Efficient synthesis of N-acylbenzotriazoles using tosyl chloride: en route to suberoylanilide hydroxamic acid (SAHA)

Agha, Khalid A.; Abo‐Dya, Nader E.; Ibrahim, Tarek S.; Abdel‐Aal, Eatedal H.

doi:10.3998/ark.5550190.p009.459

Cited by 12 publications

(11 citation statements)

References 7 publications

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“…N -acylbenzotriazoles were synthesized according to reported procedures. The NMR spectra of the reported N -acylbenzotriazoles and their melting points were consistent with their reported values. ,, …”

Section: Methodssupporting

confidence: 87%

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Hybrid N-Acylcysteines as Dual-Acting Matrix Disruptive and Anti-Quorum Sensing Agents Fighting Pseudomonas aeruginosa Biofilms: Design, Synthesis, Molecular Docking Studies, and In Vitro Assays

et al. 2022

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Biofilms facilitate the pathogenesis of life-threatening Pseudomonas aeruginosa infections by coating mucosal surfaces or invasive devices and offer protection from antimicrobial therapy and the host immune response, thus increasing mortality rates and financial burden. Herein, new hybrid N -acylcysteines (NAC) incorporating selected acyl groups from organic acids and their derivatives, which are capable of quenching pathogen quorum sensing (QS) systems, were designed and their antibiofilm activity and anti-QS were evaluated. N -acylcysteines ( 4a–h ) were synthesized and characterized by 1 H NMR and 13 C NMR, and their purity was confirmed by elemental analyses. N -(4-Hydroxy-3,5-dimethoxybenzoyl)- l -cysteine ( 4d ) and N -(4-methoxybenzoyl)- l -cysteine ( 4h ) showed a higher antibiofilm activity against PAO1 biofilms than the rest of the targets and the standard NAC. They showed 83 and 82% inhibition of biofilms at 5 mM and eradicated mature biofilms at 20 mM concentrations (NAC biofilm inhibition = 66% at 10 mM and minimum biofilm eradication concentration = 40 mM). This was confirmed via visualizing adherent biofilm cells on catheter pieces using scanning electron microscopy. In the same vein, both 4d and 4h showed the highest docking score with the QS signal receptor protein LasR (−7.8), which was much higher than that of NAC (−5) but less than the score of the natural agonist N -(3-oxododecanoyl)- l -homoserine (OdDHL) (−8.5). Target 4h (5 mM) decreased the expression of quorum sensing encoding genes in P. aeruginosa PAO1 strain by 53% for pslA , 47% for lasI and lasR , and 29% for filC , lowered PAO1 pyocyanin production by 76.43%, completely blocked the proteolytic activity of PAO1, and did not affect PAO1 cell viability. Targets 4d and 4h may find applications for the prevention and treatment of biofilm-mediated P. aeruginosa local infections of the skin, eye, and wounds. N -(4-Methoxybenzoyl)- l -cysteine 4h is a promising dual-acting matrix disruptive and anti-QS antibiofilm agent for further investigation and optimization.

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Section: Methodssupporting

confidence: 87%

“…The NMR spectra of the reported N -acylbenzotriazoles and their melting points were consistent with their reported values. 30 , 32 , 38 …”

Section: Methodsmentioning

confidence: 99%

Hybrid N-Acylcysteines as Dual-Acting Matrix Disruptive and Anti-Quorum Sensing Agents Fighting Pseudomonas aeruginosa Biofilms: Design, Synthesis, Molecular Docking Studies, and In Vitro Assays

et al. 2022

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“…All the chemicals were purchased from Sigma-Aldrich (Cairo, Egypt) or Lancaster Synthesis Corporation (London, UK). Intermediates 12 – 15a – j [ 38 , 39 , 40 ] and 17 [ 41 , 42 , 43 ], 18 [ 44 , 45 ] were prepared as previously reported.…”

Section: Methodsmentioning

confidence: 99%

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

et al. 2020

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A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.

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“…101–102 °C). 53 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.22 (s, 1H, N = CHC–C = O), 8.90 (d, J = 6.5 Hz, 1H, Ar–H), 8.50–8.48 (m, 1H, Ar–H), 8.33 (dd, J = 17.6 Hz, 8.4 Hz, 2H, Ar–H), 7.86 (t, J = 7.8 Hz, 1H, Ar–H), 7.71–7.66 (m, 2H, Ar–H). 13 C NMR (100 MHz, DMSO-d 6 ) δ 165.3 (C = O), 153.3 (CH–N), 151.3 (N = CH–C–C = O), 145.2 (C–N = N), 138.8 (Ar–C), 131.4 (Ar–C), 130.9 (Ar–C), 128.0 (Ar–C), 126.8 (Ar–C), 123.3 (Ar–C), 120.1 (Ar–C), 114.3 (Ar–C).…”

Section: General Procedures For the Synthesis Of N ...mentioning

confidence: 99%

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

Agha

Abo‐Dya

Issahaku

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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An efficient method for synthesising NMDAR co-agonist Sunifiram (DM235), in addition to Sunifram-carbamate and anthranilamide hybrids, has been developed in high yields via protecting group-free stepwise unsymmetric diacylation of piperazine using N -acylbenzotiazole. Compounds 3f , 3d, and 3i exhibited promising nootropic activity by enhancing acetylecholine (ACh) release in A549 cell line. Moreover, the carbamate hybrid 3f was found to exhibit higher in vitro potency than donepezil with IC 50 = 18 ± 0.2 nM, 29.9 ± 0.15 nM for 3f and donepezil, respectively. 3f was also found to effectively inhibit AChE activity in rat brain (AChE = 1.266 ng/mL) compared to tacrine (AChE = 1.137 ng/ml). An assessment of the ADMET properties revealed that compounds 3f, 3d, and 3i are drug-like and can penetrate blood–brain barrier. Findings presented here showcase highly potential cholinergic agents, with expected partial agonist activity towards glycine binding pocket of NMDAR which could lead to development and optimisation of novel nootropic drugs.

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Efficient synthesis of N-acylbenzotriazoles using tosyl chloride: en route to suberoylanilide hydroxamic acid (SAHA)

Cited by 12 publications

References 7 publications

Hybrid N-Acylcysteines as Dual-Acting Matrix Disruptive and Anti-Quorum Sensing Agents Fighting Pseudomonas aeruginosa Biofilms: Design, Synthesis, Molecular Docking Studies, and In Vitro Assays

Hybrid N-Acylcysteines as Dual-Acting Matrix Disruptive and Anti-Quorum Sensing Agents Fighting Pseudomonas aeruginosa Biofilms: Design, Synthesis, Molecular Docking Studies, and In Vitro Assays

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

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