Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors
Some (<i>E</i>)-3-(3-(4-(benzyloxy)phenyl)-1-phenyl-1<i>H</i>-pyrazol-4-yl)-1-phenylprop-2-en-1-one conjugates <b>5a</b>–<b>r</b> were designed; synthesized; characterized by <sup>1</sup>H, <sup>13</sup>C NMR, and ESI-MS; and ev...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/3/280 |
| _version_ | 1797443680209993728 |
|---|---|
| author | Md. Jahangir Alam Ozair Alam Ahmad Perwez Moshahid Alam Rizvi Mohd Javed Naim Vegi G. M. Naidu Mohd Imran Mohammed M. Ghoneim Sultan Alshehri Faiyaz Shakeel |
| author_facet | Md. Jahangir Alam Ozair Alam Ahmad Perwez Moshahid Alam Rizvi Mohd Javed Naim Vegi G. M. Naidu Mohd Imran Mohammed M. Ghoneim Sultan Alshehri Faiyaz Shakeel |
| author_sort | Md. Jahangir Alam |
| collection | DOAJ |
| description | Some (<i>E</i>)-3-(3-(4-(benzyloxy)phenyl)-1-phenyl-1<i>H</i>-pyrazol-4-yl)-1-phenylprop-2-en-1-one conjugates <b>5a</b>–<b>r</b> were designed; synthesized; characterized by <sup>1</sup>H, <sup>13</sup>C NMR, and ESI-MS; and evaluated for tubulin polymerization inhibitory activity and in vitro cytotoxicity against breast (MCF-7), cervical (SiHa), and prostate (PC-3) cancer cell lines, as well as a normal cell line (HEK-293T). The compounds were also tested to determine their binding modes at the colchicine-binding site of tubulin protein (PDB ID-3E22), for in silico ADME prediction, for bioactivity study, and for PASS prediction studies. Among all the synthesized conjugates, compound <b>5o</b> exhibited excellent cytotoxicity with an IC<sub>50</sub> value of 2.13 ± 0.80 µM (MCF-7), 4.34 ± 0.98 µM (SiHa), and 4.46 ± 0.53 µM (PC-3) against cancer cell lines. The compound did not exhibit significant toxicity to the HEK cells. Results of the in silico prediction revealed that the majority of the conjugates possessed drug-like properties. |
| first_indexed | 2024-03-09T13:01:32Z |
| format | Article |
| id | doaj.art-2f2a169b12e640f0a659a9341b0d9fdc |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:01:32Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-2f2a169b12e640f0a659a9341b0d9fdc2023-11-30T21:53:54ZengMDPI AGPharmaceuticals1424-82472022-02-0115328010.3390/ph15030280Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization InhibitorsMd. Jahangir Alam0Ozair Alam1Ahmad Perwez2Moshahid Alam Rizvi3Mohd Javed Naim4Vegi G. M. Naidu5Mohd Imran6Mohammed M. Ghoneim7Sultan Alshehri8Faiyaz Shakeel9Medicinal Chemistry and Molecular Modeling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaMedicinal Chemistry and Molecular Modeling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaGenome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110020, IndiaGenome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110020, IndiaMedicinal Chemistry and Molecular Modeling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaNational Institute of Pharmaceutical Education and Research, Guwahati 781101, IndiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi ArabiaDepartment of Pharmacy Practice, College of Pharmacy, Al-Maarefa University, Ad Diriyah 13713, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaSome (<i>E</i>)-3-(3-(4-(benzyloxy)phenyl)-1-phenyl-1<i>H</i>-pyrazol-4-yl)-1-phenylprop-2-en-1-one conjugates <b>5a</b>–<b>r</b> were designed; synthesized; characterized by <sup>1</sup>H, <sup>13</sup>C NMR, and ESI-MS; and evaluated for tubulin polymerization inhibitory activity and in vitro cytotoxicity against breast (MCF-7), cervical (SiHa), and prostate (PC-3) cancer cell lines, as well as a normal cell line (HEK-293T). The compounds were also tested to determine their binding modes at the colchicine-binding site of tubulin protein (PDB ID-3E22), for in silico ADME prediction, for bioactivity study, and for PASS prediction studies. Among all the synthesized conjugates, compound <b>5o</b> exhibited excellent cytotoxicity with an IC<sub>50</sub> value of 2.13 ± 0.80 µM (MCF-7), 4.34 ± 0.98 µM (SiHa), and 4.46 ± 0.53 µM (PC-3) against cancer cell lines. The compound did not exhibit significant toxicity to the HEK cells. Results of the in silico prediction revealed that the majority of the conjugates possessed drug-like properties.https://www.mdpi.com/1424-8247/15/3/280pyrazole conjugateanticancerMTT assaymolecular dockingcytotoxicitytubulin polymerization inhibitors |
| spellingShingle | Md. Jahangir Alam Ozair Alam Ahmad Perwez Moshahid Alam Rizvi Mohd Javed Naim Vegi G. M. Naidu Mohd Imran Mohammed M. Ghoneim Sultan Alshehri Faiyaz Shakeel Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors Pharmaceuticals pyrazole conjugate anticancer MTT assay molecular docking cytotoxicity tubulin polymerization inhibitors |
| title | Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors |
| title_full | Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors |
| title_fullStr | Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors |
| title_full_unstemmed | Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors |
| title_short | Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors |
| title_sort | design synthesis molecular docking and biological evaluation of pyrazole hybrid chalcone conjugates as potential anticancer agents and tubulin polymerization inhibitors |
| topic | pyrazole conjugate anticancer MTT assay molecular docking cytotoxicity tubulin polymerization inhibitors |
| url | https://www.mdpi.com/1424-8247/15/3/280 |
| work_keys_str_mv | AT mdjahangiralam designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT ozairalam designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT ahmadperwez designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT moshahidalamrizvi designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT mohdjavednaim designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT vegigmnaidu designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT mohdimran designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT mohammedmghoneim designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT sultanalshehri designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors AT faiyazshakeel designsynthesismoleculardockingandbiologicalevaluationofpyrazolehybridchalconeconjugatesaspotentialanticanceragentsandtubulinpolymerizationinhibitors |