{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:12:30Z","timestamp":1788963150866,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-73-10062"],"award-info":[{"award-number":["21-73-10062"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The present work focuses on the study of the aggregation and complexing properties of calixarenes as potential DNA condensation agents for gene delivery. In the current study, 1,4-triazole derivatives of calix[4]arenes 7 and 8 containing monoammonium fragments were synthesized. The synthesized compound\u2019s structure was characterized by using various spectroscopic techniques (FTIR, HRESI MS, \u00b9H NMR and \u00b9\u00b3C NMR). The interactions between a series of calix[4]arene-containing aminotriazole groups (triazole-containing macrocycles with diethylenetriammonium fragments (3 and 4) and triazole-containing macrocycles with monoammonium fragments (7 and 8)) and calf thymus DNA were carried out via UV absorption, fluorescence spectroscopy, dynamic light scattering and zeta potential measurements. The role of the binding forces of calixarene\u2013DNA complexes was analyzed. Photophysical and morphological studies revealed the interaction of the calixarenes 3, 4 and 8 with ct-DNA, which transformed the fibrous structure of ct-DNA to completely condensed compact structures that are 50 nm in diameter. The cytotoxic properties of calixarenes 3, 4, 7 and 8 against cancerous cells (MCF7, PC-3) as well as a healthy cell line (HSF) were investigated. Compound 4 was found to have the highest toxic effect on MCF7 breast adenocarcinoma (IC50 3.3 \u03bcM).<\/jats:p>","DOI":"10.3390\/ph16050699","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T08:12:11Z","timestamp":1683274331000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Aggregation, Cytotoxicity and DNA Binding in a Series of Calix[4]arene Amphiphile Containing Aminotriazole Groups"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-3300","authenticated-orcid":false,"given":"Diana","family":"Mironova","sequence":"first","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor","family":"Makarov","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islamiya","family":"Bilyukova","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevser","family":"Akyol","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8796-4352","authenticated-orcid":false,"given":"Elsa","family":"Sultanova","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Evtugyn","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Analytical Microscopy, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damir","family":"Davletshin","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvina","family":"Gilyazova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-0032","authenticated-orcid":false,"given":"Emil","family":"Bulatov","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-3340","authenticated-orcid":false,"given":"Vladimir","family":"Burilov","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7106-6777","authenticated-orcid":false,"given":"Svetlana","family":"Solovieva","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Str., 420088 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Antipin","sequence":"additional","affiliation":[{"name":"Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Neri, P.S., Sessler, J.L., and Wang, M.-X. (2016). Calixarenes and Beyond, Springer.","DOI":"10.1007\/978-3-319-31867-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ijbiomac.2021.02.010","article-title":"Immobilized lipases-based nano-biocatalytic systems\u2014A versatile platform with incredible biotechnological potential","volume":"175","author":"Bilal","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Basilotta, R., Mannino, D., Filippone, A., Casili, G., Prestifilippo, A., Colarossi, L., Raciti, G., Esposito, E., and Campolo, M. (2021). Role of Calixarene in Chemotherapy Delivery Strategies. Molecules, 26.","DOI":"10.3390\/molecules26133963"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112984","DOI":"10.1016\/j.ejmech.2020.112984","article-title":"Design, synthesis and evaluation of calix[4]arene-based carbonyl amide derivatives with antitumor activities","volume":"210","author":"An","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shurpik, D.N., Padnya, P.L., Stoikov, I.I., and Cragg, P.J. (2020). Antimicrobial Activity of Calixarenes and Related Macrocycles. Molecules, 25.","DOI":"10.3390\/molecules25215145"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"816741","DOI":"10.3389\/fchem.2022.816741","article-title":"Membrane-Active Antibacterial Agents Based on Calix[4]arene Derivatives: Synthesis and Biological Evaluation","volume":"10","author":"Fang","year":"2022","journal-title":"Front. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3389\/fchem.2018.00210","article-title":"Synthesis, in-Vitro and in Silico Studies of Azo-Based Calix[4]arenes as Antibacterial Agent and Neuraminidase Inhibitor: A New Look Into an Old Scaffold","volume":"6","author":"Ali","year":"2018","journal-title":"Front. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40543-017-0111-3","article-title":"Synthesis and investigation of antimicrobial properties of pyrrolidine appended calix[4]arene","volume":"8","author":"Muneer","year":"2017","journal-title":"J. Anal. Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/jccs.201900425","article-title":"Synthesis, antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives","volume":"67","year":"2020","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1021\/bc700411w","article-title":"Calix[4]arene Decorated with Four Tn Antigen Glycomimetic Units and P3CS Immunoadjuvant: Synthesis, Characterization, and Anticancer Immunological Evaluation","volume":"19","author":"Geraci","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1039\/C4OB02611J","article-title":"Xanthenones: Calixarenes-catalyzed syntheses, anticancer activity and QSAR studies","volume":"13","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s00044-021-02813-7","article-title":"Synthesis of new calix[4]arene derivatives and evaluation of their cytotoxic activity","volume":"31","author":"Oguz","year":"2022","journal-title":"Med. Chem. