研究人员将两种阿司匹林衍生物结合在一起形成一种新的杂合物，在实验室测试中，它似乎比其中任何一种衍生物更加有效地控制几种类型癌症的生长。他们在ACS Medicinal Chemistry Letters期刊上报道了这种新的杂合物NOSH-阿司匹林(NOSH-aspirin)，如此命名是因为它释放一氧化氮(NO)和硫化氢(H2S)。
研究人员Khosrow Kashfi、Ravinder Kodela和Mitali Chattopadhyay指出NO和H2S是该杂合物产生的两种信号传导物质，能够松弛血管，减轻炎症和产生多种其他效应。科学家之前为了减轻阿司匹林潜在性地导致胃肠道出血的副作用而开发出一种能够释放NO的阿司匹林衍生物(NO-aspirin)。科学家之前也开发出另一种能够释放H2S的阿司匹林衍生物(H2S-aspirin)，它有抗炎症性质而且似乎不对胃部带来伤害。
因为NO和H2S是有着生理重要意义的气体，而且Kashfi领导的研究小组之前证实NO-aspirin和H2S-aspirin确实有良好效果，所以他们推测将这两种化合物整合在一起的新杂合物可能比它们当中的任何一种都要更加强有力和有效。经实验证实他们的假设确实是对的。
他们在实验室测试中发现这种新的杂合物抑制乳腺癌、结肠癌、胰腺癌、肺癌、前列腺癌和一些白血病癌细胞生长。经测试，一些NOSH-aspirin要比阿司匹林单独抵抗癌细胞生长的能力强10万多倍。更有希望的是，研究小组报道他们开发的杂合物并不伤害正常细胞。(生物谷：towersimper编译)
doi:10.1021/ml300002m
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NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals
Ravinder Kodela, Mitali Chattopadhyay, and Khosrow Kashfi
A series of new hybrids of aspirin (ASA), bearing both nitric oxide (NO) and hydrogen sulfide (H2S)-releasing moieties were synthesized and designated as NOSH compounds (1–4). NOSH-1 (4-(3-thioxo-3H-1,2-dithiol-5-yl) phenyl 2-((4-(nitrooxy)butanoyl)oxy) benzoate); NOSH-2 (4-(nitrooxy)butyl (2-((4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)carbonyl)phenyl)); NOSH-3 (4-carbamothioylphenyl 2-((4-(nitrooxy)butanoyl)oxy)benzoate); and NOSH-4 (4-(nitrooxy)butyl 2-(5-((R )-1,2-dithiolan-3-yl)pentanoyloxy)benzoate). The cell growth inhibitory properties of compounds 1–4 were evaluated in eleven different human cancer cell lines of six different tissue origins. These cell lines are of adenomatous (colon, pancreatic, lung, prostate), epithelial (breast), and lymphocytic (leukemia) origin. All NOSH compounds were extremely effective in inhibiting the growth of these cell lines. NOSH-1 was the most potent, with an IC50 of 48 ± 3 nM in HT-29 colon cancer cells. This is the first NSAID-based compound with such potency. This compound was also devoid of any cellular toxicity, as determined by LDH release. NOSH-1 was comparable to aspirin in its anti-inflammatory properties, using the carrageenan rat paw edema model.
