Design and synthesis of harmiquins, harmine and chloroquine hybrids as potent antiplasmodial agents was written by Poje, Goran;Pessanha de Carvalho, Lais;Held, Jana;Moita, Diana;Prudencio, Miguel;Perkovic, Ivana;Tandaric, Tana;Vianello, Robert;Rajic, Zrinka. And the article was included in European Journal of Medicinal Chemistry in 2022.Application In Synthesis of 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole This article mentions the following:
Malaria remains one of the major health problems worldwide. The lack of an effective vaccine and the increasing resistance of Plasmodium to the approved antimalarial drugs demands the development of novel antiplasmodial agents that can effectively prevent and/or treat this disease. Harmiquins represent hybrids that combine two moieties with different mechanisms of antiplasmodial activity in one mol., i.e., a chloroquine (CQ) scaffold, known to inhibit heme polymerization and a β-carboline ring capable of binding to P. falciparum heat shock protein 90 (PfHsp90). Here we present their synthesis, evaluation of biol. activity and potential mechanism of action. The synthesized hybrids differed in the type of linker employed (triazole ring or amide bond) and in the position of the substitution on the β-carboline core of harmine. The antiplasmodial activity of harmiquins was evaluated against the erythrocytic stage of the Plasmodium life cycle, and their cytotoxic effect was tested on HepG2 cells. The results showed that harmiquins exerted remarkable activity against both CQ-sensitive (Pf3D7) and CQ-resistant (PfDd2, PfK1, and Pf7G8). P. falciparum strains. The most active compound, I, displayed single-digit nanomolar IC50 value against Pf3D7 (IC50 = 2.0 ± 0.3 nM). Importantly, it also showed significantly higher activity than CQ against the resistant Plasmodium strains and had a very high selectivity index (4450). Harmiquins may act through the inhibition of heme polymerization and binding to the ATP binding site of the PfHsp90, which would explain their increased activity against the CQ-resistant Plasmodium strains. These results establish harmiquins as valuable antiplasmodial hits for future optimization. In the experiment, the researchers used many compounds, for example, 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole (cas: 442-51-3Application In Synthesis of 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole).
7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole (cas: 442-51-3) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Application In Synthesis of 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole
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Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles