DNA binding, antitumor activities, and hydroxyl radical scavenging properties of novel oxovanadium (IV) complexes with substituted isoniazid.
Four novel oxovanadium(IV) complexes—[VO(PAHN)(phen)] (1; PAHN is 4-pyridinecarboxylic acid, 2-[(2-hydroxy)-1-naphthalenylene] hydrazide, phen is 1,10-phenanthroline), [VO(PAHN)(bpy)] (2; bpy is 2,2′-bipyridine), [VO(PAH)(phen)] (3; PAH is 4-pyridinecarboxylic acid, 2-[(2-hydroxy)-1-phenyl]methylene hydrazide), and [VO(PAH)(bpy)] (4)—have been synthesized and characterized by elemental analysis, UV–vis spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy, 1H-NMR spectroscopy, and 13C-NMR spectroscopy. Their interactions with calf thymus DNA were investigated. The results suggest that these complexes bind to DNA in an intercalative mode. All four complexes exhibited highly cytotoxic activity against tumor cells (SH-SY5Y, MCF-7, and SK-N-SH), with 50 % inhibitory concentrations of the same order of magnitude as for cisplatin or of lower order of magnitude. Complex 1 exhibited the highest interaction ability and was found to be the most potent antitumor agent among the four complexes. It can cause G2/M phase arrest of the cell cycle, induces significant apoptosis in SK-N-SH cells, and displays typical morphological apoptotic characteristics. In addition, their hydroxyl radical scavenging properties have been tested, and complex 1 was the best inhibitor.
Xiangwen
X
Liao
Jiazheng
J
Lu
Peng
P
Ying
Ping
P
Zhao
Yinliang
Y
Bai
Wengjie
W
Li
Mingpei
M
Liu
D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D010618:Phenanthrolines; C075743:oxovanadium IV; D014638:Vanadates; D015082:2,2'-Dipyridyl; D004247:DNA; C427203:calf thymus DNA; D007538:Isoniazid; C025205:1,10-phenanthroline