IR-2

Organometallic iridium(III) complexes are a highly promising class of metal-based anticancer agents. In this study, three bis-/tris-heteroleptic iridium(III) complexes-[Ir(piq)₂(bpy)]PF₆ (Ir1), [Ir(piq)(btp)(bpy)]PF₆ (Ir2) and [Ir(btp)₂(bpy)]PF₆ (Ir3)-were synthesized and characterized, where piq = 1-phenylisoquinoline, btp = 2-(benzothienyl)pyridine and bpy = 2,2'-bipyridine. Their photophysical properties were studied, and theoretical calculations were conducted to better understand the variations along the series. All complexes exhibited potent cytotoxicity against tumor cells, among which tris-heteroleptic complex Ir2 showed superior activity toward HeLa cells-prompting comprehensive antitumor studies of this complex. Laser confocal assay revealed that Ir2 entered cells via an energy-dependent uptake mechanism while exhibiting specific mitochondrial targeting, as evidenced by a high Pearson's colocalization coefficient (PCC = 0.93). Subsequent biological assays-including apoptosis analysis, cell cycle arrest, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) changes-revealed that complex Ir2 induced HeLa cells apoptosis through mitochondrial dysfunction. The antitumor activity in vivo confirmed that Ir2 could effectively suppressed tumor growth in HeLa xenograft-bearing mice (61.80 % inhibition) without adverse effects on major organs. Overall, complex Ir2 represents a novel asymmetric tris-heteroleptic iridium(III) complex developed for anticancer applications, with results demonstrating its excellent antitumor efficacy, thereby positioning its potential as a new alternative to conventional anticancer agents.

This study investigates whether 5-min ischemic preconditioning (IR5) more effectively reduces submaximal exercise blood pressure and improves muscle oxygenation compared to 2-min ischemia (IR2) or 2-min isometric priming (IM2).

Twenty untrained men (10 prehypertensive; 10 normotensive) completed, in randomized order, IR5 (3 × 5 min bilateral limb occlusion at 220 mmHg), IR2 (3 × 2 min bilateral occlusion), and IM2 (3 × 2 min 30 % maximal voluntary contraction isometric knee extension), each followed by the submaximal exercise test. Outcomes were exercise heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and vastus lateralis muscle oxygenation including Δdeoxyhemoglobin (ΔHHb), Δtotal hemoglobin (ΔtHb), and Δtissue saturation index (ΔTSI).

IR5 significantly attenuated the submaximal pressor response, reducing SBP by mean difference (MD) = -2.23 mmHg (P < .001, ηp² = 0.395) compared with both IR2 and IM2. A significant Condition × Group interaction (P = .023) indicated that the MAP reduction was confined to prehypertensive participants (MD = -3.14 mmHg, P = .003). During exercise, IR5 increased ΔtHb by MD = 1.56 μmol/L (ηp² = 0.606) and mitigated the decline in ΔTSI by MD = 2.98 % (ηp² = 0.716) without altering ΔHHb. In contrast, IR2 and IM2 elicited similar occlusion-phase deoxygenation but did not modify exercise hemodynamics or oxygenation metrics.

IR5 effectively lowers SBP and MAP during submaximal exercise and improves muscle oxygenation. It is a safe, non-pharmacological pre-exercise strategy to manage blood pressure and potentially reduce cardiovascular risk.