N-[2(3-Carboxyl-9-benzyl-carboline-1-yl)ethyl-1-yl]-amino acids: correlation of spectral property with in vivo anti-tumor activity

Abstract

To clarify the relationships of the commonly used spectral measurements and the in vivo activity of b-carboline intercalators N-[2(3-carboxyl-9-benzyl-carboline-1-yl)ethyl-1-yl]-aspartic acid (3a), -tyrosine (3b), -serine (3c), and -threonine (3d) were prepared as the model compounds by using a three-step procedure. In UV measurements of calf thymus DNA (CT DNA) the in vivo active 3a-c induced both hypochromic effect and hypsochromic shift, while the in vivo inactive 3d did not. In CD measurements the in vivo active 3a-c changed the intensities of both positive and negative bands of CT DNA in same direction, while the in vivo inactive 3d induced an opposite change. In fluorescence measurements due to adding CT DNA the increase of the fluorescence intensities of 3a-c were 10-31% higher than that of 3d, and the bathochromic shifts of 3a-c were 2-6 nm higher than that of 3d. The viscositic experiments revealed that 3d possessed the lowest binding ratio. The melting curves indicate that the effect of 3a-c (DT m , 10.8-12.9°C) on the T m of CT DNA was significantly higher than that of 3d (DT m , 4.9°C). Spectroscopic, viscositic, and melting curve investigations are not only able to provide multiple evidences for DNA intercalation mechanism, but also are able to distinguish the in vivo active and inactive N-[2(3-carboxyl-9-benzyl-carboline-1-yl)-ethyl-1-yl]-amino acids.

<em>N</em>-(3-hydroxymethyl-&beta;-carboline-1-yl-ethyl-2-yl)-L-Phe: development toward a nanoscaled antitumor drug capable of treating complicated thrombosis and inflammation

“…Structural similarity of intercalators N -[2(3-carboxyl-9-benzyl/H-carboline-1-yl)ethyl-1-yl]-amino acids,24–27 benzyl1-(4-hydroxy-3-methoxycarbonyl-phenyl)-9H-pyrido[3,4-b] indole-3-carboxylate (BPIC),28 N -[1-(3-methoxycarbonyl-4-hydroxyphenyl)-β-carboline-3-carbonyl]-Trp-Lys-OBzl (PZL318)29 and benzyl N ω -nitro- N α -(9H-pyrido[3,4-b]indole-3-carbonyl)-L-argininate (NRCB)30 with HMCEF means that HMCEF may be an intercalator (Figure 1). …”

Developing a Novel Indolocarbazole as Histone Deacetylases Inhibitor against Leukemia Cell Lines

“…Indole alkaloids constitute a group of natural products that have attracted great attention as anticancer leading compounds [ 18 , 19 ]. As a unique class of indole alkaloids, indolocarbazoles had been reported with an array of interesting biological activities [ 20 ].…”

Synthesis and Preliminary Study on the DNA-binding Property of Tranexamic Acid Derivatives

“…The final derivatives were isolated with high purity (>95%) and characterized via 1 H-NMR and ESI-MS. The characterization results of TA derivatives are as follows: When small molecules interact with the DNA, the contraction and extension of the DNA molecule usually induces hypochromicity in UV spectra of the interaction system, and the explosion of DNA base pair lead hyperchromicity [10][11][12] . Ultraviolet absorption at 260 nm of ctDNA showed a hypochromic effect with increasing concentration of TA and derivatives and the maximum absorption wavelength remained unchanged.…”