{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:03:26Z","timestamp":1787069006030,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia","award":["IFKSURG-2-902"],"award-info":[{"award-number":["IFKSURG-2-902"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>One of medicinal chemistry\u2019s top priorities is the discovery of new molecules with anticancer potential. Compounds that interact with DNA are an intriguing family of chemotherapeutic medications used to treat cancer. Studies in this area have uncovered a plethora of potential anticancer medicines, such as groove binding, alkylating, and intercalator compounds. The anticancer activity of DNA intercalators (molecules that intercalate between DNA base pairs) has drawn special interest. The current study investigated the promising anticancer drug 1,3,5-Tris(4-carboxyphenyl)benzene (H3BTB) against breast and cervical cancer cell lines. In addition, 1,3,5-Tris(4-carboxyphenyl)benzene binds to DNA by groove binding. The binding of H3BTB to DNA was found to be significant which unwinds the DNA helix. Considerable electrostatic and non-electrostatic contributions were present in the binding\u2019s free energy. The cytotoxic potential of H3BTB is effectively demonstrated by the computational study outcomes, which include molecular docking and molecular dynamics (MD) simulations. The minor groove binding for the H3BTB\u2013DNA complex is supported by molecular docking research. This study will promote empirical investigation into the synthesis of metallic and non-metallic H3BTB derivatives and their potential use as bioactive molecules for the treatment of cancer.<\/jats:p>","DOI":"10.3390\/cells12081120","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:15:57Z","timestamp":1681096557000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Molecular Spectroscopy Evidence of 1,3,5-Tris(4-carboxyphenyl)benzene Binding to DNA: Anticancer Potential along with the Comparative Binding Profile of Intercalation via Modeling Studies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-2685","authenticated-orcid":false,"given":"Tanveer A.","family":"Wani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-0841","authenticated-orcid":false,"given":"Seema","family":"Zargar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"K\u00fcpeli Akkol, E., Gen\u00e7, Y., Karpuz, B., Sobarzo-S\u00e1nchez, E., and Capasso, R. (2020). Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers, 12.","DOI":"10.3390\/cancers12071959"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ccr.2016.04.019","article-title":"The application of mesoporous silica nanoparticle family in cancer theranostics","volume":"319","author":"Feng","year":"2016","journal-title":"Coord. Chem. Chem. Rev."},{"key":"ref_3","first-page":"141","article-title":"Drug resistance and combating drug resistance in cancer","volume":"2","author":"Wang","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s10495-015-1169-2","article-title":"Cell death mechanisms of plant-derived anticancer drugs: Beyond apoptosis","volume":"20","author":"Hmadi","year":"2015","journal-title":"Apoptosis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrc2342","article-title":"DNA repair pathways as targets for cancer therapy","volume":"8","author":"Helleday","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Arshad, N., Mir, M.I., Perveen, F., Javed, A., Javaid, M., Saeed, A., Channar, P.A., Farooqi, S.I., Alkahtani, S., and Anwar, J. (2022). Investigations on anticancer potentials by DNA binding and cytotoxicity studies for newly synthesized and characterized imidazolidine and thiazolidine-based isatin derivatives. Molecules, 27.","DOI":"10.3390\/molecules27020354"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13909","DOI":"10.1039\/D1NJ02419A","article-title":"Novel 1,3,5-triazine-based pyrazole derivatives as potential antitumor agents and EFGR kinase inhibitors: Synthesis, cytotoxicity, DNA binding, molecular docking and DFT studies","volume":"45","author":"Raghu","year":"2021","journal-title":"New J. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101323","DOI":"10.1016\/j.jscs.2021.101323","article-title":"Molecular docking analysis and spectroscopic investigations of zinc (II), nickel (II) N-phthaloyl-\u03b2-alanine complexes for DNA binding: Evaluation of antibacterial and antitumor activities","volume":"25","author":"Arshad","year":"2021","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nosrati, M., and Roushani, M. (2022). Three-dimensional modeling of streptomycin binding single-stranded DNA for aptamer-based biosensors, a molecular dynamics simulation approach. J. Biomol. Struct. Dyn., 1\u201310.","DOI":"10.1080\/07391102.2022.2050945"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Alsahli, M.A., Almatroudi, A., Verma, A.K., Aloliqi, A., Allemailem, K.S., Khan, A.A., and Rahmani, A.H. (2021). Potential therapeutic targets of quercetin, a plant flavonol, and its role in the therapy of various types of cancer through the modulation of various cell signaling pathways. Molecules, 26.","DOI":"10.3390\/molecules26051315"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.2174\/1381612822666160325152200","article-title":"Current understanding of HSP90 as a novel therapeutic target: An emerging approach for the treatment of cancer","volume":"22","author":"Haque","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.semcancer.2015.09.015","article-title":"Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis","volume":"36","author":"Heo","year":"2016","journal-title":"Semin. Cancer Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1016\/j.ejca.2013.07.149","article-title":"miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway","volume":"49","author":"Wang","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41420-020-00349-0","article-title":"The caspase-3\/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer","volume":"6","author":"Jiang","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.tins.2012.06.004","article-title":"Caspase-3 in the central nervous system: Beyond apoptosis","volume":"35","author":"Sheng","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/1389450114666140106101412","article-title":"Targeting tumor suppressor p53 for cancer therapy: Strategies, challenges and opportunities","volume":"15","author":"Hong","year":"2014","journal-title":"Curr. Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107720","DOI":"10.1016\/j.pharmthera.2020.107720","article-title":"Current developments of targeting the p53 signaling pathway for cancer treatment","volume":"220","author":"Huang","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1593\/tlo.09250","article-title":"Targeting p53 for novel anticancer therapy","volume":"3","author":"Wang","year":"2010","journal-title":"Transl. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Antonijevic, M., Rochais, C., and Dallemagne, P. (2023). C3-Symmetric Ligands in Drug Design: When the Target Controls the Aesthetics of the Drug. Molecules, 28.","DOI":"10.3390\/molecules28020679"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15172","DOI":"10.1021\/acs.inorgchem.8b02445","article-title":"Controlled Dissociation of Iron and Cyclopentadienyl from a Diiron Complex with a Bridging C3 Ligand Triggered by One-Electron Reduction","volume":"57","author":"Agonigi","year":"2018","journal-title":"Inorg. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1039\/P29880001251","article-title":"New trigonal lattice hosts: Stoicheiometric crystal inclusions of laterally trisubstituted benzenes\u2014X-ray crystal structure of 1, 3, 5-tris-(4-carboxyphenyl) benzene dimethylformamide","volume":"7","author":"Weber","year":"1988","journal-title":"J. Chem. Soc. Perkin Trans. 2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10829","DOI":"10.1021\/jp057553m","article-title":"Solvent induced polymorphism in supramolecular 1, 3, 5-benzenetribenzoic acid monolayers","volume":"110","author":"Kampschulte","year":"2006","journal-title":"J. Phys. Chem. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1134\/S2070205122010117","article-title":"Adsorption Properties of a Functional Porous Material Based on a Zn\u2013BTB Metal\u2013Organic Framework Structure","volume":"58","author":"Khyazeva","year":"2022","journal-title":"Prot. Met. Phys. Chem. Surfaces."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1021\/ic402481b","article-title":"Construction of Two Microporous Metal\u2013Organic Frameworks with flu and pyr Topologies Based on Zn4 (\u03bc3-OH) 2 (CO2) 6 and Zn6 (\u03bc6-O)(CO2) 6 Secondary Building Units","volume":"53","author":"Li","year":"2014","journal-title":"Inorg. Chemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1134\/S2070205120060222","article-title":"Zr-based metal\u2013organic nanoporous adsorbents of high density for methane storage","volume":"56","author":"Solovtsova","year":"2020","journal-title":"Prot. Met. Phys. Chem. Surf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119082","DOI":"10.1016\/j.saa.2020.119082","article-title":"DFT calculations towards the geometry optimization, electronic structure, infrared spectroscopy and UV\u2013vis analyses of Favipiravir adsorption on the first-row transition metals doped fullerenes; a new strategy for COVID-19 therapy","volume":"247","author":"Rad","year":"2021","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bilal, M.S., Ejaz, S.A., Zargar, S., Akhtar, N., Wani, T.A., Riaz, N., Aborode, A.T., Siddique, F., Altwaijry, N., and Alkahtani, H.M. (2022). Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR: Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies. Biomolecules, 12.","DOI":"10.3390\/biom12111612"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0022-1759(90)90159-S","article-title":"Quantification of proliferative and suppressive responses of human T lymphocytes following ConA stimulation","volume":"126","author":"Otto","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132666","DOI":"10.1016\/j.molstruc.2022.132666","article-title":"Exploring Interaction Dynamics of Designed Organic Charge Transfer Complex of 6-Aminoindole and Chloranilic Acid: Spectrophotometric, Characterization, Computational, Antimicrobial, and DNA Binding Properties","volume":"1258","author":"Manojkumar","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.molliq.2015.11.002","article-title":"DNA binding and dispersion activities of titanium dioxide nanoparticles with UV\/vis spectrophotometry, fluorescence spectroscopy and physicochemical analysis at physiological temperature","volume":"213","author":"Patel","year":"2016","journal-title":"J. Mol. Liq."},{"key":"ref_32","unstructured":"Caricato, M., Frisch, M.J., Hiscocks, J., and Frisch, M.J. (2009). Gaussian 09: IOps Reference, Gaussian."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/9780470125847.ch5","article-title":"Density functional methods in biomolecular modeling","volume":"7","year":"1996","journal-title":"Rev. Comput. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0009-2614(00)00488-7","article-title":"Application of quantum chemical descriptor in quantitative structure activity and structure property relationship","volume":"323","author":"Thanikaivelan","year":"2000","journal-title":"Chem. Phys. