{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:49:39Z","timestamp":1791082179211,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at King Khalid University","award":["R.G.P. 2\/78\/43"],"award-info":[{"award-number":["R.G.P. 2\/78\/43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1\u2013C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand\u2019s reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich\u2013Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C27H23Cl2CoFN5O3 exhibited profound anti-proliferative activity against the EAC cell line with a significant IC50 value of 10 \u00b5m when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF165, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg\/kg of two doses and tumor parameters were evaluated.<\/jats:p>","DOI":"10.3390\/ph16010125","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T01:31:15Z","timestamp":1673832675000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel Benzimidazole Derived Imine Ligand and Its Co(III) and Cu(II) Complexes as Anticancer Agents: Chemical Synthesis, DFT Studies, In Vitro and In Vivo Biological Investigations"],"prefix":"10.3390","volume":"16","author":[{"given":"Prakasha","family":"G","sequence":"first","affiliation":[{"name":"Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. D.","family":"Revanasiddappa","sequence":"additional","affiliation":[{"name":"Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayalakshmi","family":"B","sequence":"additional","affiliation":[{"name":"Department of Botany, Government College for Women, Mandya 571 401, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar B.","family":"T","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shimoga 577 203, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-139X","authenticated-orcid":false,"given":"Chandan","family":"Shivamallu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570 015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant M.","family":"Viswanath","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysore 570 015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-3703","authenticated-orcid":false,"given":"Raghu Ram","family":"Achar","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570 015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-5149","authenticated-orcid":false,"given":"Ekaterina","family":"Silina","sequence":"additional","affiliation":[{"name":"Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Stupin","sequence":"additional","affiliation":[{"name":"Department of Hospital Surgery, N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Manturova","sequence":"additional","affiliation":[{"name":"Department of Hospital Surgery, N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Shati","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-3539","authenticated-orcid":false,"given":"Mohammad Y.","family":"Alfaifi","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-3215","authenticated-orcid":false,"given":"Serag Eldin I.","family":"Elbehairi","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"},{"name":"Cell Culture Lab, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company), 51 Wezaret El-Zeraa St., Agouza, Giza 22311, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-1046","authenticated-orcid":false,"given":"Sanja J.","family":"Armakovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8049-9969","authenticated-orcid":false,"given":"Stevan","family":"Armakovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Department of Physics, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-3933","authenticated-orcid":false,"given":"Shiva Prasad","family":"Kollur","sequence":"additional","affiliation":[{"name":"School of Physical Sciences, Amrita Vishwa Vidyapeetham, Mysuru Campus, Mysuru 570 026, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2147\/DDDT.S119488","article-title":"Metal complexes in cancer therapy an update from drug design perspective","volume":"11","author":"Ndagi","year":"2017","journal-title":"Drug Des. 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