Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii

Sanford, Austin G; Schulze, Thomas; Potluri, Lakshmi-Prasad; Watson, Gabrielle F.; Darner, Elyssa B; Zach, Sydney J.; Hemsley, Ryan M.; Wallick, Alexander; Warner, Rosalie C.; Charman, Susan A.; Wang, X.; Vennerstrom, Jonathan L.; Davis, Paul H.

doi:10.1016/j.ijpddr.2018.11.001

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Another interesting finding of this study is the activity of isoniazid. In vitro inhibition of this mainstay anti-TB drug against T. gondii has previously been reported (Sanford et al 2018). In this study, FJS-INH was efficient on T. gondii growth inhibition, although threefold less potent than the leading BnTz derivative.…”

Section: Compd Structuresupporting

confidence: 51%

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In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

Guo

Gao

N’Da

et al. 2021

Onderstepoort Journal of Veterinary Research

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Toxoplasma gondii, an obligate intracellular parasite, is the aetiological agent of toxoplasmosis, a disease that affects approximately 25% – 30% of the world’s population. At present, no safe and effective vaccine exists for the prevention of toxoplasmosis. Current treatment options for toxoplasmosis are active only against tachyzoites and may also cause bone marrow toxicity. To contribute to the global search for novel agents for the treatment of toxoplasmosis, we herein report the in vitro activities of previously synthesised benzyltriazole derivatives. The effects of these compounds against T. gondii in vitro were evaluated by using a expressing green fluorescent protein (GFP) type I strain parasite (RH-GFP) and a type II cyst-forming strain of parasite (PruΔku80Δhxgprt). The frontline antitubercular drug isoniazid, designated as Frans J. Smit -isoniazid (FJS-INH), was also included in the screening as a preliminary test in view of future repurposing of this agent. Of the compounds screened, FJS-302, FJS-303, FJS-403 and FJS-INH demonstrated 80% parasite growth inhibition with IC50 values of 5.6 µg/mL, 6.8 µg/µL, 7.0 µg/mL and 19.8 µg/mL, respectively. FJS-302, FJS-303 and FJS-403 inhibited parasite invasion and replication, whereas, sulphadiazine (SFZ), the positive control, was only effective against parasite replication. In addition, SFZ induced bradyzoite differentiation in vitro, whilst FJS-302, FJS-303 and FJS-403 did not increase the bradyzoite number. These results indicate that FJS-302, FJS-303 and FJS-403 have the potential to act as a viable source of antiparasitic therapeutic agents.

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Section: Compd Structuresupporting

confidence: 51%

“…The synthesised BnTz derivatives were screened for their T. gondii growth inhibitory effects at a final concentration of 50 µg/mL alongside the reference drug SFZ (Sanford et al 2018). The frontline anti-TB drug isoniazid, herein designated…”

Section: Screening Of Chemical Compounds For Anti-toxoplasma Efficacymentioning

confidence: 99%

In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

Guo

Gao

N’Da

et al. 2021

Onderstepoort Journal of Veterinary Research

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“…Among them, molecule 7 with an SI > 148.28, 2 with an SI > 118.93, 8 with an SI > 110.67, and 12 with an SI > 94.59 are the most effective. Thus, it might be concluded that TZD hybrid compounds present comparably or even better anti-Tg potency compared to those recently reported hybrid compounds with thiazolidinone [50,51], TSC [52,53] or PCH [54] structural scaffolds.…”

Section: Ic50tg [µG/ml]mentioning

confidence: 82%

TZD-Based Hybrid Molecules Act as Dual Anti-Mycobacterium tuberculosis and Anti-Toxoplasma gondii Agents

Dzitko

Kaproń

Paneth

et al. 2023

IJMS

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Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molecule 2 proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood–brain barrier (BBB), which is a critical factor linked with ideal anti-Tg drug development. Finally, since a possible link between Tg infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule 2 was found to be the most effective, with an IC50 of 19.36 ± 1.13 µg/mL against T98G cells.

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“…The development of new molecules with drug activity and without dangerous side effects is one of the major challenges of science. The compounds having a hydrazone unit -C=N-NH-R are characterized by their use in the synthesis of compounds having therapeutic properties [1][2][3][4]. Compounds with antibacterial [5,6], antifungal [7], antiviral [8], and anticancer [9] properties are listed.…”

Section: Introductionmentioning

confidence: 99%

Crystal structures of bis-{N-[1-(pyridin-2-yl-κN)ethylidene]nicotine hydrazide-κ2N’,O}cobalt(II)bis(perchlorate) dihydrate and bis-{N'-[1-(pyridin-2-yl-κN)ethylidene]nicotinohydrazide-κ2N',O}copper(II) perchlorate

et al. 2021

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Complexes of Co(II), [Co(C26H24N8O2)]·(ClO4)2·(H2O)2 (1), and Cu(II), [Cu(C26H23N8O2)]·(ClO4) (2), have been synthesized. The prepared two compounds were characterized by elemental analysis, infrared and their structures were determined by single-crystal X-ray diffraction. The compound 1 crystallizes in the triclinic space group P-1 with the following unit cell parameters: a = 8.880 (5) Å, b = 10.529 (5) Å, c = 18.430 (5) Å, α = 99.407 (5)°, β = 102.174 (5)°, γ = 100.652 (5)°, V = 1618.2 (13) Å3, Z = 2, T = 293(2), μ(MoKα) = 0.77 mm-1, Dcalc = 1.582 g/cm3, 16135 reflections measured (5.050° ≤ 2q ≤ 59.152°), 7648 unique, Rint = 0.034 which were used in all calculations. The final R1 was 0.066 (I ≥ 2σ(I)) and wR2 was 0.22 (all data). The compound 2 crystallizes in the monoclinic space group P21/c with the following unit cell parameters : a = 11.652 (5) Å, b = 16.540 (5) Å, c = 14.512 (5) Å, β = 93.495 (5)°, V = 2791.6 (18) Å3, Z = 4, T = 293(2), μ(MoKα) = 1.05 mm-1, Dcalc = 1.768 g/cm3, 15592 reflections measured (5.624° ≤ 2θ ≤ 58.804°), 6630 unique, Rint = 0.025 which were used in all calculations. The final R1 was 0.050 (I ≥ 2σ(I)) and wR2 was 0.144 (all data). In both complexes, the ligand acts in a tridentate fashion. In the structure of the mononuclear complex 1, the Co(II) cation is coordinated by two ligand molecules. The basal plane around the Co(II) cation is occupied by two pyridine nitrogen atoms and two carbonyl oxygen atoms. Two imino nitrogen atoms occupy the apical positions of the distorted square-pyramidal geometry. The mononuclear 2 consists of a Cu(II) coordinated by one ligand and one monodeprotonated ligand molecule. The metal center lies in a distorted square bipyramidal environment. The basal plane around the Cu(II) is occupied by two pyridine nitrogen atoms and two carbonyl oxygen atoms, the apical position being occupied by the two imino nitrogen atoms.

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Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii

Cited by 6 publications

References 15 publications

In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

TZD-Based Hybrid Molecules Act as Dual Anti-Mycobacterium tuberculosis and Anti-Toxoplasma gondii Agents

Crystal structures of bis-{N-[1-(pyridin-2-yl-κN)ethylidene]nicotine hydrazide-κ2N’,O}cobalt(II)bis(perchlorate) dihydrate and bis-{N'-[1-(pyridin-2-yl-κN)ethylidene]nicotinohydrazide-κ2N',O}copper(II) perchlorate

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