{2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (MIAM): its anti-cancer efficacy and intercalation mechanism identified via multi-model systems.
{2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (MIAM) was provided as a DNA-intercalator. For the comprehensive evaluation of this new intercalator, an assay system consisting of cell, S180 mouse, healthy mouse, spectrum, non-spectrum, and gel electrophoresis models was constructed. On the cell (S180, K562, MCF-7, HeLa and HepG2) models, MIAM selectively inhibited the viability of HeLa. On the S180 mouse model, 0.89, 8.9, 89 and 890 μmol kg(-1) of MIAM dose-dependently inhibited the tumor growth. Even at a dose of 890 μmol kg(-1), MIAM did not damage the treated S180 mice. The safety of MIAM was supported by a high spleen index and an obvious increase of body weight of the treated S180 mice. On the healthy mouse model the LD(50) value of MIAM is higher than 890 μmol kg(-1). The ultraviolet (UV), fluorescence, circular dichroism (CD), relative viscosity, melting curve, and gel electrophoresis assays of DNA with or without MIAM consistently supported an intercalation mechanism for MIAM.
College of Pharmaceutical Sciences, Capital Medical University, Beijing 1000, 69, P.R. China.
Wenjing
W
Wang
Ming
M
Zhao
Yuji
Y
Wang
Jiawang
J
Liu
Jianhui
J
Wu
Guifeng
G
Kang
Shiqi
S
Peng
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007210:Indoleacetic Acids / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology
C559930:(2-(1-(3-methoxycarbonylmethyl-1H-indol-2-yl)-1-methylethyl)-1H-indol-3-yl)acetic acid methyl ester; D000970:Antineoplastic Agents; D007210:Indoleacetic Acids; D004247:DNA; C427203:calf thymus DNA