Evaluation of the antitumor activity of a series of the pincer-type metallocomplexes produced from isonicotinohydrazide derivative

• Published in: Journal of inorganic biochemistry Vol. 223; p. 111525
• Main Authors: Saygıdeğer Demir, Burcu, Mahmoudi, Ghodrat, Sezan, Aycan, Derinöz, Ezgi, Nas, Eylem, Saygideger, Yasemin, Zubkov, Fedor I., Zangrando, Ennio, Safin, Damir A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Crystal structure; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytotoxicity; Drug Screening Assays, Antitumor; Humans; Isoniazid - analogs & derivatives; Isoniazid - pharmacology; Isonicotinohydrazone; Molecular Structure; Pincer type complexes; Tumor Suppressor Protein p53 - metabolism; Antitumor activity; Cytotoxicity; Pincer type complexes; Isonicotinohydrazone; Apoptosis; Crystal structure
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111525

In this work we report on the antitumor properties of a series of pincer-type metallocomplexes [Hg2(HL-keto)Cl4]n (1), [Hg(HL-keto)I2] (2) and [Mn(HL-zwitterion)Cl2]∙MeOH (3∙MeOH), derived from N′-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL) and corresponding metal salts. The Hg(II) and Mn(II) salts are chelated by the keto (HL-keto) or zwitterionic (HL-zwitterion) form of HL, respectively. The cytotoxic effects of these compounds have been accessed against lung adenocarcinoma (A549) and hepatocellular carcinoma (HepG2 and Huh7) cell lines. Complexes 1 and 2 were found to be most efficient against the cell line Huh7 with IC50 value of 2.56 and 9.90 μM, respectively, while they exhibit moderate activity towards cell lines A549 and HepG2, as evidenced from IC50 values in the range 27.98–56.99 μM. Complex 3∙MeOH is less efficient towards all the three cell lines with relatively high IC50 values. The mechanisms of the metallocomplexes killing the aforementioned cells were elucidated by flow cytometry, colony formation and polymerase chain reaction (PCR) analysis of apoptosis related expression of the genes. The results of the cytotoxic effects and antitumor activity on different cell lines are affected by the metal nature and the presence of the coordinated halide. We report antitumor properties of [Hg2(HL-keto)Cl4]n (1), [Hg(HL-keto)I2] (2) and [Mn(HL-zwitterion)Cl2]∙MeOH (3∙MeOH), fabricated from N′-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL). The Hg(II) and Mn(II) salts are chelated by the keto (HL-keto) or zwitterionic (HL-zwitterion) form of HL, respectively. The cytotoxic effects of the compounds were examined in the A549, HepG2 and Huh7 cell lines. [Display omitted] •New HgCl2- (1), HgI2- (2) and MnCl2-based (3) complexes were obtained from HL.•HL denotes N′-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide.•Complexes showed cytotoxic effects towards the A549, HepG2 and Huh7 cancer cells.•Complexes diminish colonization of the HepG2 and Huh7 cells.•Complexes perform antitumoral activity by interacting with DNA.