Synthesis of Benzocycloalkanone-Based Michael Acceptors and Biological Activities as Antimalarial and Antitrypanosomal Agents

Mijoba, Ali; Fernandez-Moreira, Esteban; Parra-Giménez, Nereida; Espinosa-Tapia, Sandra; Blanco, Zuleyma; Ramírez, Hegira; Charris, Jaime E.

doi:10.3390/molecules28145569

Cited by 2 publications

(3 citation statements)

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“…Solubilizing the aggregates with NaOH (0.1 N) further allowed us to measure their absorbance at 405 nm (BIORAD-550 microplate reader) (BIO-RAD Laboratories, Hercules, CA, USA). The outcomes are expressed as percentages of inhibition of β-H formation [60].…”

Section: Inhibition Of β-Hematin Formationmentioning

confidence: 99%

“…The animals were infected with the rodent malaria ANKA strain of Plasmodium berghei; 1 × 10 6 infected erythrocytes diluted in phosphate-buffered saline (PBS; 10 mM, pH 7.4, 0.1 mL) were injected intraperitoneally into mice. Microscopic examination of Giemsastained smears was used to monitor parasitaemia [20,60].…”

Section: Parasite Experimental Host and Strain Maintenancementioning

confidence: 99%

“…A control group of mice infected with P. berghei incubated with saline solution was used to determine survival times. The results are expressed as a percentage of parasitaemia, and the survival curve was constructed based on the number of days of survival after treatment with the compound over that of mice infected without treatment [20,60,61].…”

Section: Four-day Suppressive Testmentioning

confidence: 99%

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Synthesis, Antimalarial, Antileishmanial, and Cytotoxicity Activities and Preliminary In Silico ADMET Studies of 2-(7-Chloroquinolin-4-ylamino)ethyl Benzoate Derivatives

Gutiérrez,

Ramírez,

Fernandez-Moreira

et al. 2023

Pharmaceuticals

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A series of heterocyclic chloroquine hybrids, containing a chain of two carbon atoms at position four of the quinolinic chain and acting as a link between quinoline and several benzoyl groups, is synthesized and screened in vitro as an inhibitor of β-hematin formation and in vivo for its antimalarial activity against chloroquine-sensitive strains of Plasmodium berghei ANKA in this study. The compounds significantly reduced haeme crystallization, with IC50 values < 10 µM. The values were comparable to chloroquine’s, with an IC50 of 1.50 ± 0.01 µM. The compounds 4c and 4e prolonged the average survival time of the infected mice to 16.7 ± 2.16 and 14.4 ± 1.20 days, respectively. We also studied the effect of the compounds 4b, 4c, and 4e on another important human parasite, Leishmania mexicana, which is responsible for cutaneous leishmaniasis, demonstrating a potential leishmanicidal effect against promasigotes, with an IC50 < 10 µM. Concerning the possible mechanism of action of these compounds on Lesihmania mexicana, we performed experiments demonstrating that these three compounds could induce the collapse of the parasite mitochondrial electrochemical membrane potential (Δφ). The in vitro cytotoxicity assays against mammalian cancerous and noncancerous human cell lines showed that the studied compounds exhibit low cytotoxic effects. The ADME/Tox analysis predicted moderate lipophilicity values, low unbound fraction values, and a poor distribution for these compounds. Therefore, moderate bioavailability was expected. We calculated other molecular descriptors, such as the topological polar surface area, according to Veber’s rules, and except for 2 and 4i, the rest of the compounds violated this descriptor, demonstrating the low antimalarial activity of our compounds in vivo.

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Section: Inhibition Of β-Hematin Formationmentioning

confidence: 99%

Section: Parasite Experimental Host and Strain Maintenancementioning

confidence: 99%