Synthesis and biological activity of NOSH-naproxen (AVT-219) and NOSH-sulindac (AVT-18A) as potent anti-inflammatory agents with chemotherapeutic potential.
Synthesis and biological activity of NOSH-naproxen (AVT-219) and NOSH-sulindac (AVT-18A) as potent anti-inflammatory agents with chemotherapeutic potential.
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作者：
Kodela R;Chattopadhyay M;Kashfi K
合成了释放一氧化氮（NO）和硫化氢（H2S）的纳洛芬（NOSH-napolyen）和释放NO和H2S的舒林酸（NOSH-sulinac），并在四种不同的人癌细胞系中评价了它们的细胞生长抑制特性。这些细胞系是腺瘤（结肠、胰腺）、上皮（乳腺）和淋巴细胞（白血病）来源的。使用HT-29人结肠癌细胞，NOSH-nauseen和NOSH-sulinac增加凋亡，并抑制增殖。NOSH-纳洛酮引起G 0/G1期阻滞，而NOSH-舒林酸引起G2/M期阻滞。使用角叉菜胶大鼠足水肿模型，两种化合物均表现出显著的抗炎特性。重建和结构活性的研究代表了一个相当接近的完整的分子表明，NOSH-napolysen是约8000倍，更有效的抑制细胞生长的各部分的总和。我们的数据表明，这些化合物值得进一步研究作为潜在的抗癌剂。
Nitric oxide- (NO) and hydrogen sulfide- (H2S) releasing naproxen (NOSH-naproxen) and NO and H2S-releasing sulindac (NOSH-sulindac) were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. These cell lines are of adenomatous (colon, pancreas), epithelial (breast), and lymphocytic (leukemia) origin. Using HT-29 human colon cancer cells, NOSH-naproxen and NOSH-sulindac increased apoptosis, and inhibited proliferation. NOSH-naproxen caused a G0/G1 whereas NOSH-sulindac caused a G2/M block in the cell cycle. Both compounds exhibited significant anti-inflammatory properties, using the carrageenan rat paw edema model. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-naproxen was approximately 8000-fold more potent than the sum of its parts in inhibiting cell growth. Our data suggest that these compounds merit further investigation as potential anti-cancer agents.