Computational identification of potential inhibitors targeting cdk1 in colorectal cancer
Introduction: Despite improved treatment options, colorectal cancer (CRC) remains a huge public health concern with a significant impact on affected individuals. Cell cycle dysregulation and overexpression of certain regulators and checkpoint activators are important recurring events in the progress...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1264808/full |
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| author | Uchechukwu C. Ogbodo Ojochenemi A. Enejoh Chinelo H. Okonkwo Pranavathiyani Gnanasekar Pauline W. Gachanja Shamim Osata Halimat C. Atanda Emmanuel A. Iwuchukwu Ikechukwu Achilonu Olaitan I. Awe Olaitan I. Awe |
| author_facet | Uchechukwu C. Ogbodo Ojochenemi A. Enejoh Chinelo H. Okonkwo Pranavathiyani Gnanasekar Pauline W. Gachanja Shamim Osata Halimat C. Atanda Emmanuel A. Iwuchukwu Ikechukwu Achilonu Olaitan I. Awe Olaitan I. Awe |
| author_sort | Uchechukwu C. Ogbodo |
| collection | DOAJ |
| description | Introduction: Despite improved treatment options, colorectal cancer (CRC) remains a huge public health concern with a significant impact on affected individuals. Cell cycle dysregulation and overexpression of certain regulators and checkpoint activators are important recurring events in the progression of cancer. Cyclin-dependent kinase 1 (CDK1), a key regulator of the cell cycle component central to the uncontrolled proliferation of malignant cells, has been reportedly implicated in CRC. This study aimed to identify CDK1 inhibitors with potential for clinical drug research in CRC.Methods: Ten thousand (10,000) naturally occurring compounds were evaluated for their inhibitory efficacies against CDK1 through molecular docking studies. The stability of the lead compounds in complex with CDK1 was evaluated using molecular dynamics simulation for one thousand (1,000) nanoseconds. The top-scoring candidates’ ADME characteristics and drug-likeness were profiled using SwissADME.Results: Four hit compounds, namely, spiraeoside, robinetin, 6-hydroxyluteolin, and quercetagetin were identified from molecular docking analysis to possess the least binding scores. Molecular dynamics simulation revealed that robinetin and 6-hydroxyluteolin complexes were stable within the binding pocket of the CDK1 protein.Discussion: The findings from this study provide insight into novel candidates with specific inhibitory CDK1 activities that can be further investigated through animal testing, clinical trials, and drug development research for CRC treatment. |
| first_indexed | 2024-03-09T14:02:18Z |
| format | Article |
| id | doaj.art-cbb31e45095f490c8bd27b27a8c27c35 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-09T14:02:18Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-cbb31e45095f490c8bd27b27a8c27c352023-11-30T07:20:26ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-11-011110.3389/fchem.2023.12648081264808Computational identification of potential inhibitors targeting cdk1 in colorectal cancerUchechukwu C. Ogbodo0Ojochenemi A. Enejoh1Chinelo H. Okonkwo2Pranavathiyani Gnanasekar3Pauline W. Gachanja4Shamim Osata5Halimat C. Atanda6Emmanuel A. Iwuchukwu7Ikechukwu Achilonu8Olaitan I. Awe9Olaitan I. Awe10Department of Applied Biochemistry, Nnamdi Azikiwe University, Awka, NigeriaGenomics and Bioinformatics Department, National Biotechnology Development Agency, Abuja, NigeriaDepartment of Pharmacology and Toxicology, University of Nigeria, Nsukka, NigeriaDepartment of Bioinformatics, Pondicherry University, Puducherry, IndiaDepartment of Biochemistry and Biotechnology, Pwani University, Kilifi, KenyaDepartment of Biochemistry, University of Nairobi, Nairobi, KenyaBiotechnology Department, Federal University of Technology, Akure, NigeriaProtein Structure-Function Research Unit, School of Molecular and Cell Biology, Faculty of Sciences, University of Witwatersrand, Johannesburg, South AfricaProtein Structure-Function Research Unit, School of Molecular and Cell Biology, Faculty of Sciences, University of Witwatersrand, Johannesburg, South AfricaDepartment of Computer Science, University of Ibadan, Ibadan, Nigeria0African Society for Bioinformatics and Computational Biology, Cape Town, South AfricaIntroduction: Despite improved treatment options, colorectal cancer (CRC) remains a huge public health concern with a significant impact on affected individuals. Cell cycle dysregulation and overexpression of certain regulators and checkpoint activators are important recurring events in the progression of cancer. Cyclin-dependent kinase 1 (CDK1), a key regulator of the cell cycle component central to the uncontrolled proliferation of malignant cells, has been reportedly implicated in CRC. This study aimed to identify CDK1 inhibitors with potential for clinical drug research in CRC.Methods: Ten thousand (10,000) naturally occurring compounds were evaluated for their inhibitory efficacies against CDK1 through molecular docking studies. The stability of the lead compounds in complex with CDK1 was evaluated using molecular dynamics simulation for one thousand (1,000) nanoseconds. The top-scoring candidates’ ADME characteristics and drug-likeness were profiled using SwissADME.Results: Four hit compounds, namely, spiraeoside, robinetin, 6-hydroxyluteolin, and quercetagetin were identified from molecular docking analysis to possess the least binding scores. Molecular dynamics simulation revealed that robinetin and 6-hydroxyluteolin complexes were stable within the binding pocket of the CDK1 protein.Discussion: The findings from this study provide insight into novel candidates with specific inhibitory CDK1 activities that can be further investigated through animal testing, clinical trials, and drug development research for CRC treatment.https://www.frontiersin.org/articles/10.3389/fchem.2023.1264808/fullcolorectal cancercyclin-dependent kinase 1inhibitorsnatural compoundsmolecular dynamics simulation |
| spellingShingle | Uchechukwu C. Ogbodo Ojochenemi A. Enejoh Chinelo H. Okonkwo Pranavathiyani Gnanasekar Pauline W. Gachanja Shamim Osata Halimat C. Atanda Emmanuel A. Iwuchukwu Ikechukwu Achilonu Olaitan I. Awe Olaitan I. Awe Computational identification of potential inhibitors targeting cdk1 in colorectal cancer Frontiers in Chemistry colorectal cancer cyclin-dependent kinase 1 inhibitors natural compounds molecular dynamics simulation |
| title | Computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| title_full | Computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| title_fullStr | Computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| title_full_unstemmed | Computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| title_short | Computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| title_sort | computational identification of potential inhibitors targeting cdk1 in colorectal cancer |
| topic | colorectal cancer cyclin-dependent kinase 1 inhibitors natural compounds molecular dynamics simulation |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1264808/full |
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