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New Ru(III) NAMI/NAMI-A Analogue Complexes with Selective Anticancer Activity
Manel Estruch-Blasco1, Jose Manuel Calderón-Montaño2, Eleuterio Álvarez3
1Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, c/Profesor García González, 2, Sevilla 41012, Spain.
Journal of Medicinal Chemistry
|July 23, 2026
Summary
Researchers developed new ruthenium(III) complexes with pyridine ligands, showing potent anticancer activity against lung, melanoma, and bladder cancer cells. These NAMI derivatives offer improved cytotoxicity and selectivity, retaining antimetastatic properties for potential cancer therapy.
Area of Science:
- Medicinal Chemistry
- Inorganic Chemistry
- Cancer Research
Background:
- NAMI-A, a ruthenium(III) complex, demonstrated antimetastatic potential but lacked efficacy against primary tumors.
- Platinum(II) anticancer drugs face limitations, necessitating the development of novel therapeutic agents.
- The NAMI scaffold offers a promising basis for new anticancer drug discovery.
Purpose of the Study:
- To synthesize and evaluate novel pyridine NAMI derivatives as potential anticancer agents.
- To assess the cytotoxicity and selectivity of these derivatives against various cancer cell lines.
- To investigate the retention of antimetastatic activity in the new NAMI derivatives.
Main Methods:
- Synthesis of 12 new pyridine NAMI derivatives.
- Anticancer activity evaluation using lung adenocarcinoma (A549), melanoma (MeWo), and bladder cancer (T24) cell lines.
- Comparison of efficacy against nonmalignant keratinocyte (HaCaT) cells to determine selectivity.
Main Results:
- Two ruthenium(III) complexes exhibited significant cytotoxicity and selectivity.
- The complex (CHO-PyH)[trans-Ru(CHO-Py)Cl4(dmso-S)] showed an IC50 of 34 μM and selectivity index of 7.60 against A549 cells.
- The complex (NCS-PyH)[trans-RuCl4(dmso-S)(NCS-Py)] displayed an IC50 of 240 nM and selectivity index of 5.2 against T24 cells, retaining antimetastatic properties.
Conclusions:
- Novel pyridine NAMI derivatives possess potent anticancer activity and selectivity.
- These compounds represent promising candidates for further development as anticancer therapeutics.
- The findings support the potential of modified NAMI scaffolds in cancer treatment.
