Synergistic anti-malarial action of cryptolepine and artemisinins

Forkuo, Arnold Donkor; Ansah, Charles; Boadu, Kwesi M.; Boampong, Johnson Nyarko; Ameyaw, Elvis Ofori; Gyan, Ben; Arku, Andrea Twumwaa; Ofori, Michael F.

doi:10.1186/s12936-016-1137-5

Cited by 27 publications

(27 citation statements)

References 30 publications

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“…The FIC 50 s for each fixed dose ratio were calculated from the individual EC 50 values obtained from the dose-response curves (55). The sum of the FIC 50 s (⌺FIC 50 s) was represented as isobolograms calculated using the following equation: ⌺FIC 50 ϭ (EC 50 of salinomycin in combination/EC 50 of salinomycin alone) ϩ (EC 50 of OSV-C in combination/EC 50 of OSV-C alone).…”

Section: Discussionmentioning

confidence: 99%

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function

Jang

Shin

Yoon

et al. 2018

J Virol

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Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations ranging from 0.4 to 4.3 M in cells. This compound is a carboxylic polyether ionophore that exchanges monovalent ions for protons across lipid bilayer membranes. Monitoring the time course of viral infection showed that salinomycin blocked nuclear migration of viral nuclear protein (NP), the most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused cytoplasmic accumulation of NP, particularly within perinuclear endosomes, during virus entry. This was primarily associated with failure to acidify the endosomal-lysosomal compartments. Similar to the case with amantadine (AMT), proton channel activity of viral matrix protein 2 (M2) was blocked by salinomycin. Using purified retroviral Gag-based virus-like particles (VLPs) with M2, it was proved that salinomycin directly affects the kinetics of a proton influx into the particles but in a manner different from that of AMT. Notably, oral administration of salinomycin together with the neuraminidase inhibitor oseltamivir phosphate (OSV-P) led to enhanced antiviral effect over that with either compound used alone in influenza A virus-infected mouse models. These results provide a new paradigm for developing antivirals and their combination therapy that control both host and viral factors. IMPORTANCE Influenza virus is a main cause of viral respiratory infection in humans as well as animals, occasionally with high mortality. Circulation of influenza viruses resistant to the matrix protein 2 (M2) inhibitor, amantadine, is highly prevalent. Moreover, the frequency of detection of viruses resistant to the neuraminidase inhibitors, including oseltamivir phosphate (OSV-P) or zanamivir, is also increasing. These issues highlight the need for discovery of new antiviral agents with different mechanisms. Salinomycin as the monovalent cation-proton antiporter exhibited consistent inhibitory effects against influenza A and B viruses. It plays multifunctional roles by blocking endosomal acidification and by inactivating the proton transport function of M2, the key steps for influenza virus uncoating. Notably, salinomycin resulted in marked therapeutic effects in influenza virus-infected mice when combined with OSV-P, suggesting that its chemical derivatives could be developed as an adjuvant antiviral therapy to treat influenza infections resistant or less sensitive to existing drugs.

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Section: Discussionmentioning

confidence: 99%

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function

Jang

Shin

Yoon

et al. 2018

J Virol

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“…After publication of the original article [ 1 ], the authors found that there was an error in the first sentence of the ‘Conclusions’ section: “The combination of CPE with the artemisinins showed a synergistic effect both in vivo and in vitro against P. falciparum 3D7 and P. berghei NK-65, respectively.”…”

Section: Erratum To: Malar J (2016) 15:89 Doi 101186/s12936-016-1137mentioning

confidence: 99%

Erratum to: Synergistic anti-malarial action of cryptolepine and artemisinins

Forkuo

Ansah

Boadu

et al. 2016

Malar J

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“…These are widely used as a source compounds for the synthesis of numerous drugs. Many quinoline based drugs such as Captothecine (anticancer) [2] and Cryptolepine (antimalarial) [3] are available in the market. This skeleton also showed a broad spectrum of biological activities including antiasthmatic [4], antidiabetic [5], antibacterial [6], antitoxoplasma [7], antifungal [8] and anti-HIV [9] activities.…”

Section: Introductionmentioning

confidence: 99%

Detailed analytical studies of 1,2,4-triazole derivatized quinoline

et al. 2019

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The present study describes, the X-ray single crystal analysis of 4-((2-chloro-6-methoxyquinolin-3-yl)methyl)-2-phenyl-2H-1,2,4-triazol-3(4H)-one (TMQ). The crystal data for C19H15ClN4O2: monoclinic, space group P21/n (no. 14), a = 7.3314(15) Å, b = 12.459(3) Å, c = 18.948(4) Å, β = 98.322(9)°, V = 1712.5(6) Å3, Z = 4, T = 296.15 K, μ(MoKα) = 0.245 mm-1, Dcalc = 1.423 g/cm3, 5082 reflections measured (3.926° ≤ 2Θ ≤ 38.556°), 1428 unique (Rint = 0.0545, Rsigma = 0.0574) which were used in all calculations. The final R1 was 0.0423 (I >2σ(I)) and wR2 was 0.1145 (all data). The Density functional theory optimized molecular geometries in TMQ agree closely with those obtained from crystallographic studies. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energy levels and energy gap were calculated by experimental (UV absorption & Cyclic voltammetry) and theoretical studies in two different solvents. The natural bond orbital analysis was performed to understand the molecular interaction on the basis of stability of molecule arising from hyper-conjugative interaction and charge delocalization. Hirshfeld surface and their related fingerprint plots enabled the identification of significant intermolecular interaction. The molecular electrostatic potential analysis provides the visual image of the chemically active sites and comparable reaction of atoms.

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Synergistic anti-malarial action of cryptolepine and artemisinins

Cited by 27 publications

References 30 publications

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function

Erratum to: Synergistic anti-malarial action of cryptolepine and artemisinins

Detailed analytical studies of 1,2,4-triazole derivatized quinoline

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