Antileishmanial activity of a new 8-hydroxyquinoline derivative designed 7-[5′-(3′-phenylisoxazolino)methyl]-8-hydroxyquinoline: preliminary study

Dardari, Zainaba; Lemrani, Meryem; Bahloul, Abdelmejid; Sebban, Abdelfatah; Hassar, Mohammed; Kitane, S.; Berrada, Mohamed Saleh; Boudouma, Mohammed

doi:10.1016/j.farmac.2003.11.001

Cited by 47 publications

(19 citation statements)

References 17 publications

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“…Promastigote drug susceptibility determinations were made using a previously described direct counting assay based on growth inhibition [42]. Promastigotes were seeded at an initial concentration equivalent to 1.5610 6 promastigote/mL and allowed to multiply for 8 days in medium alone or in the presence of serial dilutions of the drug ranging from 0.05 to 10 lg/ mL.…”

Section: Promastigote Drug Susceptibility Assaymentioning

confidence: 99%

Antileishmanial and Antibacterial Activity of a New Pyrazole Derivative Designated 4‐[2‐(1‐(Ethylamino)‐2‐methyl‐ propyl)phenyl]‐3‐(4‐methyphenyl)‐1‐phenylpyrazole

Dardari

Lemrani

Sebban

et al. 2006

Archiv der Pharmazie

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Here, we report for the first time the synthesis and the antileishmanial activity of a new pyrazole derivative, namely 4-[2-(1-(ethylamino)-2-methylpropyl)phenyl]-3-(4-methyphenyl)-1-phenylpyrazole). Micromolar concentrations of this compound were found to inhibit the in vitro multiplication of Leishmania tropica, Leishmania major, and Leishmania infantum, three species causing different forms of leishmaniasis. Furthermore, the 50% inhibitory concentration (IC50) values for the compound are only slightly higher than those of amphotericin B, one of the most active antileishmanial agents used as a satisfactory substitute in cases not responding to pentostam. The IC50 values after 48 h for L. tropica, L. major, and L. infantum promastigote growth were 0.48 microg/mL, 0.63 microg/mL and 0.40 microg/mL, respectively for the compound, while they were 0.23 microg/mL, 0.29 microg/mL and 0.24 microg/mL, respectively for amphotericin B. We also tested this compound for its antibacterial activity against several bacteria. The strongest antibacterial activity was observed against Entrococcus feacalis and Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 60 microg/mL.

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Section: Promastigote Drug Susceptibility Assaymentioning

confidence: 99%

Antileishmanial and Antibacterial Activity of a New Pyrazole Derivative Designated 4‐[2‐(1‐(Ethylamino)‐2‐methyl‐ propyl)phenyl]‐3‐(4‐methyphenyl)‐1‐phenylpyrazole

Dardari

Lemrani

Sebban

et al. 2006

Archiv der Pharmazie

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“…Indeed, 8-HQN and its derivates have been reported to possess antitumor (Collery et al 2000;Tzeng et al 2000) and antimicrobial (Lentz et al 1999;Shen et al 1999) activities, as well as been evaluated as a candidate for the treatment of HIV-infected patients, cancer, neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, and to treat against parasitic and bacterial infections (Lentz et al 1999;Prachayasittikul et al 2013). In leishmaniasis, previous studies have shown that 8-HQN inhibits the growth of L. infantum, L. panamensis, L. tropica, and L. major promastigotes (Dardari et al 2004;Fuertes et al 2008). A recent study developed by our group described the antileishmanial activity of 8-HQN against in vitro stationary promastigotes and in vivo intra-macrophage amastigotes of three different Leishmania species, L. amazonensis, L. braziliensis, and L. infantum.…”

