戊烷脒
戊烷脒 用途与合成方法
戊烷脒在体外有杀利什曼原虫作用，在体内效果不如五价锑剂。其杀原虫原理可能系干扰敏感原虫的糖酵解。口服胃肠道吸收差，肌注吸收完全，并很快分布于各组织，血药浓度维持时间短暂，但在肝、肾组织中保留时间可达数日。可通过胎盘，但不进乳汁。 戊烷脒用于锑剂治疗无效及不宜用锑剂治疗的黑热病的患者、对锑剂过敏者或治疗中有粒细胞减少者。
不良反应大，如胃部灼感、恶心、呕吐、头痛、头昏、腹痛、心悸等。偶见皮肤瘙痒、黄疸、气促、血压下降等，也可引起低血糖或高血糖。在治疗早期有发热和脾脏增大等。由于刺激作用注射部位出现硬结与血肿。
1.因可使原有的肺结核病灶恶化，故肺结核患者禁用。
2.本品水溶液不稳定，临用时应新鲜配制，并注意避光。肌注前可用灭菌注射用水配成4%～10%溶液。
3.剂量增至每次5～6mg/kg，14～16日为一疗程，治愈率可提高。
IC50: 2.5 μM (
Leishmania infantum
)
Protein tyrosine phosphatases (PTPases)
Phosphatase of regenerating liver (PRL)
Pentamidine (0-10 µg/mL; 6 days; WM9, DU145, C4-2, Hey, WM480, and A549 cells) treatment inhibits the growth of cancer cells in a concentration-dependent manner.
The cytotoxic properties of Pentamidine isethionate towards the promastigotes of the protozoan parasite
Leishmania infantum
is determined. The leishmanicidal activity of Pentamidine isethionate is 60 times higher after 72 h of incubation than that of Cisplatin. Pentamidine isethionate induces a higher amount of programmed cell death (PCD) than Cisplatin, which is associated with inhibition of DNA synthesis and cell-cycle arrest in the G2/M phase. Binding of Pentamidine isethionate to calf-thymus DNA (CT-DNA) induces conformational changes in the DNA double helix, consistent with a B-->A transition. The interaction of Pentamidine isethionate with ubiquitin leads to a 6% increase in the beta-sheet content of the protein.
Cell Viability Assay
| Cell Line: | WM9, DU145, C4-2, Hey, WM480, and A549 cells |
| Concentration: | 0-10 µg/mL |
| Incubation Time: | 6 days |
| Result: | The growth of all six of the cell lines in culture was inhibited in a concentration-dependent manner with complete growth inhibition of the cell lines occurring at 10 µg/mL. |
Pentamidine (0.25 mg/mouse; intramuscular injection; every 2 days; for 4 weeks; athymic nude mice) treatment markedly inhibits the growth of WM9 human melanoma tumors in nude mice.
| Animal Model: | Athymic nude mice (6 weeks old) injected with WM9 cells |
| Dosage: | 0.25 mg/mouse |
| Administration: | Intramuscular injection; every 2 days; for 4 weeks |
| Result: | Markedly inhibited the growth of WM9 human melanoma tumors in nude mice. |
