Quadruplex-Interactive Agents as Telomerase Inhibitors:  Synthesis of Porphyrins and Structure−Activity Relationship for the Inhibition of Telomerase

• Published in: Journal of medicinal chemistry Vol. 44; no. 26; pp. 4509 - 4523
• Main Authors: Shi, Dong-Fang, Wheelhouse, Richard T, Sun, Daekyu, Hurley, Laurence H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.12.2001; Amer Chemical Soc
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell-Free System; Chemistry, Medicinal; DNA - chemistry; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; G-Quadruplexes; General aspects; HeLa Cells; Humans; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Porphyrins - chemical synthesis; Porphyrins - chemistry; Porphyrins - pharmacology; Pyridines - chemistry; Pyrroles - chemistry; Science & Technology; Structure-Activity Relationship; Telomerase - antagonists & inhibitors; PYRROLIC COMPOUNDS; TARGET; CATIONIC PORPHYRINS; FRAGILITY; DNA; CHEMISTRY; SEPARATION; IDENTIFICATION; BINDING; DERIVATIVES; Antineoplastic agent; Pentacyclic compound; Human; Organic cation; Enzyme; Nitrogen heterocycle; Iminium compounds; Benzene derivatives; Enzyme inhibitor; Molecular interaction; In vitro; Modeling; Telomere; Tetrad; Macrocycle; Pyridine derivatives; Biological fixation; Structure activity relation; Molecular model; Aromatic compound; Mechanism of action; Chemical synthesis; Telomerase

The cationic porphyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4) binds to quadruplex DNA and is thereby an inhibitor of human telomerase (Wheelhouse et al. J. Am. Chem. Soc. 1998, 120, 3261−3262). Herein the synthesis and telomerase-inhibiting activity of a wide range of analogues of T...