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...
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| author | Pavithren Devakrishnan Nadiah Mad Nasir Johnson Stanslas Muhammad Alif M. Latif Ahmad Zaidi Ismail Fatin Farhana Baharuddin |
| author_facet | Pavithren Devakrishnan Nadiah Mad Nasir Johnson Stanslas Muhammad Alif M. Latif Ahmad Zaidi Ismail Fatin Farhana Baharuddin |
| author_sort | Pavithren Devakrishnan |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-e404732b03214696b6aeea8b051f27cb |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-e404732b03214696b6aeea8b051f27cb2025-01-29T05:00:51ZengElsevierResults in Chemistry2211-71562025-01-0113101998Development and Evaluation of selective nitroxanthone Derivatives: A promising compound for Targeting MCF-7 breast cancer cellsPavithren Devakrishnan0Nadiah Mad Nasir1Johnson Stanslas2Muhammad Alif M. Latif3Ahmad Zaidi Ismail4Fatin Farhana Baharuddin5Department of Chemistry, Faculty of Sciences, University Putra Malaysia, Serdang, Selangor 43400 MalaysiaDepartment of Chemistry, Faculty of Sciences, University Putra Malaysia, Serdang, Selangor 43400 Malaysia; Corresponding author.Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400 MalaysiaCentre of Foundation Studies for Agricultural Science, University Putra Malaysia, Serdang, Selangor 43400 MalaysiaDepartment of Chemistry, Faculty of Sciences, University Putra Malaysia, Serdang, Selangor 43400 MalaysiaDepartment of Chemistry, Faculty of Sciences, University Putra Malaysia, Serdang, Selangor 43400 MalaysiaA 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.http://www.sciencedirect.com/science/article/pii/S2211715624006945NitroxanthoneMCF-7SynthesisMolecular dockingZebrafishBrine shrimp in vitro |
| spellingShingle | Pavithren Devakrishnan Nadiah Mad Nasir Johnson Stanslas Muhammad Alif M. Latif Ahmad Zaidi Ismail Fatin Farhana Baharuddin Development and Evaluation of selective nitroxanthone Derivatives: A promising compound for Targeting MCF-7 breast cancer cells Results in Chemistry Nitroxanthone MCF-7 Synthesis Molecular docking Zebrafish Brine shrimp in vitro |
| 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 |
| topic | Nitroxanthone MCF-7 Synthesis Molecular docking Zebrafish Brine shrimp in vitro |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006945 |
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