G-quadruplex DNA interactions, docking and cell photocytotoxicity research of porphyrin dyes. (May 2016)

• Record Type: Journal Article
• Authors: Zhao, Ping; Liu, Min-Chao; Zheng, Min; Jin, Shu-fang; Tang, Ding-tong; Chen, Jiong; Ma, Yan-na; Lin, Jia-qi; Wang, Xia-hong; Liu, Hong-jian
• Is Part Of: Dyes and pigments. Volume 128(2016)
• Page Start: 41
• Page End: 48
• Publication Date: 2016-05
• Subjects: Cationic porphyrins -- G-quadruplex DNA -- Spectral method -- Molecular dock -- Steric hindrance -- Photocytotoxicity; Dyes and dyeing -- Periodicals; Pigments -- Periodicals; 667.2
• DOI: 10.1016/j.dyepig.2016.01.009
• Languages: English
• ISSNs: 0143-7208

Abstract

Abstract: 5, 10, 15, 20-tetra-( N -methyl-2-pyridyl)porphyrin (TMPyP2 ) was always paid little attention because it has relatively low DNA-binding affinity and photocytotoxicity compared with its positional isomer 5, 10, 15, 20-tetra-( N -methyl-4-pyridyl)porphyrin (TMPyP4 ). Inspired by the previous successful results on higher bioactivities of ligands with larger aromatic surfaces, herein, 5, 10, 15, 20-tetra (phenyl-4-N-methyl-2-pyridyl) porphyrin (TPMPyP2 ), a TMPyP2 -like porphyrin with enlarged planar substituents, was designed and successfully synthesized. Results from spectral experiments and molecular docking calculation suggest that TPMPyP2 could partially overcome the steric hindrance of TMPyP2, with more favorable DNA-binding mode and lower molecular binding energy (M.B.E). Meanwhile, cell photocytotoxicity research indicates that TPMPyP2 shows higher antitumor potency than TMPyP2, which allowed the previous conclusion that the higher G-Quadruplexes DNA binding affinity would be related to better photocytotoxicity. Highlights: Novel expanded cationic porphyrin was successfully designed and synthesized. Spectral and Docking results show TPMPyP2 is more favorable in G4-DNA binding. TPMPyP2 is more potential as photochemotherapeutic agents.