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1021\/jp9703768","article-title":"A quantum chemical view of density functional theory","volume":"101","author":"Baerends","year":"1997","journal-title":"J. Phys. Chem. A"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1039\/b508541a","article-title":"Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy","volume":"7","author":"Weigend","year":"2005","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1063\/1.463096","article-title":"Fully optimized contracted Gaussian basis sets for atoms Li to Kr","volume":"97","author":"Horn","year":"1992","journal-title":"J. Chem. Phys."},{"key":"ref_38","unstructured":"Dennington, R., Keith, T.A., and Millam, J.M. (2019). GaussView, Semichem Inc.. Version 6."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Morris, G.M., and Lim-Wilby, M. (2008). Molecular Modeling of Proteins, Springer.","DOI":"10.1007\/978-1-59745-177-2_19"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-022-10253-5","article-title":"Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach","volume":"12","author":"Aziz","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_42","first-page":"37","article-title":"Molecular dynamics simulations: Advances and applications","volume":"8","author":"Hospital","year":"2015","journal-title":"Adv. Appl. Bioinform. Chem. AABC"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1021\/ct900587b","article-title":"Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field","volume":"6","author":"Shivakumar","year":"2010","journal-title":"J. Chem. Theory Comput."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant pressure molecular dynamics algorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J. Chem. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical dynamics: Equilibrium phase-space distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys. Rev. A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6885","DOI":"10.1021\/j100078a035","article-title":"A multiple-time-step molecular dynamics algorithm for macromolecules","volume":"98","author":"Humphreys","year":"1994","journal-title":"J. Phys. Chem. A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/08927029408022004","article-title":"A comparison of particle-particle, particle-mesh and Ewald methods for calculating electrostatic interactions in periodic molecular systems","volume":"14","author":"Luty","year":"1994","journal-title":"Mol. Simul."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.fct.2010.12.010","article-title":"Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines","volume":"49","author":"Fauzi","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Saeed, A., Ejaz, S.A., Saeed, M., Channar, P.A., Aziz, M., Fayyaz, A., Zargar, S., Wani, T.A., Alanazi, H., and Alharbi, M. (2023). Synthesis, Biochemical Characterization, and in-Silico Investigations of Acyl-3-(Ciprofloxacinyl) Thioureas as Inhibitors of Carbonic Anhydrase-II. Polycycl. Aromat. Compounds, 1\u201319.","DOI":"10.1080\/10406638.2022.2157027"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29354","DOI":"10.1039\/D1RA04101K","article-title":"Deciphering the interaction of flavones with calf thymus DNA and octamer DNA sequence (CCAATTGG) 2","volume":"11","author":"Kumar","year":"2021","journal-title":"RSC Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49404","DOI":"10.1039\/C7RA10283F","article-title":"Synthesis and crystal structure of new monometallic Ni (II) and Co (II) complexes with an asymmetrical aroylhydrazone: Effects of the complexes on DNA\/protein binding property, molecular docking, and in vitro anticancer activity","volume":"7","author":"Li","year":"2017","journal-title":"RSC Adv."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zargar, S., Wani, T.A., Alsaif, N.A., and Khayyat, A.I.A. (2022). A Comprehensive Investigation of Interactions between Antipsychotic Drug Quetiapine and Human Serum Albumin Using Multi-Spectroscopic, Biochemical, and Molecular Modeling Approaches. Molecules, 27.","DOI":"10.3390\/molecules27082589"},{"key":"ref_53","first-page":"555","article-title":"An overview of the optical and electrochemical methods for detection of DNA\u2013drug interactions","volume":"61","year":"2014","journal-title":"Acta Chim. Slov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109707","DOI":"10.1016\/j.cbi.2021.109707","article-title":"Exploring the binding mechanism and adverse toxic effects of persistent organic pollutant (dicofol) to human serum albumin: A biophysical, biochemical and computational approach","volume":"350","author":"Zargar","year":"2021","journal-title":"Chem.-Biol. Interact."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.17159\/0379-4350\/2020\/v73a7","article-title":"A spectroscopic, thermodynamic and molecular docking study of the binding mechanism of dapoxetine with calf thymus DNA","volume":"73","author":"Alsaif","year":"2020","journal-title":"S. Afr. J. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1021\/bm2017959","article-title":"Molecular spectroscopy evidence of berberine binding to DNA: Comparative binding and thermodynamic profile of intercalation","volume":"13","author":"Li","year":"2012","journal-title":"Biomacromolecules"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:56Z","timestamp":1760123576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,10]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cells12081120"],"URL":"https:\/\/doi.org\/10.3390\/cells12081120","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,10]]}}}