New bis(pyrazolo[3,4-b]pyridines) and bis(thieno[2,3-b]pyridines) as potential acetylcholinesterase inhibitors: synthesis, in vitro and SwissADME prediction study

Ahmed, Ahmed A. M.; Mekky, Ahmed E. M.; Sanad, Sherif M. H.

doi:10.1007/s13738-022-02614-8

Cited by 10 publications

(2 citation statements)

References 68 publications

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“…Numerous publications described the fascinating AChE inhibitory activity of thieno [2,3-b]pyridines (See Figure 2). [16][17][18] Additionally, the previous hybrids demonstrated interesting biological applications, including antimicrobial, [19][20][21] antiviral, [22,23] anti-inflammatory, [24][25][26] and antidiabetic activity. [27] They also act as effective inhibitors of DNA gyrase, [28] and COX-2 enzymes.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐Mediated Synthesis of New (Piperazine‐Chromene)‐Linked Bis(thieno[2,3‐b]pyridine) Hybrids as Potential Anti‐acetylcholinesterase

Sanad

Mekky

2022

ChemistrySelect

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Using ultrasound irradiation and the eco-friendly piperazine, two series of (piperazine-chromene)-linked bis (thieno[2,3b]pyridine) hybrids attached to various arene or chromene units were efficiently prepared. Therefore, the target hybrids were prepared by reacting bis(pyridine-2(1H)-thione) with two equivalents of the appropriate α-haloketones in the presence of 1.4 equivalents of piperazine. The reaction mixture was subjected to ultrasonic irradiations at 60 °C for 20-40 min to produce the desired products in 87-96 % yields. At concentrations of 15 and 25 μM, new hybrids were tested for antiacetylcholinesterase activity, as well as their ability to quench DPPH free radicals at a concentration of 25 μg/mL. Generally, the chromene unit attached to thienopyridine-C2 has a significant effect on the inhibitory activity of the new hybrids. Moreover, the electronic properties of the substituent attached to the chromene-C6 unit influence the inhibitory activity. The bis(thienopyridine) hybrid attached to 6-methoxy-2H-chromen-2-one units demonstrated the best anti-acetylcholinesterase activity at the previous concentrations, with inhibition percentages of 69.1 and 85.4. Additionally, with an inhibition percentage of 84.4, the previous hybrid demonstrated the most effective anti-DPPH activity.

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Section: Introductionmentioning

confidence: 99%

Ultrasound‐Mediated Synthesis of New (Piperazine‐Chromene)‐Linked Bis(thieno[2,3‐b]pyridine) Hybrids as Potential Anti‐acetylcholinesterase

Sanad

Mekky

2022

ChemistrySelect

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“…[54] As a potential metronidazole mimic, the fascinating biological activities of scaffolds-based 2,5dimethyl-1H-1-phenylpyrrole, including hybrids VII-IX, have been established in numerous publications. [55][56][57] In light of the aforementioned findings, as well as our ongoing efforts to synthesize bioactive azoles, [58][59][60][61][62][63] we aimed in this study to prepare potential TS inhibitors by coupling 1,3,4-oxadiazole and 2,5-dimethyl-1H-1-phenylpyrrole units to mimic the 5-FU and metronidazole structures (see Figure 2). The potential cytotoxicity of the new hybrids is tested in vitro against some selected carcinoma cell lines.…”

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confidence: 99%

Tandem synthesis, cytotoxicity, and in silico study of new 1,3,4‐oxadiazoles as potential thymidylate synthase inhibitors

Sanad

Mekky

Ahmed

2022

Archiv der Pharmazie

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A new series of pyrrole-linked mono-and bis(1,3,4-oxadiazole) hybrids, attached to various arene units, was prepared using a two-step tandem protocol. Therefore, a benzohydrazide derivative was condensed with the appropriate aldehydes in ethanol at 80°C for 60-150 min to give the corresponding N-(benzoylhydrazones). Without isolation, the previous intermediates underwent intramolecular oxidative cyclization in dimethyl sulfoxide at 180°C for 90-200 min in the presence of chloramine trihydrate to afford the target hybrids. The cytotoxicity of all hybrids was examined in vitro against the MCF-7, HEPG2, and Caco2 cell lines. Arene-linked hybrids 4i and 4j, attached to p-nitro and pacetoxy units, were the most potent ones, with IC 50 values ranging from 5.47 to 8.80 and 12.75 to 21.22 μM, respectively, when tested on the above cell lines. At the tested concentrations of 5 and 7.5 μM, hybrid 4i inhibited thymidylate synthase (TS) with the best inhibition percentages of 72.3 and 91.3, whereas hybrid 4j displayed comparable inhibitory activity to the reference pemetrexed. Hybrid 4j had inhibition percentages of 62.7 and 82.6, whereas pemetrexed had inhibition percentages of 59.2 and 80.2, respectively. The capability of hybrids 4i and 4j as potential TS inhibitors is supported by molecular docking studies, while SwissADME predicts their efficacy as drug-like scaffolds.

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New Bis(pyrazolo[5,1‐b]quinazolines) and Bis(9H‐xanthenediones) Linked to Alkane Cores: One‐Pot Synthesis, Antibacterial Screening, and SAR Study

Mekky,

Sanad

2024

Chemistry & Biodiversity

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Effective one‐pot methods were used to synthesize some new alkane‐linked bis(pyrazolo[5,1‐b]quinazolines) and bis(9H‐xanthenediones). The first series was produced, in 80‐88% yields, via the reaction of one equivalent of the appropriate bis(aldehydes) with two equivalents of 1H‐pyrazole‐3,5‐diamine and dimedone in DMF at 150 ºC for 5‐6 h. The second series was prepared, in 82‐89% yields, via the reaction one equivalent of the appropriate bis(aldehydes) with four equivalents of dimedone in acetic acid at 120 ºC for 4‐5 h. The new products displayed a broad range of antibacterial activity against different bacterial strains. Generally, the antibacterial activity of the alkane‐linked bis(pyrazolo[5,1‐b]quinazoline) units is more than 2‐fold their bis(9H‐xanthenedione) analogues. The (p‐tolylthio)methyl)‐linked bis(pyrazolo[5,1‐b]quinazolines) demonstrate the best antibacterial activity with MIC/MBC values up to 3.3/6.6 µM.

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New bis(pyrazolo[3,4-b]pyridines) and bis(thieno[2,3-b]pyridines) as potential acetylcholinesterase inhibitors: synthesis, in vitro and SwissADME prediction study

Cited by 10 publications

References 68 publications

Ultrasound‐Mediated Synthesis of New (Piperazine‐Chromene)‐Linked Bis(thieno[2,3‐b]pyridine) Hybrids as Potential Anti‐acetylcholinesterase

Ultrasound‐Mediated Synthesis of New (Piperazine‐Chromene)‐Linked Bis(thieno[2,3‐b]pyridine) Hybrids as Potential Anti‐acetylcholinesterase

Tandem synthesis, cytotoxicity, and in silico study of new 1,3,4‐oxadiazoles as potential thymidylate synthase inhibitors

New Bis(pyrazolo[5,1‐b]quinazolines) and Bis(9H‐xanthenediones) Linked to Alkane Cores: One‐Pot Synthesis, Antibacterial Screening, and SAR Study

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