harman and harmalol

Beta-carboline alkaloids present in Peganum harmala (harmal) have recently drawn attention due to their antitumor activities. The mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. They interact with DNA via both groove binding and intercalative modes and cause major DNA structural changes. The aim of this study was to examine the interactions of five beta-carboline alkaloids (harmine, harmane, harmaline, harmalol and tryptoline) with calf-thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various alkaloids/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 (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of alkaloids-DNA complexes in aqueous solution. Spectroscopic evidence showed major binding of alkaloids to DNA with overall binding constants of K(harmine)-DNA=3.44x10(7) M(-1), K(harmane)-DNA=1.63x10(5) M(-1), K(harmaline)-DNA=3.82x10(5) M(-1), K(harmalol)-DNA=6.43x10(5) M(-1) and K(tryptoline)-DNA=1.11x10(5) M(-1). The affinity of alkaloids-DNA binding is in the order of harmine>harmalol>harmaline>harmane>tryptoline. No biopolymer secondary structural changes were observed upon alkaloid interaction and DNA remains in the B-family structure in these complexes.

Topics: Animals; Antineoplastic Agents; Binding Sites; Carbolines; Cattle; DNA; Harmaline; Harmine; Intercalating Agents; Nucleic Acid Conformation; Peganum; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

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.

Topics: Carbolines; Harmaline; Harmine; Nucleic Acid Conformation; Peganum; Plants, Medicinal; RNA, Fungal

In the present study the antimicrobial potential of various extracts from 12 medicinal plants has been investigated in vitro on multiple antibiotic resistant pathogens and some selected protozoa isolated from poultry. The initial examination was performed on E. coli (n = 10) using disc and agar well diffusion assays. Only two plants, Peganum harmala (seeds) and Eucalyptus globulus (leaves) showed positive responses. The active extracts were also investigated against an additional 19 bacteria and the clonal cultures of three protozoa (Histomonas meleagridis, Tetratrichomonas gallinarum and Blastocystis sp.). Only Peganum harmala was found to inhibit the growth of all bacteria and protozoa at 0.38-1.55 mg/mL and 0.63-1.65 mg/mL, respectively. To investigate the potential role of alkaloids in crude extracts of Peganum harmala, four known beta-carbolin alkaloids were quantified and their antimicrobial activity was compared using a microdilution assay. Harmaline was found to be in the highest concentration followed by harmine and harmalol, whereas harmane could not be detected. The activity of the pure alkaloids was in the order harmane > harmaline > harmalol > or = harmine for all bacteria, while for protozoa, it was different depending on the microorganism. It is concluded that Peganum harmala or its alkaloids could probably be used for the control of antibiotic resistant isolates of bacteria as well as protozoa.

Topics: Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Bacteria; Carbolines; Chickens; Drug Resistance; Eukaryota; Harmaline; Harmine; Microbial Sensitivity Tests; Parasitic Sensitivity Tests; Peganum; Phytotherapy; Plant Extracts; Plants, Medicinal

Several microorganisms showed the ability to transform the harman alkaloids, harmaline (1), harmalol (2) and harman (5). Harmaline (1) and harmalol (2) were converted by Rhodotorula rubra ATCC 20129 into the tryptamines, 2-acetyl-3-(2-acetamidoethyl)-7-methoxyindole (3) and 2-acetyl-3-(2-acetamidoethyl)-7-hydroxyindole (4), respectively. Harman (5) was biotransformed by Cunninghamella echinulata NRRL 3655 into 6-hydroxyharman (6) and harman-2-oxide (7).

Topics: Biotransformation; Cunninghamella; Harmaline; Harmine; Magnetic Resonance Spectroscopy; Molecular Structure; Rhodotorula

Several beta-carboline (9H-pyrido-[3,4-b]-indole) alkaloids were evaluated for in vitro trypanosomicidal activity against Trypanosoma cruzi epimastigotes belonging to two different strains (Tulahuén and LQ) showing different sensitivity to nifurtimox. Important differences were observed in the susceptibility of the parasites to these natural substances, with the relatively nifurtimox-resistant LQ strain showing greater sensitivity to the beta-carbolines. Respiratory chain inhibition appears to be a possible determinant of the trypanosomicidal activity of these compounds.

Topics: Animals; Carbolines; Harmaline; Harmine; Kinetics; Nifurtimox; Oxygen Consumption; Species Specificity; Trypanocidal Agents; Trypanosoma cruzi

beta-Carboline alkaloids are derived as a result of condensation between indoleamine (e.g. tryptamine) and short-chain carboxylic acid (e.g. pyruvic acid) or aldehyde (e.g. acetaldehyde), a reaction that occurs readily at room temperature. These compounds have been found endogenously in human and animal tissues and may be formed as a byproduct of secondary metabolism: their endogenous functions however, are not well understood. Indoles and tryptophan derivatives exhibit antioxidative actions by scavenging free radicals and forming resonance stabilized indolyl radicals. Harmane and related compounds exhibited concentration-dependent inhibition of lipid peroxidation (measured as thiobarbiturate reactive products) in a hepatic microsomal preparation incubated with either enzymatic dependent (Fe3+ ADP/NADPH) or non-enzymatic dependent (Fe3+ ADP/dihydroxyfumarate) oxygen radical producing systems. Alkaloids with hydroxyl substitution and a partially desaturated pyridyl ring were found to have the highest antioxidative potencies. Substitution of a hydroxyl group by a methoxyl group at the 6-position resulted in a decrease of greater than 10-fold in the antioxidative activities. Harmane showed high efficacy in an enzymatic system but low efficacy in a non-enzymatic system. The antioxidative effects of harmane in the former system may be attributed to its ability to inhibit oxidative enzymes in the microsomal system. These results suggest that beta-carbolines may also serve as endogenous antioxidants.

Topics: Animals; Antioxidants; Carbolines; Dose-Response Relationship, Drug; Free Radicals; Harmaline; Harmine; Lipid Peroxidation; Male; Microsomes, Liver; Models, Chemical; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Thiobarbiturates; Tryptamines

The preparation of novel biologically active platinum(II) and palladium(II) complexes of some beta-carboline alkaloids (harmaline, harmalol, harmine, and harmane) is described. These complexes, characterized on the basis of their CHN elemental analysis, infrared, Raman and 1H and 13C nuclear resonance spectral data, were shown to have the empirical formula [M(alkaloid)Cl2], M = Pt, Pd. The antitumor and antiviral activities of some of these complexes have been demonstrated.

Topics: Alkaloids; Antineoplastic Agents; Antiviral Agents; Carbolines; Harmaline; Harmine; Magnetic Resonance Spectroscopy; Molecular Structure; Organometallic Compounds; Organoplatinum Compounds; Palladium; Spectrophotometry, Infrared; Spectrum Analysis, Raman; Tumor Cells, Cultured