Background: Toxoplasmosis is a worldwide infection caused by the protozoan parasite Toxoplasma gondii, which causes chorioretinitis and neurological defects in congenitally infected newborns or immunodeficient patients. The efficacy of the current treatment is limited, primarily by serious host toxicity. In recent years, research has focused on the development of new drugs against T. gondii. β-Carbolines (βCs), such as harmane, norharmane and harmine, are a group of naturally occurring alkaloids that show microbicidal activity. In this work, harmane, norharmane and harmine were tested against T. gondii. Findings: The treatment of extracellular tachyzoites with harmane, norharmane and harmine showed a 2.5 to 3.5-fold decrease in the invasion rates at doses of 40 μM (harmane and harmine) and 2.5 μM (norharmane) compared with the untreated parasites. Furthermore, an effect on the replication rate could also be observed with a decrease of 1 (harmane) and 2 (norharmane and harmine) division rounds at doses of 5 to 12.5 μM. In addition, the treated parasites presented either delayed or no monolayer lysis compared with the untreated parasites. Conclusions: The three βC alkaloids studied (norharmane, harmane and harmine) exhibit anti-T. gondii effects as evidenced by the partial inhibition of parasite invasion and replication. A dose–response effect was observed at a relatively low drug concentration (< 40 μM), at which no cytotoxic effect was observed on the host cell line (Vero).

β-Carbolines (βCs) are a group of alkaloids present in many plants and animals. It has been suggested that these alkaloids participate in a variety of significant photosensitized processes. Despite their well-established natural occurrence, the main biological role of these alkaloids and the mechanisms involved are, to date, poorly understood. In the present work, we examined the capability of three important βCs (norharmane, harmane and harmine) and two of its derivatives (N-methyl-norharmane and N-methyl-harmane) to induce DNA damage upon UV-A excitation, correlating the type and extent of the damage with the photophysical characteristics and DNA binding properties of the compounds. The results indicate that DNA damage is mostly mediated by a direct type-I photoreaction of the protonated βCs after non-intercalative electrostatic binding. Reactive oxygen species such as singlet oxygen and superoxide are not involved to a major extent, as indicated by the only small influence of D₂O and of superoxide dismutase on damage generation. An analysis with repair enzymes revealed that oxidative purine modifications such as 8-oxo-7,8-dihydroguanine, sites of base loss and single-strand breaks (SSB) are generated by all βCs, while only photoexcited harmine gives rise to the formation of cyclobutane pyrimidine dimers as well.

It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methyl-harmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet–triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D₂O, probably due to less rapid protonation in the deuterated solvent.