Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme
The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/12/1799 |
| _version_ | 1797461745678155776 |
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| author | Rasha A. Azzam Heba A. Elboshi Galal H. Elgemeie |
| author_facet | Rasha A. Azzam Heba A. Elboshi Galal H. Elgemeie |
| author_sort | Rasha A. Azzam |
| collection | DOAJ |
| description | The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole <i>N</i>-arylsulphonylhydrazone with <i>N</i>-aryl-2-cyano-3-(dimethylamino)acrylamide, <i>N</i>-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of <i>N</i>-arylsulfonylpyridones <b>6a–d</b> (yield 60–70%) and <b>12a</b>–<b>c</b> (yield 50–60%)<b>,</b><i>N</i>-(2-(benzo[<i>d</i>]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide <b>14a</b>–<b>c</b> (yield 60–65%)<b>,</b> 4-(benzo[<i>d</i>]thiazole-2-yl)-5-aryl-1<i>H</i>-pyrazol-3(2<i>H</i>)-one <b>16a</b>–<b>c</b> (yield 65–75%), and <i>N′</i>-(2-(benzo[<i>d</i>]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide <b>19a</b>–<b>e</b> (yield 85–70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against <i>S. aureus</i> with an MIC range of 0.025 to 2.609 mM. The most active compound, <b>16c</b>, exhibited superior activity against the <i>S. aureus</i> strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical–pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical–pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, <b>16a</b>–<b>c</b>, had IC<sub>50</sub> values comparable to the standard drug and revealed that compound <b>16b</b> was the most active compound with an IC<sub>50</sub> value of 7.85 μg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC<sub>50</sub> value of 7.13 μg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds <b>16a</b>–<b>c</b> are linked by two arene-H interactions with Lys220 within the PABA pocket. |
| first_indexed | 2024-03-09T17:23:42Z |
| format | Article |
| id | doaj.art-1308b378baeb44cc9402e32d997553e6 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T17:23:42Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-1308b378baeb44cc9402e32d997553e62023-11-24T12:54:38ZengMDPI AGAntibiotics2079-63822022-12-011112179910.3390/antibiotics11121799Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS EnzymeRasha A. Azzam0Heba A. Elboshi1Galal H. Elgemeie2Chemistry Department, Faculty of Science, Helwan University, Cairo 11795, EgyptChemistry Department, Faculty of Science, Helwan University, Cairo 11795, EgyptChemistry Department, Faculty of Science, Helwan University, Cairo 11795, EgyptThe drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole <i>N</i>-arylsulphonylhydrazone with <i>N</i>-aryl-2-cyano-3-(dimethylamino)acrylamide, <i>N</i>-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of <i>N</i>-arylsulfonylpyridones <b>6a–d</b> (yield 60–70%) and <b>12a</b>–<b>c</b> (yield 50–60%)<b>,</b><i>N</i>-(2-(benzo[<i>d</i>]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide <b>14a</b>–<b>c</b> (yield 60–65%)<b>,</b> 4-(benzo[<i>d</i>]thiazole-2-yl)-5-aryl-1<i>H</i>-pyrazol-3(2<i>H</i>)-one <b>16a</b>–<b>c</b> (yield 65–75%), and <i>N′</i>-(2-(benzo[<i>d</i>]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide <b>19a</b>–<b>e</b> (yield 85–70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against <i>S. aureus</i> with an MIC range of 0.025 to 2.609 mM. The most active compound, <b>16c</b>, exhibited superior activity against the <i>S. aureus</i> strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical–pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical–pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, <b>16a</b>–<b>c</b>, had IC<sub>50</sub> values comparable to the standard drug and revealed that compound <b>16b</b> was the most active compound with an IC<sub>50</sub> value of 7.85 μg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC<sub>50</sub> value of 7.13 μg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds <b>16a</b>–<b>c</b> are linked by two arene-H interactions with Lys220 within the PABA pocket.https://www.mdpi.com/2079-6382/11/12/1799benzothiazolesulfonamideantimicrobial evaluationdocking studyphysicochemical properties |
| spellingShingle | Rasha A. Azzam Heba A. Elboshi Galal H. Elgemeie Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme Antibiotics benzothiazole sulfonamide antimicrobial evaluation docking study physicochemical properties |
| title | Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme |
| title_full | Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme |
| title_fullStr | Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme |
| title_full_unstemmed | Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme |
| title_short | Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme |
| title_sort | synthesis physicochemical properties and molecular docking of new benzothiazole derivatives as antimicrobial agents targeting dhps enzyme |
| topic | benzothiazole sulfonamide antimicrobial evaluation docking study physicochemical properties |
| url | https://www.mdpi.com/2079-6382/11/12/1799 |
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