顺铂仍然是 NSCLC 无可争议的标准疗法。然而，由于耐药性和氧化应激引起的毒性，它并不能完全治愈。耐药性与基质金属蛋白酶 (MMP) 的过度表达和异常的钙信号传导有关。我们报道了新型噻唑-三唑杂化物的合成，作为 MMP-9 抑制剂，具有 T 型钙通道阻断和抗氧化作用，使 NSCLC 对顺铂敏感并改善其毒性。 MTT 和全细胞膜片钳分析显示，6d 具有平衡的细胞毒性（IC50 = 21 ±1 nM，SI = 12.14）和 T 型钙通道阻断活性（10 μM 时⁓60%）。它表现出中等的 ROS 清除活性和纳摩尔 MMP-9 抑制 (IC50 = 90 ± 7 nM) 超过 NNGH，MMP-9 超过 -2，MMP-10 超过 -13 选择性。对接和MDs模拟了其受体结合模式。联合研究证实，6d 与顺铂有协同作用（CI = 0.69±0.05），使其 IC50 降低 6.89 倍。总体而言，该研究为非小细胞肺癌铂类治疗引入了潜在的先导佐剂。

Cisplatin remains the unchallenged standard therapy for NSCLC. However, it is not completely curative due to drug resistance and oxidative stress-induced toxicity. Drug resistance is linked to overexpression of matrix metalloproteinases (MMPs) and aberrant calcium signalling. We report synthesis of novel thiazole-triazole hybrids as MMP-9 inhibitors with T-type calcium channel blocking and antioxidant effects to sensitise NSCLC to cisplatin and ameliorate its toxicity. MTT and whole cell patch clamp assays revealed that 6d has a balanced profile of cytotoxicity (IC50 = 21 ± 1 nM, SI = 12.14) and T-type calcium channel blocking activity (⁓60% at 10 μM). It exhibited moderate ROS scavenging activity and nanomolar MMP-9 inhibition (IC50 = 90 ± 7 nM) surpassing NNGH with MMP-9 over -2 and MMP-10 over -13 selectivity. Docking and MDs simulated its receptor binding mode. Combination studies confirmed that 6d synergized with cisplatin (CI = 0.69 ± 0.05) lowering its IC50 by 6.89 folds. Overall, the study introduces potential lead adjuvants for NSCLC platinum-based therapy.