Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

Olmo, Esther del; Barboza, Bianca; Chiaradia, Louise Domeneghini; Moreno, Angel J.; Carrero-Lérida, Juana; González-Pacanowska, Dolores; Muñoz, Verónica Francisca Loewe; López-Pérez, Jose Luis; Giménez, Alberto; Benito, Agustín; Martínez, Antonio; Ruíz-Pérez, Luis M.; Feliciano, Arturo San

doi:10.1016/j.ejmech.2011.08.043

Cited by 19 publications

(19 citation statements)

References 19 publications

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“…In addition, 1,2,3-triazole-tethered ␤-lactam and 7-chloroquinoline bifunctional hybrids were synthesized and showed reasonable antimalarial activities, with IC 50 values ranging from 1. (24,25). A series of novel ketoenamine chalcone-chloroquine-based hybrids were synthesized, and compounds 25 and 27 each showed 99.9% in vivo suppression of parasitemia at a dosage of 100 mg/ kg/day by the oral route (26).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Zhao

et al. 2014

Antimicrob Agents Chemother

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dArtemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation. Malaria is one of the most significant causes of morbidity and death worldwide. Every year, nearly one million deaths result from malaria infection, with about 85% occurring among children under 5 years of age. Indeed, one patient dies from malaria every 36 s (1).Artemisinin and its derivatives are the most important antimalarial drugs; the chemical structures of the four artemisinin compounds and lumefantrine (also known as benflumetol) are presented in Fig. 1. Artemisinin is an effective antimalarial drug isolated from the Chinese herbal medicine Artemisia annua L. It has a special sesquiterpene lactone with a peroxy group. In malaria parasites, artemisinin can be activated by intraparasitic heme iron, which catalyzes cleavage of the endoperoxide (2). Due to its unique structure and antimalarial mechanism, artemisinin has excellent antimalarial activity with low toxicity; therefore, artemisinin-based combination therapy (ACT) is recommended as the first-line strategy to treat malaria (3). After the introduction of ACT interventions, morbidity and mortality rates associated with malaria were decreased in several parts of the world (4). However, antimalarial resistance would probably be increased after longterm application of artemisinin alone. WHO reformed the malaria treatment policy in February 2004, proposing to stop the use of single antimalarial drugs (e.g., artemisinin and quinine) and promoting the use of ACTs. Recently, combination therapies such as artemether in co...

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Section: Discussionmentioning

confidence: 99%

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Zhao

et al. 2014

Antimicrob Agents Chemother

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“…Recently, it was described that the synthesis of a series of thiazolidinones (52) (Fig. falciparum F32 and 3D7 strains, with IC 50 values of about 0.05 mM [75,76]. Heterocyclic synthetic compounds sharing in common the presence of a natural carbonated dihydrostilbene fragment, such as imidazo[2,1-a]isoindololes (53-56) (Fig.…”

Section: Malariamentioning

confidence: 99%

“…falciparum [70,71] Allicin (50) IC 50 -5.21 mM Inhibition of falcipain [72] Myricetin (51) IC 50 -0.4 mM Inhibition of Fabl [73] (Continued) Imidazo [1,2] isoindolole (53) IC 50 -0.04 mM Pl. falciparum chloroquinesensitive (F32) [75,76] Imidazo [2,1-a] isoindolole (54) IC 50 --0.07 mM Pl. falciparum chloroquinesensitive (F32) [75,76] Imidazo [2,1-a] isoindolole (55) IC 50 -0.06 mM Pl.…”

Section: Introductionmentioning

confidence: 99%

“…falciparum chloroquinesensitive (F32) [75,76] Imidazo [2,1-a] isoindolole (54) IC 50 --0.07 mM Pl. falciparum chloroquinesensitive (F32) [75,76] Imidazo [2,1-a] isoindolole (55) IC 50 -0.06 mM Pl. falciparum chloroquinesensitive (3D7) [75,76] Imidazo [1,2] Isoindolole (56) IC 50 -0.06 mM Pl.…”

Section: Introductionmentioning

confidence: 99%

“…falciparum chloroquinesensitive (3D7) [75,76] Imidazo [1,2] Isoindolole (56) IC 50 -0.06 mM Pl. falciparum chloroquinesensitive (3D7) [75,76] Chagas Disease Polygodial (57) IC 50 -2.03 mg/mL T. cruzi trypromastigotes [80] Semisynthetic chromene (58) IC 50 -2.8 mM T. cruzi epimastigotes [81] Chromene (59) IC 50 -3.1 mM T. cruzi epimastigotes [82] Polyacetylene (60) IC 50 -0.40 mM T. cruzi amastigotes [83] Gigantetrocin (61) IC 50 -0.019 mg/mL T. cruzi trypromastigotes [84] Quinine (62) IC 50 -14 mM T. cruzi epimastigotes [85] Quinidine (63) IC 50 -14 mM T. cruzi epimastigotes [85] Cinchonidine (64) IC 50 -14 mM T. cruzi epimastigotes [85] Cinchonine (65) IC 50 -14 mM T. cruzi epimastigotes [85] Duguetine (66) IC 50 -9.32 mM T. cruzi trypomastigotes [86] [87][88][89] IC 50 -0.67 mM T. cruzi epimastigotes [87][88][89] Eupomatenoid-5 (69) IC 50 -7.0 mg/mL T. cruzi epimastigotes [90] Eupomatenoid-6 (70) IC 50 -7.5 mg/mL T. cruzi epimastigotes [90] Conocarpan (71) IC 50 -8.0 mg/mL T. cruzi epimastigotes [90] Lupeol (72) IC 50 -40.8 mg/mL Inhibition of cruzain [94] Chalcones (73)(74)(75) IC 50 -20 mM Inhibition of cruzain [98] Human African Trypanosomiasis 4'-Hydroxy-5,6,7,3',5'pentamethoxyflavone IC 50 -7.8 mM T. b. rhodesiense [104]…”

Section: Introductionmentioning

confidence: 99%

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From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)

Oliveira

Chiaradia-Delatorre²,

Mascarello³

et al. 2015

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Imidazo‐Fused Isoindoles by Pd(II)/Ag(I)‐Promoted Intramolecular Dehydrogenative Coupling

et al. 2020

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An effective Pd(II)/Ag(I)‐promoted intramolecular cross‐dehydrogenative coupling (CDC) of substituted 1‐benzylimidazoles under air provides, for the first time, a simple access to several functionalized imidazo[2,1‐a]isoindoles, an interesting class of polycyclic heteroaromatic compounds. The direct involvement of two unactivated carbon–hydrogen bonds, without any directing group, grants an elevated atom economy of the whole process.

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Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

Cited by 19 publications

References 19 publications

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)

Imidazo‐Fused Isoindoles by Pd(II)/Ag(I)‐Promoted Intramolecular Dehydrogenative Coupling

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