Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies
Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2171029 |
| _version_ | 1827123360564248576 |
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| author | Faten Farouk Ayman Abo Elmaaty Ahmed Elkamhawy Haytham O. Tawfik Radwan Alnajjar Mohammed A. S. Abourehab Mohamed A. Saleh Wagdy M. Eldehna Ahmed A. Al‐Karmalawy |
| author_facet | Faten Farouk Ayman Abo Elmaaty Ahmed Elkamhawy Haytham O. Tawfik Radwan Alnajjar Mohammed A. S. Abourehab Mohamed A. Saleh Wagdy M. Eldehna Ahmed A. Al‐Karmalawy |
| author_sort | Faten Farouk |
| collection | DOAJ |
| description | Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin (SP) and clarithromycin (CL) showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin (AZ) and CL exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin (ER) and roxithromycin (RO). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics. |
| first_indexed | 2024-03-09T02:03:02Z |
| format | Article |
| id | doaj.art-a1c855bf5ade4c9380cb028408c47807 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:41Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-a1c855bf5ade4c9380cb028408c478072024-09-09T17:23:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2171029Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studiesFaten Farouk0Ayman Abo Elmaaty1Ahmed Elkamhawy2Haytham O. Tawfik3Radwan Alnajjar4Mohammed A. S. Abourehab5Mohamed A. Saleh6Wagdy M. Eldehna7Ahmed A. Al‐Karmalawy8Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said, EgyptBK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of KoreaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, EgyptDepartment of Chemistry, Faculty of Science, University of Benghazi, Benghazi, LibyaDepartment of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, the United Arab EmiratesDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, EgyptTopoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin (SP) and clarithromycin (CL) showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin (AZ) and CL exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin (ER) and roxithromycin (RO). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics.https://www.tandfonline.com/doi/10.1080/14756366.2023.2171029Antibioticscytotoxicitytopoisomerase IImolecular docking and dynamicsMM-GBSA |
| spellingShingle | Faten Farouk Ayman Abo Elmaaty Ahmed Elkamhawy Haytham O. Tawfik Radwan Alnajjar Mohammed A. S. Abourehab Mohamed A. Saleh Wagdy M. Eldehna Ahmed A. Al‐Karmalawy Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies Journal of Enzyme Inhibition and Medicinal Chemistry Antibiotics cytotoxicity topoisomerase II molecular docking and dynamics MM-GBSA |
| title | Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies |
| title_full | Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies |
| title_fullStr | Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies |
| title_full_unstemmed | Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies |
| title_short | Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies |
| title_sort | investigating the potential anticancer activities of antibiotics as topoisomerase ii inhibitors and dna intercalators in vitro molecular docking molecular dynamics and sar studies |
| topic | Antibiotics cytotoxicity topoisomerase II molecular docking and dynamics MM-GBSA |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2171029 |
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