Comparative in vitro Studies of the Topoisomerase I Inhibition and Anticancer Activities of Metallated N‐Confused Porphyrins and Metallated Porphyrins

• Published in: ChemMedChem 2020-04, Vol.15 (7), p.632-642
• Main Authors: Halder, Nyancy, Dzhemileva, Lilya U., Ramazanov, Ilfir R., D'yakonov, Vladimir A., Dzhemilev, Usein M., Rath, Harapriya
• Format: Article
• Language: English
• Subjects: anticancer agents; Anticancer properties; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cu−N confused porphyrins; Cytotoxicity; DNA Damage; DNA topoisomerase; DNA Topoisomerases, Type I - metabolism; Drug Screening Assays, Antitumor; Humans; in vitro studies; Metalloporphyrins - chemical synthesis; Metalloporphyrins - chemistry; Metalloporphyrins - pharmacology; Molecular docking; Molecular Structure; N-confused porphyrins; Porphyrins; Synthesis; topoisomerase I inhibitors; Topoisomerase I Inhibitors - chemical synthesis; Topoisomerase I Inhibitors - chemistry; Topoisomerase I Inhibitors - pharmacology; Tumor cell lines
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201900633

Using the original approach, a series of metallated N‐confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL‐60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and effects on the cell cycle as well as the kinetics of proliferative activity of porphyrins and their respective metallated complexes in real time have been developed. The inhibitory activity of metallated porphyrins against human topoisomerase I and the possible mechanism of inhibition have been carried out by modelling using molecular docking. Clarity in confusion! We developed comparative in vitro studies of the topoisomerase I inhibitory and anticancer activities of metallated N‐confused porphyrins and metallated porphyrins. The synthetic porphyrins exhibit inhibitory activity against human topoisomerase I and high cytotoxic activity in vitro against K562, U937, HL‐60, Jurkat, A549 and HeLa cancer cell lines. Induction of programmed cell death in Jurkat cells by the metallated N‐confused porphyrin corresponds to the apoptotic pathway and has a predominant dose‐dependent effect on the S and G2 phases of the cell cycle.