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In a continuing effort to find new cytotoxic, antitumor, and less toxic agents from β-carbolines derivatives, using experimental and computational studies, five β-carboline alkaloids were tested in vitro for their cell growth inhibitory activity using Lepidium sativum phytotest. Then, molecular docking and correlation analysis between activity and structure study was performed to identify the interaction mode between these compounds and the colchicine binding site of tubulin. The experimental results revealed that harmaline and harmalol represent the most active compounds with IC50 of 134.15 μg/mL and 239.43 μg/mL, respectively, lower than colchicine which is 248 μg/mL. The correlation analysis between activity and structure indicates that the hydroxy group and the partial hydrogenation of the pyridyl ring increase activity. Indeed, molecular docking analysis revealed that harmaline and harmalol have low binding energy and could interact, in particular through conventional hydrogen bonds and van der Waals interactions with the colchicine binding site of tubulin, indicating that harmaline and harmalol could have an antimitotic effect. Moreover, in silico analysis of ADME/Tox properties reveals that these molecules possess promising pharmacokinetic properties in terms of intestinal adsorption, volume of distribution, blood-brain barrier permeability and toxicity. The results obtained were used to design new harmaline derivative molecule, with promising results after a preliminary in silico evaluation. In summary, our results indicate that the β-carboline alkaloids studied have an in vitro and in silico antimitotic activity and their pharmacokinetic properties are promising and should be confirmed by an in vivo study.

Background Diethylnitrosamine (DEN) promoted by carbon tetrachloride (CCl4) forms DNA adducts inducing hepatocellular carcinoma (HCC). Plant alkaloid, harmalol, is being used as a therapeutic agent against HCC due to its accessibility and efficacy by apoptosis and inhibiting proliferation of cancer epithelial cells. Result Seven groups of Swiss albino mice were taken. Different stages of liver tissues and serum from various experimental groups were collected before and after harmalol treatment. The investigation was carried out by enzyme assay, bilirubin level in the blood, DNA, RNA, normal serum protein of liver tissue, and alpha-feto protein estimation of serum. Gross morphological assessment of liver, histological, and different apoptosis markers viz. p53, caspase3, and cytochrome C expression were analyzed by RT-PCR and Western blot. Harmalol (10 mg/kg B.W. per week, I.P.) for 9 weeks showed a significant reduction in hepatocellular foci, nodules, and carcinoma ultimately retaining the normal morphology. It further induces ROS-dependent apoptosis through mitochondrial cytochrome C release that induces p53 by caspase3 activation. Conclusion The investigation will eventually help to develop more effective chemotherapeutic drugs from the natural source.

In order to find new, less toxic and eco-friendly pest control agents, natural products are considered to be alternative options of potentially active compounds. In this context, the aim of the present study was the isolation and structural elucidation of the β-carboline and quinazoline alkaloids of Peganum harmala L. seeds. Silver nanoparticles (AgNPs) were prepared using alkaloids through a green synthesis procedure. Harmala alkaloids and their AgNPs showed considerable insecticidal and growth inhibitory activities against khapra beetle, Trogoderma granarium (Everts) (Coleoptera: Dermestidae). On a toxicity bioassay using treated filter papers, the total harmala alkaloids (THAs) were the most toxic followed by harmaline, harmine and harmalol, where LC50’s ranged between (30.6–61.7 µg/cm2) and (24.4–46.1 µg/cm2) 24 h post-treatment against larvae and adults, respectively. The two quinazolines, vasicine and vasicinone, showed moderate to weak activities. At 48 h post-exposure, efficacy of all alkaloids was increased. When tested as AgNPs (size 22.5–66.2 nm diameter), toxicity of alkaloids, especially the β-carbolines, was strongly increased, where LC50 values ranged between (4.7–11.4 µg/cm2) and (4.1–10.2 µg/cm2) 48 h post-treatment against larvae and adults, respectively. Feeding the 2nd instar larvae AgNPs-treated grains at sublethal concentrations led to significant drawbacks on the normal growth and development of the insect. These effects appeared as a high percentage of malformed larvae and pupae, a prolonged life span and a significant reduction in adult emergence. Results suggest the potential of using harmala alkaloids and their AgNPs as a natural approach for controlling T. granarium.

Herbal remedies for human brain disorders are much preferred over synthetic drugs because of various side effects of synthetic drugs ranging from sleep disorders to withdrawal syndromes. Passiflora incarnata Linn (Passifloraceae) has been widely used in traditional medicine in West India, Mexico, the Netherlands, and South America. It has been used as an anxiolytic and sedative-hypnotic since ancient times. The main constituents of leaves of P. incarnata are flavonoid and indole alkaloids based on β -carboline ring system viz., harman, harmine, harmalol and harmaline. Harmine and harmaline alkaloids are reported to be effective antiparkinsonian compounds. The objective of present investigation was to evaluate antiparkinsonian activity and antioxidant activity of butanol extract of P. incarnata leaves (BEPI). Antiparkinsonian activity of BEPI was studied using haloperidol induced catalepsy and tacrine induced jaw movements. The antioxidant activity of BEPI was studied using DPPH scavenging assay and H2O2 scavenging assay. The results of present study has shown that butanol extract of P. incarnata leaves (BEPI) (150 mg kg−1 and 300 mg kg−1, i.p.) significantly (p ≤ 0.001) reduced the duration of haloperidol induced catalepsy as well as tacrine induced jaw movements. BEPI has also shown significant antioxidant effect. The result obtained in current study indicates that BEPI posses antiparkinsonian as well as antioxidant activity which may be useful in symptomatic relief of PD and to prevent progression of PD.

Room temperature electronic absorption and fluorescence spectra of harmol, harmalol and 2-hydroxycarbazole have been obtained in concentrated aqueous potassium hydroxide solutions. The appearance of a new fluorescence band for all these compounds in media of H- greater than 16, has been ascribed to the emission of excited dianions formed by deprotonation. Acidity constants have been estimated from the Föster-Weller method.

Platinum(II) and palladium(II) complexes of general formulatrans-[MCl2LL] (M=Pt or Pd, L, L′=β-carboline; M=Pt, L=β-carboline, L′=ethene; β-carboline alkaloids are harmaline, harmine, harmalol as hydrochloride derivatives) have been prepared for the first time. The structures were assigned and identified on the basis of their CHN analyses, i.r. and1H n.m.r. spectra. The decomposition products of these complexes in DMSO have been described.