Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking
Novel 1,3,4-thiadiazole-based pyrazolo[3,4-d]pyrimidine derivatives (7a–7 l) were synthesised in this study, and their structures were ascertained utilizing a range of spectroscopic methods, including HREI-MS, IR, and NMR (1H/13C). They showed especially strong activity (IC50 range 1.56–44 μM). With...
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Elsevier
2025-03-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625000761 |
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| author | Peduri Suresh Reddy Thuraka Sekhar Pinnu Thriveni Gandla Mahesh Kumar Allaka Tejeswara Rao Mohammad Raish Tota Giridhar Gudipati Srinivasulu |
| author_facet | Peduri Suresh Reddy Thuraka Sekhar Pinnu Thriveni Gandla Mahesh Kumar Allaka Tejeswara Rao Mohammad Raish Tota Giridhar Gudipati Srinivasulu |
| author_sort | Peduri Suresh Reddy |
| collection | DOAJ |
| description | Novel 1,3,4-thiadiazole-based pyrazolo[3,4-d]pyrimidine derivatives (7a–7 l) were synthesised in this study, and their structures were ascertained utilizing a range of spectroscopic methods, including HREI-MS, IR, and NMR (1H/13C). They showed especially strong activity (IC50 range 1.56–44 μM). With IC50 values of 2.49 ± 1.9, 1.56 ± 1.3, and 2.97 ± 2.6 μM against Caco-2, HCT116, and A549 cell lines, respectively, compound 7f demonstrated the strongest anticancer properties among all synthesised compounds when compared to the conventional medication doxorubicin (IC50 = 3.10 to 3.32 μM). Additionally, the anchoring function of the 1,3,4-thiadiazole-substituted pyrazolo[3,4-d]pyrimidine moiety in interacting with anticancer targets and hydrophobic interaction with the essential amino acid residues has been highlighted by molecular modeling studies. The study shows how certain residues from the colorectal cancer mutant (1WCH) interact with each other in a way that is stable. Furthermore, these compounds intriguing therapeutic potential is highlighted by their favorable drug-likeness and ADME-Tox characteristics, which call for more research into possible clinical applications. These compounds are attractive candidates for further investigation in the search for new therapeutic agents due to their diverse actions, which include anticancer qualities. |
| format | Article |
| id | doaj-art-d4c6bd4f71a9477db8c06db4f2cb0643 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-d4c6bd4f71a9477db8c06db4f2cb06432025-02-09T05:00:06ZengElsevierResults in Chemistry2211-71562025-03-0114102093Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular dockingPeduri Suresh Reddy0Thuraka Sekhar1Pinnu Thriveni2Gandla Mahesh Kumar3Allaka Tejeswara Rao4Mohammad Raish5Tota Giridhar6Gudipati Srinivasulu7Department of Chemistry, Vikram Simhapuri University, Nellore, Andhra Pradesh 524324, India; Research and Development, Shodhana Laboratories Pvt. Ltd., IDA Jeedimetla, Hyderabad, Telangana 500055, IndiaDepartment of Chemistry, Vikram Simhapuri University, Nellore, Andhra Pradesh 524324, IndiaDepartment of Chemistry, Vikram Simhapuri University, Nellore, Andhra Pradesh 524324, India; Corresponding author.Department of Chemistry, National Institute of Technology, Warangal, Telangana 506004, India; Department of Chemistry, Institute of Aeronautical Engineering, Dundigal, Hyderabad, Telangana 500043, IndiaCentre for Chemical Sciences and Technology, University College of Engineering Science and Technology Hyderabad, Jawaharlal Nehru Technological University Hyderabad, Hyderabad 500085, Telangana, IndiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaResearch and Development, Shodhana Laboratories Pvt. Ltd., IDA Jeedimetla, Hyderabad, Telangana 500055, IndiaResearch and Development, Shodhana Laboratories Pvt. Ltd., IDA Jeedimetla, Hyderabad, Telangana 500055, IndiaNovel 1,3,4-thiadiazole-based pyrazolo[3,4-d]pyrimidine derivatives (7a–7 l) were synthesised in this study, and their structures were ascertained utilizing a range of spectroscopic methods, including HREI-MS, IR, and NMR (1H/13C). They showed especially strong activity (IC50 range 1.56–44 μM). With IC50 values of 2.49 ± 1.9, 1.56 ± 1.3, and 2.97 ± 2.6 μM against Caco-2, HCT116, and A549 cell lines, respectively, compound 7f demonstrated the strongest anticancer properties among all synthesised compounds when compared to the conventional medication doxorubicin (IC50 = 3.10 to 3.32 μM). Additionally, the anchoring function of the 1,3,4-thiadiazole-substituted pyrazolo[3,4-d]pyrimidine moiety in interacting with anticancer targets and hydrophobic interaction with the essential amino acid residues has been highlighted by molecular modeling studies. The study shows how certain residues from the colorectal cancer mutant (1WCH) interact with each other in a way that is stable. Furthermore, these compounds intriguing therapeutic potential is highlighted by their favorable drug-likeness and ADME-Tox characteristics, which call for more research into possible clinical applications. These compounds are attractive candidates for further investigation in the search for new therapeutic agents due to their diverse actions, which include anticancer qualities.http://www.sciencedirect.com/science/article/pii/S22117156250007611,3,4-ThiadiazolePyrazolo[3,4-d]pyrimidineAntiproliferative activity1WCH2P85ADME-Tox |
| spellingShingle | Peduri Suresh Reddy Thuraka Sekhar Pinnu Thriveni Gandla Mahesh Kumar Allaka Tejeswara Rao Mohammad Raish Tota Giridhar Gudipati Srinivasulu Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking Results in Chemistry 1,3,4-Thiadiazole Pyrazolo[3,4-d]pyrimidine Antiproliferative activity 1WCH 2P85 ADME-Tox |
| title | Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking |
| title_full | Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking |
| title_fullStr | Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking |
| title_full_unstemmed | Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking |
| title_short | Design, theoretical approaches and new framework of pyrazolo[3,4-d]pyrimidine as potent anticancer agents: Efficient synthesis, ADME-T and molecular docking |
| title_sort | design theoretical approaches and new framework of pyrazolo 3 4 d pyrimidine as potent anticancer agents efficient synthesis adme t and molecular docking |
| topic | 1,3,4-Thiadiazole Pyrazolo[3,4-d]pyrimidine Antiproliferative activity 1WCH 2P85 ADME-Tox |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625000761 |
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