Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells
A series of nitroxanthone derivatives (1–6) were synthesized and evaluated for their potential efficacy against estrogen-receptor positive (MCF-7) and triple-negative breast cancer cell lines (MDA-MB-231). Cell viability assays identified compound 1 at 10 µM as the most promising candidate due to it...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier B.V.
2025
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| Online Access: | http://psasir.upm.edu.my/id/eprint/115898/ http://psasir.upm.edu.my/id/eprint/115898/1/115898.pdf |
| _version_ | 1848866884106059776 |
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| author | Devakrishnan, Pavithren Mad Nasir, Nadiah Stanslas, Johnson M. Latif, Muhammad Alif Ismail, Ahmad Zaidi Baharuddin, Fatin Farhana |
| author_facet | Devakrishnan, Pavithren Mad Nasir, Nadiah Stanslas, Johnson M. Latif, Muhammad Alif Ismail, Ahmad Zaidi Baharuddin, Fatin Farhana |
| author_sort | Devakrishnan, Pavithren |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | A series of nitroxanthone derivatives (1–6) were synthesized and evaluated for their potential efficacy against estrogen-receptor positive (MCF-7) and triple-negative breast cancer cell lines (MDA-MB-231). Cell viability assays identified compound 1 at 10 µM as the most promising candidate due to its potent growth inhibitory activity (22.05 ± 2.40 %) against the MCF-7 cell line. The half-maximal inhibitory concentration (IC50) of compound 1 was 7.00 ± 0.00 µM for MCF-7 cells, compared to 250.00 ± 70.71 µM for HaCaT and 800.00 ± 0.00 µM for RAW 264.7 cells, yielding selectivity indices (SI) of 35.71 and 114.29, respectively. Additionally, compound 1 exhibited mortality concentrations of 1736.58 µM and 3660.35 µM for zebrafish and brine shrimp embryos, with SI values of 522.91 and 248.08, respectively. Molecular docking analysis showed that compound 1 binds more efficiently to the target enzyme aromatase compared to other derivatives, likely due to its optimal number of nitro groups, orientations, and polarizabilities. Crystal structure analysis revealed that compound 1 crystallizes in the monoclinic system with the C2/c space group. In summary, compound 1 demonstrates selective toxicity towards tumor cells (MCF-7) while being non-toxic to normal cell lines (HaCaT and RAW 264.7) and in vivo studies with brine shrimp and zebrafish. These findings suggest that compound 1 holds promise as a lead compound to target breast cancer cells. |
| first_indexed | 2025-11-15T14:27:41Z |
| format | Article |
| id | upm-115898 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:27:41Z |
| publishDate | 2025 |
| publisher | Elsevier B.V. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1158982025-03-14T00:03:08Z http://psasir.upm.edu.my/id/eprint/115898/ Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells Devakrishnan, Pavithren Mad Nasir, Nadiah Stanslas, Johnson M. Latif, Muhammad Alif Ismail, Ahmad Zaidi Baharuddin, Fatin Farhana A series of nitroxanthone derivatives (1–6) were synthesized and evaluated for their potential efficacy against estrogen-receptor positive (MCF-7) and triple-negative breast cancer cell lines (MDA-MB-231). Cell viability assays identified compound 1 at 10 µM as the most promising candidate due to its potent growth inhibitory activity (22.05 ± 2.40 %) against the MCF-7 cell line. The half-maximal inhibitory concentration (IC50) of compound 1 was 7.00 ± 0.00 µM for MCF-7 cells, compared to 250.00 ± 70.71 µM for HaCaT and 800.00 ± 0.00 µM for RAW 264.7 cells, yielding selectivity indices (SI) of 35.71 and 114.29, respectively. Additionally, compound 1 exhibited mortality concentrations of 1736.58 µM and 3660.35 µM for zebrafish and brine shrimp embryos, with SI values of 522.91 and 248.08, respectively. Molecular docking analysis showed that compound 1 binds more efficiently to the target enzyme aromatase compared to other derivatives, likely due to its optimal number of nitro groups, orientations, and polarizabilities. Crystal structure analysis revealed that compound 1 crystallizes in the monoclinic system with the C2/c space group. In summary, compound 1 demonstrates selective toxicity towards tumor cells (MCF-7) while being non-toxic to normal cell lines (HaCaT and RAW 264.7) and in vivo studies with brine shrimp and zebrafish. These findings suggest that compound 1 holds promise as a lead compound to target breast cancer cells. Elsevier B.V. 2025 Article PeerReviewed text en cc_by_nc_nd_4 http://psasir.upm.edu.my/id/eprint/115898/1/115898.pdf Devakrishnan, Pavithren and Mad Nasir, Nadiah and Stanslas, Johnson and M. Latif, Muhammad Alif and Ismail, Ahmad Zaidi and Baharuddin, Fatin Farhana (2025) Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells. Results in Chemistry, 13. art. no. 101998. pp. 1-15. ISSN 2211-7156; eISSN: 2211-7156 https://linkinghub.elsevier.com/retrieve/pii/S2211715624006945 10.1016/j.rechem.2024.101998 |
| spellingShingle | Devakrishnan, Pavithren Mad Nasir, Nadiah Stanslas, Johnson M. Latif, Muhammad Alif Ismail, Ahmad Zaidi Baharuddin, Fatin Farhana Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title | Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title_full | Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title_fullStr | Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title_full_unstemmed | Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title_short | Development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting MCF-7 breast cancer cells |
| title_sort | development and evaluation of selective nitroxanthone derivatives: a promising compound for targeting mcf-7 breast cancer cells |
| url | http://psasir.upm.edu.my/id/eprint/115898/ http://psasir.upm.edu.my/id/eprint/115898/ http://psasir.upm.edu.my/id/eprint/115898/ http://psasir.upm.edu.my/id/eprint/115898/1/115898.pdf |