Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

Smit, Frans J.; Seldon, Ronnett; Aucamp, Janine; Jordaan, Audrey; Warner, Digby F.; N’Da, David D.

doi:10.1007/s00044-019-02458-7

Cited by 24 publications

(10 citation statements)

References 56 publications

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“…The BnTz derivatives (Table 1) were previously synthesised, and their lipophilicity data have been reported (Smit et al 2019). However, lipophilicity alongside electronegativity was included in the current investigation as parameters susceptible to impact the antitoxoplasmosis activity of the compounds.…”

Section: Chemistrymentioning

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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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: Chemistrymentioning

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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“…These tunable rings are being researched for drug evolution, as 1,2,3-triazoles can be structurally modified and investigated for their activity against several pharmacological targets to achieve desired molecules targeting a particular disease [17][18][19][20]. The 1,2,3-triazole cores can be found in many FDA-approved drugs such as rufinamide (anticonvulsant), TSAO(antiHIV), cefatrizine (antibiotic), tazobactam (antibacterial), CAI (anticancer), and ribavirin analogs (antiviral) [21][22][23][24]. This inspired us to synthesize new SBs clubbed to a 1,2,3-triazole core and chemically characterized using DFT calculations.…”

Section: Resultsmentioning

confidence: 99%

“…The 1,2,3-triazole cores can be found in many FDA-approved drugs such as rufinamide (anticonvulsant), TSAO (antiHIV), cefatrizine (antibiotic), tazobactam (antibacterial), CAI (anticancer), and ribavirin analogs (antiviral) [ 21 , 22 , 23 , 24 ]. This inspired us to synthesize new SBs clubbed to a 1,2,3-triazole core and chemically characterized using DFT calculations.…”

Section: Introductionmentioning

confidence: 99%

New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects

et al. 2021

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Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of trans-E and cis-E diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the trans-trans form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the trans-trans on one side and syn-syn and syn-trans isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor N3 and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.

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“…1,2,3-triazoles have also marked their position as a significant pharmacophore from nitrogen rich heterocyclic compounds with spectacular therapeutic potential [ 17 , 18 ]. Rufinamide (anticonvulsant), TSAO (anti-HIV), cefatrizine (antibiotic), tazobactam (antibacterial), and CAI (anticancer) are some of the FDA approved drugs bearing 1,2,3-triazole moiety [ 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations

Al-blewi

Shaikh

Naqvi

et al. 2021

IJMS

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A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains 4a–k and 6a–e. After full spectroscopic characterization using different spectral techniques (IR, 1H, 13C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, 4k and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.

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Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

Cited by 24 publications

References 56 publications

In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

In vitro anti-Toxoplasma gondii efficacy of synthesised benzyltriazole derivatives

New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects

Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations

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