Discovery of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agents: virtual screening and molecular dynamic studies

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dc.authoridAlmehizia, Abdulrahman/0000-0001-8711-3873
dc.authoridGupta, Shankar/0000-0003-3393-6465
dc.contributor.authorDhiman, S.
dc.contributor.authorGupta, S.
dc.contributor.authorKashaw, S. K.
dc.contributor.authorChtita, S.
dc.contributor.authorKaya, S.
dc.contributor.authorAlmehizia, A. A.
dc.contributor.authorAsati, V.
dc.date.accessioned2025-05-04T16:46:55Z
dc.date.available2025-05-04T16:46:55Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractCDK/Cyclins are dysregulated in several human cancers. Recent studies showed inhibition of CDK4/6 was responsible for controlling cell cycle progression and cancer cell growth. In the present study, atom-based and field-based 3D-QSAR, virtual screening, molecular docking and molecular dynamics studies were done for the development of novel pyrrolo[2,3-d]pyrimidine (P2P) derivatives as anticancer agents. The developed models showed good Q2 and r2 values for atom-based 3D-QSAR, which were equal to 0.7327 and 0.8939, whereas for field-based 3D-QSAR the values were 0.8552 and 0.6255, respectively. Molecular docking study showed good-binding interactions with amino acid residues such as VAL-101, HIE-100, ASP-104, ILE-19, LYS-147 and GLU-99, important for CDK4/6 inhibitory activity by using PDB ID: 5L2S. Pharmacophore hypothesis (HHHRR_1) was used in the screening of ZINC database. The top scored ZINC compound ZINC91325512 showed binding interactions with amino acid residues VAL-101, ILE-19, and LYS-147. Enumeration study revealed that the screened compound R1 showed binding interactions with VAL 101 and GLN 149 residues. Furthermore, the Molecular dynamic study showed compound R1, ZINC91325512 and ZINC04000264 having RMSD values of 1.649, 1.733 and 1.610 & Aring;, respectively. These ZINC and enumerated compounds may be used for the development of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agent.
dc.description.sponsorshipKing Saud University [RSPD2024R852]; King Saud University, Riyadh, Saudi Arabia; ISF College of Pharmacy; DST-FIST Lab
dc.description.sponsorshipThe authors are grateful to King Saud University, Riyadh, Saudi Arabia, for funding the work through the Researchers Supporting Project No. (RSPD2024R852). We thank ISF College of Pharmacy, Moga, and DST-FIST Lab, ISFCP for providing facilities for this research work.
dc.identifier.doi10.1080/1062936X.2024.2432009
dc.identifier.endpage1025
dc.identifier.issn1062-936X
dc.identifier.issn1029-046X
dc.identifier.issue11
dc.identifier.pmid39607421
dc.identifier.scopus2-s2.0-85210589083
dc.identifier.scopusqualityQ2
dc.identifier.startpage993
dc.identifier.urihttps://doi.org/10.1080/1062936X.2024.2432009
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35406
dc.identifier.volume35
dc.identifier.wosWOS:001365793100001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofSar and Qsar in Environmental Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectCDK4 inhibitors
dc.subject3D-QSAR
dc.subjectpharmacophore mapping
dc.subjectvirtual screening
dc.subjectmolecular dynamics simulation
dc.titleDiscovery of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agents: virtual screening and molecular dynamic studies
dc.typeArticle

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