Synthesis and Evaluation of β-Carbolinium Cations as New Antimalarial Agents Based on π-Delocalized Lipophilic Cation (DLC) Hypothesis

Abstract

Several b b-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral b b-carbolines and a good correlation was observed between p p-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. b b-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

Total synthesis of cordatanine, structural reassignment of drymaritin, and anti-inflammatory activity of synthetic precursors

“…Therefore, we decided to follow the procedure of Takasu et al and adapt a Pictet-Spengler reaction for ring closure (Scheme 1). 4 Tryptamine was used as starting material and underwent a Pictet-Spengler reaction with ethyl glyoxylate followed by direct oxidative aromatization catalyzed with Pd/C to give kumujian A (3) (42%). Aldol condensation using sodium bis(trimethylsilyl)amide (NaHMDS) and ethyl acetate (EA) produced an acetate carbanion, which reacted with 3 to give 4. result a tautomeric enolate anion.…”

From green chemistry to nature: The versatile role of low transition temperature mixtures

“…The mechanism explaining the damaging effect of DES on microorganisms may be associated to their interactions with the cellular membranes. This greater DES 0 anti-bacterial activity compare to that of their individual constituents, may be attributed to the charge delocalization through the hydrogenbonding between the anion and the HBD, a mechanism similar to the antimicrobial activity of well-observed Delocalized Lipophilic Cations (DLC) [26,27].…”

π-Delocalized Lipophilic Cations as New Candidates for Antimalarial, Antitrypanosomal and Antileishmanial Agents: Synthesis, Evaluation of Antiprotozoal Potency, and Insight into Their Action Mechanisms

“…Improvements in the Antimalarial Activities of the Natural Alkaloids Using the DLC Hypothesis 35,36) The β-carboline alkaloids are widely found in a number of plants. Some of these alkaloids exhibit a variety of biological and pharmaceutical potencies including antimalarial activity [37][38][39][40] (Fig.…”

“…This study demonstrated that the transformation into a DLC structure could prove to be a highly effective modified method for preparing and designing antimalarial compounds. 35,36) …”

“…The uptake of the rhodacyanines in mitochondria may play a key role in inhibiting malaria diseases. 36,[56][57][58][59][60][61] The causal pathogenic parasites of NTDs, such as Trypanosoma spp. and Leishmania spp., belong to the Trypanosomatidae family in the Euglenozoa phylum.…”