Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling
A library of chlorophenyl, thiophenyl, and biphenyl clubbed 3′,4,4′,5-tetrahydro-2′H-[1,3′-bipyrazole]-2′-carbaldehydes was produced via aldolic condensation followed by hetero-cyclization. Synthesized moieties were characterized by IR, 1H, and 13CNMR spectral analysis. The molecular docking was con...
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Elsevier
2024-12-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022424002573 |
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| author | Avika Nitin Kumar Haya Yasin Shikha Sharma Suraj N. Mali Shailesh S. Gurav |
| author_facet | Avika Nitin Kumar Haya Yasin Shikha Sharma Suraj N. Mali Shailesh S. Gurav |
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| description | A library of chlorophenyl, thiophenyl, and biphenyl clubbed 3′,4,4′,5-tetrahydro-2′H-[1,3′-bipyrazole]-2′-carbaldehydes was produced via aldolic condensation followed by hetero-cyclization. Synthesized moieties were characterized by IR, 1H, and 13CNMR spectral analysis. The molecular docking was conducted utilizing microbial target proteins, 1JX9, and 5C1P to explore the binding interactions of scaffolds. Analogues 4f, 4l, 4r, and 4x exhibited the best docking score of -10.3 kcal/mol with 1JX9 whereas scaffolds 4l and 4o showed maximum docking of -10.4 and -10.2 kcal/mol with target protein 5C1P. Further, scaffolds 4f, 4I, 4l, 4o, 4 u, and 4v showed excellent (pMIC: 1.92 µM/mL) antibacterial activity against S. aureus, B. subtilis, E. coli, P. aeruginosa whereas; analogues 4c, 4l, 4o, 4r, and 4v exhibited admirable (pMIC: 1.92 µM/mL) antifungal activity against R. oryzae fungal strain. Also, analogues were tested for their radical scavenging ability and 4a, 4 g, 4i, 4p, and 4x exhibited good antioxidant activity with 4i standing out as a propitious scaffold with 93.25 % radical scavenging activity. SAR study revealed that biphenyl, 4‑hydroxy-3‑methoxy phenyl, and thiophenyl moieties on the bipyrazole-carbaldehyde scaffold are accountable for virtuous antibacterial, antifungal, and antioxidant activity, respectively. Further in-silico ADME, pharmacokinetic, and toxicity properties were studied, forecasting less-toxic analogues (300 < LD50 ≤ 5000). These findings collectively underscore the potential of the synthesized compounds, with 4l, 4o, 4v and 4x standing out as particularly promising candidates for further exploration. |
| format | Article |
| id | doaj-art-fc99ec4e4f9a4b95ade7f60bfc10cde7 |
| institution | Kabale University |
| issn | 2667-0224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-fc99ec4e4f9a4b95ade7f60bfc10cde72024-11-27T05:03:37ZengElsevierChemical Physics Impact2667-02242024-12-019100713Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling Avika0Nitin Kumar1Haya Yasin2Shikha Sharma3Suraj N. Mali4Shailesh S. Gurav5Department of Pharmaceutical Science Lords University Alwar, Rajasthan 301028, IndiaDepartment of Pharmaceutical Science Lords University Alwar, Rajasthan 301028, IndiaCorresponding authors.; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab EmiratesDepartment of Pharmaceutical Science Lords University Alwar, Rajasthan 301028, India; Corresponding authors.School of Pharmacy, D.Y. Patil University (Deemed to be University), Sector 7, Nerul, Navi Mumbai 400706, India; Corresponding authors.Department of Chemistry, VIVA College, Virar (W), Maharashtra 401303, India; Corresponding authors.A library of chlorophenyl, thiophenyl, and biphenyl clubbed 3′,4,4′,5-tetrahydro-2′H-[1,3′-bipyrazole]-2′-carbaldehydes was produced via aldolic condensation followed by hetero-cyclization. Synthesized moieties were characterized by IR, 1H, and 13CNMR spectral analysis. The molecular docking was conducted utilizing microbial target proteins, 1JX9, and 5C1P to explore the binding interactions of scaffolds. Analogues 4f, 4l, 4r, and 4x exhibited the best docking score of -10.3 kcal/mol with 1JX9 whereas scaffolds 4l and 4o showed maximum docking of -10.4 and -10.2 kcal/mol with target protein 5C1P. Further, scaffolds 4f, 4I, 4l, 4o, 4 u, and 4v showed excellent (pMIC: 1.92 µM/mL) antibacterial activity against S. aureus, B. subtilis, E. coli, P. aeruginosa whereas; analogues 4c, 4l, 4o, 4r, and 4v exhibited admirable (pMIC: 1.92 µM/mL) antifungal activity against R. oryzae fungal strain. Also, analogues were tested for their radical scavenging ability and 4a, 4 g, 4i, 4p, and 4x exhibited good antioxidant activity with 4i standing out as a propitious scaffold with 93.25 % radical scavenging activity. SAR study revealed that biphenyl, 4‑hydroxy-3‑methoxy phenyl, and thiophenyl moieties on the bipyrazole-carbaldehyde scaffold are accountable for virtuous antibacterial, antifungal, and antioxidant activity, respectively. Further in-silico ADME, pharmacokinetic, and toxicity properties were studied, forecasting less-toxic analogues (300 < LD50 ≤ 5000). These findings collectively underscore the potential of the synthesized compounds, with 4l, 4o, 4v and 4x standing out as particularly promising candidates for further exploration.http://www.sciencedirect.com/science/article/pii/S2667022424002573Bipyrazole carbaldehydesAntimicrobial and antioxidant activityADMEMolecular dockingSAR studyToxicity |
| spellingShingle | Avika Nitin Kumar Haya Yasin Shikha Sharma Suraj N. Mali Shailesh S. Gurav Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling Chemical Physics Impact Bipyrazole carbaldehydes Antimicrobial and antioxidant activity ADME Molecular docking SAR study Toxicity |
| title | Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling |
| title_full | Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling |
| title_fullStr | Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling |
| title_full_unstemmed | Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling |
| title_short | Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling |
| title_sort | studies on chlorophenyl thiophenyl and biphenyl clubbed tetrahydro bipyrazole carbaldehydes synthesis antimicrobial and antioxidant activity sar study in silico pharmacokinetics toxicity and molecular modeling |
| topic | Bipyrazole carbaldehydes Antimicrobial and antioxidant activity ADME Molecular docking SAR study Toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424002573 |
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