Tag: 212.2472

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

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity was written by Poje, Goran;Marinovic, Marina;Pavic, Kristina;Mioc, Marija;Kralj, Marijeta;de Carvalho, Lais Pessanha;Held, Jana;Perkovic, Ivana;Rajic, Zrinka. And the article was included in International Journal of Molecular Sciences in 2022.Product Details of 442-51-3 This article mentions the following:

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biol. activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biol. assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle anal. revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell. In the experiment, the researchers used many compounds, for example, 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole (cas: 442-51-3Product Details of 442-51-3).

7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole (cas: 442-51-3) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Product Details of 442-51-3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles