Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents

Ali, Abdul Aziz; Gogoi, Dhrubajyoti; Chaliha, Amrita Kashyap; Buragohain, Alak Kumar; Trivedi, Priyanka; Saikia, Prakash J.; Gehlot, Praveen Singh; Kumar, Arvind; Chaturvedi, Vinita; Sarma, Diganta

doi:10.1016/j.bmcl.2017.07.008

Cited by 74 publications

(16 citation statements)

References 36 publications

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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%

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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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Section: Resultsmentioning

confidence: 99%

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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“…The emerging role of triazoles on antitumoral and antimicrobial activities 23-26, led us to exploit the 1,3-dipolar cycloaddition reaction (CuAAC: Copper-catalyzed Azide-Alkyne Cycloaddition reaction) to afford a small series of 25 1,2,3-triazole derivatives with chemical diversity based on three cores (Figure 1A-C), amino ethyl-quinoline (01-08), benzyl-piperazine (09-16) and benzyl-piperidine (17)(18)(19)(20)(21)(22)(23)(24)(25). We have synthesized this series in good yields and complete regioselectivity control and initially screened all compounds against HTLV-1-infected cells (MT-2 cell line), using resazurin reduction method, in order to identify cell proliferation inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 The lack of Tax inhibitors favors the screen of compound libraries in order to identify potential prototypes. Click Chemistry is a well-known synthetic strategy that generates 1,2,3-triazole motifs and has been exploited to produce chemical diversity and obtain antitumor 23 , antimicrobial 24 and antiviral agents. 25 In this context, we aimed to identify cell proliferation inhibitors and inducers of apoptosis in a cell-based assay (HTLV-1-infected cell line MT-2) by assessing a series of 25 heterocyclic compounds bearing 1,2,3-triazole motif.…”

Section: Introductionmentioning

confidence: 99%

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Santos

Pilger

Vandermeulen

et al. 2020

Bioorganic & Medicinal Chemistry

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Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10-20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma -ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP).Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥ 70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 were also able to reduce GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL.

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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 biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents

Cited by 74 publications

References 36 publications

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

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

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

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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