New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties

Eddahmi, Mohammed; Sousa, Vera; Moura, Nuno M. M.; Dias, Cristina J.; Bouissane, Latifa; Faustino, Maria A. F.; Cavaleiro, José A. S.; Gomes, Ana T. P. C.; Almeida, Adelaide; Neves, Maria G. P. M. S.; Rakib, El Mostapha

doi:10.1016/j.bioorg.2020.103994

Cited by 6 publications

(3 citation statements)

References 70 publications

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“…In our pursuit to develop new bioactive molecules based on indazole units, − we report here an efficient one-pot synthesis of amino-thiazoloindazole with excellent yields. By performing Mondrian conformal target prediction with the ChEMBL database, we identified AChE as a particularly promising target for the activity of amino-thiazoloindazole derivatives.…”

Section: Introductionmentioning

confidence: 99%

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights

Laghchioua,

da Silva,

Pinto

et al. 2024

ACS Chem. Neurosci.

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Alzheimer's disease is characterized by a progressive deterioration of cognitive function and memory loss, and it is closely associated with the dysregulation of cholinergic neurotransmission. Since acetylcholinesterase (AChE) is a critical enzyme in the nervous system, responsible for breaking down the neurotransmitter acetylcholine, its inhibition holds a significant interest in the treatment of various neurological disorders. Therefore, it is crucial to develop efficient AChE inhibitors capable of increasing acetylcholine levels, ultimately leading to improved cholinergic neurotransmission. The results reported here represent a step forward in the development of novel thiazoloindazole-based compounds that have the potential to serve as effective AChE inhibitors. Molecular docking studies revealed that certain of the evaluated nitroindazole-based compounds outperformed donepezil, a well-known AChE inhibitor used in Alzheimer's disease treatment. Sustained by these findings, two series of compounds were synthesized. One series included a triazole moiety (Tl45a−c), while the other incorporated a carbazole moiety (Tl58a−c). These compounds were isolated in yields ranging from 66 to 87% through nucleophilic substitution and Cu(I)-catalyzed azide−alkyne 1,3dipolar cycloaddition (CuAAC) reactions. Among the synthesized compounds, the thiazoloindazole-based 6b core derivatives emerged as selective AChE inhibitors, exhibiting remarkable IC 50 values of less than 1.0 μM. Notably, derivative Tl45b displays superior performance as an AChE inhibitor, boasting the lowest IC 50 (0.071 ± 0.014 μM). Structure−activity relationship (SAR) analysis indicated that derivatives containing the bis(trifluoromethyl)phenyl-triazolyl group demonstrated the most promising activity against AChE, when compared to more rigid substituents such as carbazolyl moiety. The combination of molecular docking and experimental synthesis provides a suitable and promising strategy for the development of new efficient thiazoloindazole-based AChE inhibitors.

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Section: Introductionmentioning

confidence: 99%

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights

Laghchioua,

da Silva,

Pinto

et al. 2024

ACS Chem. Neurosci.

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“…Our interest is centered on the functionalization of β-pyrrolic positions of meso -tetraarylporphyrins aiming to prepare new porphyrinic derivatives with adequate properties to be used in different fields [ 57 ], namely as photosensitizers in Photodynamic Therapy (PDT) or antimicrobial PDT [ 13 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. We then report here an efficient synthetic approach to obtain a novel series of mononuclear heteroleptic porphyrin-iridium(III) complexes 4 and 5 via porphyrin derivatives 2 bearing a bipyridine unit (see Scheme 1 and Scheme 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…, and H-4 C ), 6.76-6.64 (4H, m, H-5 C , H-5 F , H-4 E , and H-2 G , 6 G ), 6 59. 6.53 (2H, m, H-5 E , and H-4 D ), 6.29 (1H, td, J = 7.6 and 1.2 Hz, H-5 D ), 6.00 (1H, d, J = 7.5 Hz, H-6 C ), 5.85 (1H, d, J = 7.1 Hz, 6 E ), 5.48 (1H, d, J = 7.4 Hz, H-6 D ) ppm.…”

mentioning

confidence: 99%

New Bis-Cyclometalated Iridium(III) Complexes with β-Substituted Porphyrin-Arylbipyridine as the Ancillary Ligand: Electrochemical and Photophysical Insights

Moura

Serra

Bastos

et al. 2022

IJMS

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An efficient synthetic access to new cationic porphyrin-bipyridine iridium(III) bis-cyclometalated complexes was developed. These porphyrins bearing arylbipyridine moieties at β-pyrrolic positions coordinated with iridium(III), and the corresponding Zn(II) porphyrin complexes were spectroscopically, electrochemically, and electronically characterized. The features displayed by the new cyclometalated porphyrin-bipyridine iridium(III) complexes, namely photoinduced electron transfer process (PET), and a remarkable efficiency to generate 1O2, allowing us to envisage new challenges and opportunities for their applications in several fields, such as photo(catalysis) and photodynamic therapies.

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Study of N‐methyl‐5‐nitroindazolylacrylonitriles as a Function of Quantum Parameters Employing Density Function Theory Methods: Comparative Theoretical Study and Nonlinear Optical Properties

et al. 2023

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The synthesis of N-methyl-5-nitroindazolylacrylonitriles 2 a-l by a Knoevenagel condensation reaction with a series of aldehydes in the presence of piperidine allowed the preparation of the desired products the yields are good to excellent. N-Methyl-5-nitroindazolylacrylonitriles (2 a-l) were verified by 1 H, 13 C NMR and mass spectrometry. In this current work, the reactivity indices defined within the Conceptual DFT of the targeted molecules through DFT/B3LYP/6-311G(d,p) calculations were studied. The 1 H NMR, UV-vis and IR spectroscopy chemical shifts of all synthesized 5-nitroindazoles 2 a-l were calculated and the results were compared to the results of the experimental data. In this series of compounds, the 2 e has the lowest hyperpolarizability, which results being the most stable and having the least response to nonlinear optics (NLO). In contrast, the compound 2 l has the highest hyperpolarizability, which fallouts being the least stable and having a high response to NLO. Every chemical has a significant threedimensional p-electronic delocalization, which is crucial for understanding NLO responses.

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New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties

Cited by 6 publications

References 70 publications

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights

New Bis-Cyclometalated Iridium(III) Complexes with β-Substituted Porphyrin-Arylbipyridine as the Ancillary Ligand: Electrochemical and Photophysical Insights

Study of N‐methyl‐5‐nitroindazolylacrylonitriles as a Function of Quantum Parameters Employing Density Function Theory Methods: Comparative Theoretical Study and Nonlinear Optical Properties

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