Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents
A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzy...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Journal of Saudi Chemical Society |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610323000029 |
| _version_ | 1797861172349763584 |
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| author | Rajapandi Raju Kumarappan Chidambaram Balakumar Chandrasekaran Mohammad F. Bayan Tapan Kumar Maity Abdullah M. Alkahtani Harish C Chandramoorthy |
| author_facet | Rajapandi Raju Kumarappan Chidambaram Balakumar Chandrasekaran Mohammad F. Bayan Tapan Kumar Maity Abdullah M. Alkahtani Harish C Chandramoorthy |
| author_sort | Rajapandi Raju |
| collection | DOAJ |
| description | A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N4 piperazine was found to be the most active with the promising IC50 (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery. |
| first_indexed | 2024-04-09T21:57:48Z |
| format | Article |
| id | doaj.art-bac5222bdfee4892997a7bcb04780389 |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-04-09T21:57:48Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-bac5222bdfee4892997a7bcb047803892023-03-24T04:22:06ZengElsevierJournal of Saudi Chemical Society1319-61032023-03-01272101598Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agentsRajapandi Raju0Kumarappan Chidambaram1Balakumar Chandrasekaran2Mohammad F. Bayan3Tapan Kumar Maity4Abdullah M. Alkahtani5Harish C Chandramoorthy6Department of Pharmaceutical Chemistry, Arulmigu Kalasalingam College of Pharmacy, Krishnankovil- 626126, Tamilnadu, India; Corresponding authors.Department of Pharmacology, College of Pharmacy, King Khalid University, P. O. Box: 960, Abha 61421, Saudi Arabia; Corresponding authors.Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman, 19392, JordanFaculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman, 19392, JordanDepartment of Pharmaceutical Technology, Division of Pharmaceutical Chemistry, Jadavpur University, Kolkata 700032, IndiaDepartment of Microbiology & Clinical Parasitology, College of Medicine, King Khalid, University, Al-Qara, Saudi ArabiaDepartment of Microbiology & Clinical Parasitology, College of Medicine, King Khalid, University, Al-Qara, Saudi Arabia; Center for Stem Cell Research, College of Medicine, King Khalid University, Al-Qara, Saudi ArabiaA novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N4 piperazine was found to be the most active with the promising IC50 (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery.http://www.sciencedirect.com/science/article/pii/S1319610323000029Isatin-pyrimidine hybridAntiproliferative activityBreast cancer cell (MCF-7)Dalton’s ascitic lymphoma (DAL)Molecular docking |
| spellingShingle | Rajapandi Raju Kumarappan Chidambaram Balakumar Chandrasekaran Mohammad F. Bayan Tapan Kumar Maity Abdullah M. Alkahtani Harish C Chandramoorthy Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents Journal of Saudi Chemical Society Isatin-pyrimidine hybrid Antiproliferative activity Breast cancer cell (MCF-7) Dalton’s ascitic lymphoma (DAL) Molecular docking |
| title | Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| title_full | Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| title_fullStr | Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| title_full_unstemmed | Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| title_short | Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| title_sort | synthesis pharmacological evaluation and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
| topic | Isatin-pyrimidine hybrid Antiproliferative activity Breast cancer cell (MCF-7) Dalton’s ascitic lymphoma (DAL) Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S1319610323000029 |
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