Section: Introductionmentioning

confidence: 96%

An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis

et al. 2016

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The current treatment of leishmaniasis has been hampered due to the high toxicity of the available drugs and long duration protocols, which often lead to its abandonment. In the present study, a poloxamer 407-based delivery system was developed, and a molecule, 8-hydroxyquinoline (8-HQN), was incorporated with it, leading to an 8-HQN/micelle (8-HQN/M) composition. Assays were performed to evaluate the in vitro antileishmanial activity of 8-HQN/M against Leishmania amazonensis stationary promastigotes. The cytotoxicity in murine macrophages and in human red cells, as well as the efficacy of the treatment in macrophages infected by parasites, was also assessed. This product was also evaluated for the treatment of murine tegumentary leishmaniasis, using L. amazonensis-infected BALB/c mice. To evaluate the in vivo efficacy of the treatment, the average lesion diameter (area) in the infected tissue, as well as the parasite load at the site of infection (skin), spleen, liver and draining lymph nodes were examined. Non-incorporated micelle (B-8-HQN/M) and the free molecule (8-HQN) were used as controls, besides animals that received only saline. The parasite burden was evaluated by limiting dilution and quantitative real-time PCR (qPCR) techniques, and immunological parameters associated with the treatments were also investigated. In the results, the 8-HQN/M group, when compared to the others, presented more significant reductions in the average lesion diameter and in the parasite burden in the skin and all evaluated organs. These animals also showed significantly higher levels of parasite-specific IFN-γ, IL-12, and GM-CSF, associated with low levels of IL-4 and IL-10, when compared to the saline, 8-HQN/M, and B-8-HQN groups. A predominant IL-12-driven IFN-γ production, against parasite proteins, mainly produced by CD4 T cells, was observed in the treated animals, post-infection. In conclusion, 8-HQN/M was highly effective in treating L. amazonensis-infected BALB/c mice and can be considered alone, or combined with other drugs, as an alternative treatment for tegumentary leishmaniasis. Graphical Abstract Therapeutic scheme and immunological and parasitological parameters developed in the present study.

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“…An 8-hydroxyquinoline derivative containing aminobenzothiazole is also known to inhibit dengue virus type 2 protease in vitro (Lai et al 2013). Furthermore, a new synthetic 8-hydroxyquinoline derivative, namely 7-[5′-(3′-phenylisoxazolino)methyl]-8-hydroxyquinoline, was found to inhibit growth of Leishmania tropica, Leishmania major, and Leishmania infantum at micromolar concentrations (Dardari et al 2004). Despite its inhibitory effects against cancer cells, viruses, and various Leishmania species, its interaction with target pathogen proteins or drug transport proteins, such as serum albumen, is not recognized.…”

Section: Introductionmentioning

confidence: 98%

Effects of 2-amino-8-hydroxyquinoline interaction on the conformation of physiological isomers of human serum albumin

et al. 2015

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The methods of synthetic chemistry create small molecules rapidly for screening, and ligand-protein interaction studies provide information on how a potential drug interacts with target or carrier proteins such as serum albumin. In this work, we investigate the interaction of amino derivative of 8-hydroxyquinoline, 2-amino-8-hydroxyquinoline (A8HQ), and the effects of its binding on the conformation of different isomers of human serum albumin (HSA) using multispectroscopic techniques and molecular modeling. We found that B isomer, which exists at pH 9, bound A8HQ (K a = 1.92 ± 0.07 × 10(5) M(-1) at 298 K) more strongly as compared with N isomer (K a = 1.19 ± 0.04 × 10(5) M(-1) at 298 K) of HSA, which is known to exist around pH 6. The binding constant at physiological pH (7.4) was also determined, and the value (K a = 1.38 ± 0.05 × 10(5) M(-1) at 298 K) was found to fall between those for N and B isomers, suggesting that both the N and B isomers exist in an equilibrium in plasma. We also determined the thermodynamic parameters such as changes in enthalpy, entropy , and free energy of binding by measuring the binding at four different temperatures. Based on molecular modeling and thermodynamic studies, we propound that the A8HQ-HSA binding involves mainly hydrophobic interactions and hydrogen bonding. Site-specific marker displacement experiments and molecular modeling showed that the molecule preferably binds in subdomain IIA close to Trp214. A8HQ binding to HSA isomers was found to cause both secondary and tertiary structural alterations in the protein.

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Antileishmanial activity of a new 8-hydroxyquinoline derivative designed 7-[5′-(3′-phenylisoxazolino)methyl]-8-hydroxyquinoline: preliminary study

Cited by 47 publications

References 17 publications

Antileishmanial and Antibacterial Activity of a New Pyrazole Derivative Designated 4‐[2‐(1‐(Ethylamino)‐2‐methyl‐ propyl)phenyl]‐3‐(4‐methyphenyl)‐1‐phenylpyrazole

Antileishmanial and Antibacterial Activity of a New Pyrazole Derivative Designated 4‐[2‐(1‐(Ethylamino)‐2‐methyl‐ propyl)phenyl]‐3‐(4‐methyphenyl)‐1‐phenylpyrazole

An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis

Effects of 2-amino-8-hydroxyquinoline interaction on the conformation of physiological isomers of human serum albumin

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