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ejmech.2014.10.048","article-title":"Novel analogs of antitumor agent calixarene 0118: Synthesis, cytotoxicity, click labeling with 2-[18F]fluoroethylazide, and in vivo evaluation","volume":"89","author":"Dings","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14528","DOI":"10.1021\/ja0634425","article-title":"DNA Condensation and Cell Transfection Properties of Guanidinium Calixarenes:\u2009 Dependence on Macrocycle Lipophilicity, Size, and Conformation","volume":"128","author":"Sansone","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"433","DOI":"10.6060\/mhc161180b","article-title":"Polycationic Derivatives of p-tert-Butylthiacalix[4]arene in 1,3-alternate Stereoisomeric Form: New DNA Condensing Agents","volume":"9","author":"Ibragimova","year":"2016","journal-title":"Macroheterocycles"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Espa\u00f1ol, E.S., and Villamil, M.M. (2019). Calixarenes: Generalities and Their Role in Improving the Solubility, Biocompatibility, Stability, Bioavailability, Detection, and Transport of Biomolecules. Biomolecules, 9.","DOI":"10.3390\/biom9030090"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112724","DOI":"10.1016\/j.molliq.2020.112724","article-title":"Self-aggregation in aqueous solution of amphiphilic cationic calix[4]arenes. Potential use as vectors and nanocarriers","volume":"304","author":"Ostos","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"626467","DOI":"10.3389\/fchem.2020.626467","article-title":"Binding Affinity and Driving Forces for the Interaction of Calixarene-Based Micellar Aggregates with Model Antibiotics in Neutral Aqueous Solution","volume":"8","author":"Migliore","year":"2021","journal-title":"Front. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8465","DOI":"10.1021\/ja035636f","article-title":"Remarkably Size-Regulated Cell Invasion by Artificial Viruses. Saccharide-Dependent Self-Aggregation of Glycoviruses and Its Consequences in Glycoviral Gene Delivery","volume":"125","author":"Nakai","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8522","DOI":"10.1021\/la801083h","article-title":"Amino-Substituted Amphiphilic Calixarenes: Self-Assembly and Interactions with DNA","volume":"24","author":"Shahgaldian","year":"2008","journal-title":"Langmuir"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5581","DOI":"10.1039\/b926025k","article-title":"Cell transfection using layer-by-layer (LbL) coated calixarene-based solid lipid nanoparticles (SLNs)","volume":"46","author":"Nault","year":"2010","journal-title":"Chem. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1111\/j.2042-7158.2012.01518.x","article-title":"Preparation and physicochemical characterization of a novel paclitaxel-loaded amphiphilic aminocalixarene nanoparticle platform for anticancer chemotherapy","volume":"64","author":"Weeden","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1134\/S1990793119030163","article-title":"New Amphiphilic Calix[4]Arene Derivatives with 4,5-Dicarboxytriazolyl Fragments: Synthesis and Use in Micellar Catalysis","volume":"13","author":"Fatykhova","year":"2019","journal-title":"Russ. J. Phys. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Burilov, V., Makarov, E., Mironova, D., Sultanova, E., Bilyukova, I., Akyol, K., Evtugyn, V., Islamov, D., Usachev, K., and Mukhametzyanov, T. (2022). Calix[4]arene Polyamine Triazoles: Synthesis, Aggregation and DNA Binding. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314889"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1021\/ja00307a038","article-title":"Calixarenes. 13. The conformational properties of calix[4]arenes, calix[6]arenes, calix[8]arenes, and oxacalixarenes","volume":"107","author":"Gutsche","year":"1985","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0021-9797(02)00082-6","article-title":"On the determination of the critical micelle concentration by the pyrene 1:3 ratio method","volume":"258","author":"Aguiar","year":"2003","journal-title":"J. Colloid Interface Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jcis.2022.10.018","article-title":"The melting curves of calf thymus-DNA are buffer specific","volume":"630","author":"Mura","year":"2023","journal-title":"J. Colloid Interface Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.ijbiomac.2017.03.136","article-title":"Characterization of the groove binding between di-(2-ethylhexyl) phthalate and calf thymus DNA","volume":"101","author":"Li","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lakowicz, J. (2006). Principles of Fluorescence Spectroscopy, Springer.","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1021\/bi00514a017","article-title":"Thermodynamics of protein association reactions: Forces contributing to stability","volume":"20","author":"Ross","year":"1981","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23333","DOI":"10.1021\/acsami.7b04317","article-title":"DNA Condensation Induced by a Star-Shaped Hexameric Cationic Surfactant","volume":"9","author":"Fan","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1016\/j.tet.2015.07.077","article-title":"Cell proliferation effects of calix[4]arene derivatives","volume":"71","author":"Santos","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1039\/b903635k","article-title":"Preorganized macromolecular gene delivery systems: Amphiphilic \u03b2-cyclodextrin \u201cclick clusters\u201d","volume":"7","author":"Mellet","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.15227\/orgsyn.068.0234","article-title":"p-tert-Butylcalix[4]arene","volume":"68","author":"Gutsche","year":"1990","journal-title":"Org. Synth."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1908435","DOI":"10.1002\/adma.201908435","article-title":"A General Hypoxia-Responsive Molecular Container for Tumor-Targeted Therapy","volume":"32","author":"Zhang","year":"2020","journal-title":"Adv. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/0006-3002(60)90834-9","article-title":"The u.v.-absorption of calf-thymus DNA","volume":"42","author":"Inman","year":"1960","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:29:45Z","timestamp":1760124585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ph16050699"],"URL":"https:\/\/doi.org\/10.3390\/ph16050699","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]}}}