CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses
The promising approach toward the synthesis of novel sulfur-based quinoline and benzoquinoline isostere molecules. The condensation reaction involves 4-chloro-2,8-dimethylquinolines or 4-chloro-2-methylbenzo[h]quinoline and corresponding o-thiosalicylic acid and 2-mercaptonicotinic acid, either in e...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Heteroatom Chemistry |
| Online Access: | http://dx.doi.org/10.1155/hc/9933732 |
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| author | Kolandaivel Prabha Satheeshkumar Rajendran Gamze Tüzün Kailasam Saravana Mani Koray Sayin |
| author_facet | Kolandaivel Prabha Satheeshkumar Rajendran Gamze Tüzün Kailasam Saravana Mani Koray Sayin |
| author_sort | Kolandaivel Prabha |
| collection | DOAJ |
| description | The promising approach toward the synthesis of novel sulfur-based quinoline and benzoquinoline isostere molecules. The condensation reaction involves 4-chloro-2,8-dimethylquinolines or 4-chloro-2-methylbenzo[h]quinoline and corresponding o-thiosalicylic acid and 2-mercaptonicotinic acid, either in ethanol (as a solvent) or under solvent-free (neat) conditions. This results in the formation of an intermediate, which yields significantly better results when using neat solvent-free conditions. The intermediates then undergo cyclization using polyphosphoric acid (PPA). Notably, the sulfur-based quinoline and benzoquinoline isosteres are prepared through a highly efficient one-pot methodology using CuI/Cs2CO3/DMSO conditions, which yields higher than the PPA condition through a step-by-step method. The synthesized novel sulfur-containing isosteres are further analyzed through quantum chemical calculations of the frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) using the M06-2X method with a 6-311 + G (d, p) basis set in water. Additionally, in silico analyses are performed in detail to predict the potential biological activity of the synthesized molecules through molecular docking and MM-GBSA analysis against the CDK8/CycC complex. Furthermore, ADME parameters have been analyzed, and all the final cyclized molecules show the most promising drug-like properties, inspiring further research in medicinal chemistry. |
| format | Article |
| id | doaj-art-a739fa808c534e3fbc0cee866b6db161 |
| institution | DOAJ |
| issn | 1098-1071 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Heteroatom Chemistry |
| spelling | doaj-art-a739fa808c534e3fbc0cee866b6db1612025-08-20T03:22:19ZengWileyHeteroatom Chemistry1098-10712025-01-01202510.1155/hc/9933732CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT AnalysesKolandaivel Prabha0Satheeshkumar Rajendran1Gamze Tüzün2Kailasam Saravana Mani3Koray Sayin4Department of Food TechnologyDepartment of ChemistryDepartment of ChemistryCentre for Material ChemistryDepartment of ChemistryThe promising approach toward the synthesis of novel sulfur-based quinoline and benzoquinoline isostere molecules. The condensation reaction involves 4-chloro-2,8-dimethylquinolines or 4-chloro-2-methylbenzo[h]quinoline and corresponding o-thiosalicylic acid and 2-mercaptonicotinic acid, either in ethanol (as a solvent) or under solvent-free (neat) conditions. This results in the formation of an intermediate, which yields significantly better results when using neat solvent-free conditions. The intermediates then undergo cyclization using polyphosphoric acid (PPA). Notably, the sulfur-based quinoline and benzoquinoline isosteres are prepared through a highly efficient one-pot methodology using CuI/Cs2CO3/DMSO conditions, which yields higher than the PPA condition through a step-by-step method. The synthesized novel sulfur-containing isosteres are further analyzed through quantum chemical calculations of the frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) using the M06-2X method with a 6-311 + G (d, p) basis set in water. Additionally, in silico analyses are performed in detail to predict the potential biological activity of the synthesized molecules through molecular docking and MM-GBSA analysis against the CDK8/CycC complex. Furthermore, ADME parameters have been analyzed, and all the final cyclized molecules show the most promising drug-like properties, inspiring further research in medicinal chemistry.http://dx.doi.org/10.1155/hc/9933732 |
| spellingShingle | Kolandaivel Prabha Satheeshkumar Rajendran Gamze Tüzün Kailasam Saravana Mani Koray Sayin CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses Heteroatom Chemistry |
| title | CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses |
| title_full | CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses |
| title_fullStr | CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses |
| title_full_unstemmed | CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses |
| title_short | CuI/PPA-Catalyzed Synthesis of Novel Sulfur-Containing Quinoline Isosteres: In Silico and DFT Analyses |
| title_sort | cui ppa catalyzed synthesis of novel sulfur containing quinoline isosteres in silico and dft analyses |
| url | http://dx.doi.org/10.1155/hc/9933732 |
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