New Ru(III) NAMI/NAMI-A Analogue Complexes with Selective Anticancer Activity.

NAMI-A (ImH)[trans-RuCl4(dmso-S)(Im)], where dmso-S = sulfur-bonded dimethyl sulfoxide and Im = imidazole emerged as a promising alternative to approved Pt(II) anticancer drugs, offering high antimetastatic activity and low toxicity. However, its development was discontinued due to insufficient activity against primary tumors. In this work, we synthesized 12 new pyridine NAMI derivatives and evaluated their anticancer activity against three cancer cell lines: lung adenocarcinoma A549, melanoma MeWo and bladder cancer T24, and compared with the nonmalignant keratinocyte HaCaT cells. Among them, two complexes exhibited potent cytotoxicity and selectivity while retaining the characteristic antimetastatic activity of the NAMI scaffold. The Ru(III) complex (CHO-PyH)[trans-Ru(CHO-Py)Cl4 (dmso-S)], where CHO-Py = pyridine-3-aldehyde, displayed an IC50 of 34 μM and a selectivity index of 7.60 against A549 cells. Additionally, (NCS-PyH)[trans-RuCl4(dmso-S)(NCS-Py)], where NCS-Py = 3-(isothiocyanatomethyl)pyridine, showed an IC50 of 240 nM and a selectivity index of 5.2 against T24 cells.