CR79","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1021\/jm020017n","volume":"45","author":"DF Veber","year":"2002","unstructured":"Veber, D. F. et al. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45, 2615\u20132623. https:\/\/doi.org\/10.1021\/jm020017n (2002).","journal-title":"J. Med. Chem."},{"key":"36890_CR80","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.chembiol.2014.08.013","volume":"21","author":"BC Doak","year":"2014","unstructured":"Doak, B. C., Over, B., Giordanetto, F. & Kihlberg, J. Oral druggable space beyond the rule of 5: Insights from drugs and clinical candidates. Chem. Biol. 21, 1115\u20131142. https:\/\/doi.org\/10.1016\/j.chembiol.2014.08.013 (2014).","journal-title":"Chem. Biol."},{"key":"36890_CR81","unstructured":"Buchwald, P. Drug-Like Properties Concepts, Structure Design and Methods from ADME To Toxicity Optimization (Academic, 2016)."},{"key":"36890_CR82","doi-asserted-by":"publisher","first-page":"17590","DOI":"10.1038\/s41598-025-02106-8","volume":"15","author":"G Pranaityt\u0117","year":"2025","unstructured":"Pranaityt\u0117, G. et al. Exploration of 1-(2,4-difluorophenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives effect on triple-negative breast, prostate cancer and melanoma cell 2D and 3D cultures. Sci. Rep. 15, 17590. https:\/\/doi.org\/10.1038\/s41598-025-02106-8 (2025).","journal-title":"Sci. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-36890-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-36890-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-36890-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:05:13Z","timestamp":1770977113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-36890-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["36890"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-36890-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"assertion":[{"value":"4 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6271"}}