Interaction of β-carboline alkaloids with RNA.
β-Carboline alkaloids are present in medicinal plants such as Peganum harmala L., which have been used as folk medicine in anticancer therapy. Recently, they have drawn attention because of their antitumor activities. Despite considerable interest and investigations on alkaloid-DNA complexes, reports on alkaloid-RNA interaction are very limited. This study is the first attempt to investigate the binding of β-carboline alkaloids (harmine, harmane, harmaline, harmalol, and tryptoline) with yeast RNA. The effect of alkaloid complexation on RNA aggregation and condensation was investigated in aqueous solution at physiological conditions, using constant RNA concentration (6.25 mM) and various alkaloid:polynucleotide (phosphate) ratios of 1:240, 1:160, 1:80, 1:40, 1:20, 1:10, 1:5, 1:2, and 1:1. Fourier transform infrared and UV-visible spectroscopic methods were used to determine the ligand-binding modes, the binding constants, and the stability of alkaloid-RNA complexes in aqueous solution. Spectroscopic evidence showed major binding of alkaloids to RNA with overall binding constants of K(harmine)-RNA = 2.95 × 10⁷ M⁻¹, K(harmane)-RNA = 5.62 × 10⁵ M⁻¹, K(harmaline)-RNA = 7.47 × 10⁵ M⁻¹, K(harmalol)-RNA = 4.32 × 10⁵ M⁻¹, and K(tryptoline)-RNA = 3.21 × 10⁵ M⁻¹. The affinity of alkaloids-RNA binding is in the order of harmine > harmaline > harmane > harmalol > tryptoline. No biopolymer secondary structural changes were observed upon alkaloid interaction and RNA remains in the A-family structure in these complexes.
Nafisi
Shohreh
S
Department of Chemistry, Azad University, Tehran, Iran. s.nafisi@neu.edu
Malekabady
Zahra Mokhtari
ZM
Khalilzadeh
Mohammad Ali
MA
D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology; D006246:Harmaline / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D032443:Peganum / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D012331:RNA, Fungal / Q000737:chemistry* / Q000187:drug effects
D002243:Carbolines; D012331:RNA, Fungal; C007904:harmalol; D006247:Harmine; C009804:tryptoline; C005010:harman; D006246:Harmaline