Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4-{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides
| Autor: | Aziz Ur Rehman, Muhammad Athar Abbasi, Mubashir Hassan, Sung-Yum Seo, Ayesha Mumtaz, Hussain Raza, Sahahat Zahra Siddiqui, Majid Nazir, Syed Adnan Ali Shah |
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| Rok vydání: | 2018 |
| Předmět: |
01 natural sciences
Medicinal chemistry Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Picrates Acetamides Drug Discovery Nucleophilic substitution Enzyme Inhibitors Enzyme Assays Plant Proteins Sulfonyl chemistry.chemical_classification Sulfonamides Aqueous solution biology 010405 organic chemistry Biphenyl Compounds Active site Free Radical Scavengers General Medicine Urease 0104 chemical sciences Molecular Docking Simulation Canavalia Oxidative Stress Thiourea chemistry 030220 oncology & carcinogenesis biology.protein Benzenesulfonyl chloride Dimethylformamide Acetamide |
| Zdroj: | Drug Research. 69:111-120 |
| ISSN: | 2194-9387 2194-9379 |
| DOI: | 10.1055/a-0654-5074 |
| Popis: | In this study, a new series of sulfonamides derivatives was synthesized and their inhibitory effects on DPPH and jack bean urease were evaluated. The in silico studies were also applied to ascertain the interactions of these molecules with active site of the enzyme. Synthesis was initiated by the nucleophilic substitution reaction of 2-(4-methoxyphenyl)-1-ethanamine (1) with 4-(acetylamino)benzenesulfonyl chloride (2) in aqueous sodium carbonate at pH 9. Precipitates collected were washed and dried to obtain the parent molecule, N-(4-{[(4-methoxyphenethyl)amino]sulfonyl}phenyl)acetamide (3). Then, this parent was reacted with different alkyl/aralkyl halides, (4a-m), using dimethylformamide (DMF) as solvent and LiH as an activator to produce a series of new N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides (5a-m). All the synthesized compounds were characterized by IR, EI-MS, 1H-NMR, 13C-NMR and CHN analysis data. All of the synthesized compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5 f exhibited very excellent enzyme inhibitory activity with IC50 value of 0.0171±0.0070 µM relative to standard thiourea having IC50 value of 4.7455±0.0546 µM. Molecular docking studies suggested that ligands have good binding energy values and bind within the active region of taget protein. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski’ rule. |
| Databáze: | OpenAIRE |
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