研究人員將兩種阿司匹林衍生物結(jié)合在一起形成一種新的雜合物，在實驗室測試中,，它似乎比其中任何一種衍生物更加有效地控制幾種類型癌癥的生長,。他們在ACS Medicinal Chemistry Letters期刊上報道了這種新的雜合物NOSH-阿司匹林(NOSH-aspirin),，如此命名是因為它釋放一氧化氮(NO)和硫化氫(H2S)。
研究人員Khosrow Kashfi,、Ravinder Kodela和Mitali Chattopadhyay指出NO和H2S是該雜合物產(chǎn)生的兩種信號傳導(dǎo)物質(zhì),，能夠松弛血管，減輕炎癥和產(chǎn)生多種其他效應(yīng),?？茖W(xué)家之前為了減輕阿司匹林潛在性地導(dǎo)致胃腸道出血的副作用而開發(fā)出一種能夠釋放NO的阿司匹林衍生物(NO-aspirin)?？茖W(xué)家之前也開發(fā)出另一種能夠釋放H2S的阿司匹林衍生物(H2S-aspirin),，它有抗炎癥性質(zhì)而且似乎不對胃部帶來傷害。
因為NO和H2S是有著生理重要意義的氣體,，而且Kashfi領(lǐng)導(dǎo)的研究小組之前證實NO-aspirin和H2S-aspirin確實有良好效果,，所以他們推測將這兩種化合物整合在一起的新雜合物可能比它們當(dāng)中的任何一種都要更加強有力和有效。經(jīng)實驗證實他們的假設(shè)確實是對的,。
他們在實驗室測試中發(fā)現(xiàn)這種新的雜合物抑制乳腺癌,、結(jié)腸癌、胰腺癌,、肺癌,、前列腺癌和一些白血病癌細(xì)胞生長。經(jīng)測試,，一些NOSH-aspirin要比阿司匹林單獨抵抗癌細(xì)胞生長的能力強10萬多倍,。更有希望的是，研究小組報道他們開發(fā)的雜合物并不傷害正常細(xì)胞,。(生物谷：towersimper編譯)
doi:10.1021/ml300002m
PMC:
PMID:
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.
