Comparative Effects ofα-,β-, andγ-Carbolines on Platelet Aggregation and Lipid Membranes

Abstract

Cigarette smoking and alcohol consumption possibly affect platelet functions. To verify the hypothesis that some α-, β-, and γ-carboline components in cigarette smoke and alcoholic beverages may change platelet aggregability, their effects on human platelets were determined by aggregometry together with investigating their membrane effects by turbidimetry. Carbolines inhibited platelet aggregation induced by five agents with the potency being 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole > 3-amino-1-methyl-5H-pyrido[4,3-b]indole > 1-methyl-9H-pyrido[3,4-b]indole. The most potent 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole showed 50% aggregation-inhibitory concentrations of 6–172 μM. Both γ-carbolines interacted with phosphatidylcholine membranes to lower the lipid phase transition temperature with the potency correlating to the antiplatelet activity, suggesting that the interaction with platelet membranes to increase their fluidity underlies antiplatelet effects. Given their possible concentration and accumulation in platelets, γ- and β-carbolines would provide cigarette smokers and alcohol drinkers with reduced platelet aggregability, and they may be responsible for the occurrence of hemorrhagic diseases associated with heavy smoking and alcoholics.

Novel Glycoprotein VI Antagonists as Antithrombotics: Synthesis, Biological Evaluation, and Molecular Modeling Studies on 2,3-Disubstituted Tetrahydropyrido(3,4-b)indoles

“…The design of these molecules was based on the observed antiaggregatory effect of 3 S -1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid moiety present in plant A. chinense G. Don . There are ample evidence about β-carboline alkaloids preventing collagen-induced platelet aggregation. , Further the synthesized molecules reported by us have a tryptophan substructure in the β-carboline core that is reported to be essential for the binding of the peptide antagonist pep10L at the GPVI active site …”

Access to γ-Carbolines: Synthesis of Isocryptolepine

“… Carbolines are important structures for the development of biologically active molecules such as pharmaceuticals and materials. For instances, some carbolines exhibit anti-Alzheimer, BET bromodomain inhibitory, comparative effects on platelet aggregation and lipid, and anti-bovine viral diarrhea virus activities . Carbolines also exhibit photophysical properties and device performance based on high triplet energy host materials for deep blue devices .…”