Amaro María I, Monasterios Melina, Avendaño Milagros, Charris Jaime
Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela. Apartado 40-109, Caracas 1040 A, Venezuela.
J Appl Toxicol. 2009 Jan;29(1):36-41. doi: 10.1002/jat.1379.
This study describes the preliminary toxicity evaluation of five new furan derivatives, 2-[2-acetylamino-2-[(benzothiazolyl-substituted)aminocarbonyl]vinyl]-5-nitro furane (compounds A, B, D and E) and 2-[2-phenylamino-2-[benzothiazolylaminocarbonyl]vinyl]furane (compound C). Cytotoxicity was determined using the MTT (tetrazolium salt) method over BHK21 (Syrian baby hamster kidney) and Hep-2 (human larynx carcinoma) cells, which had previously been used to evaluate the cytotoxicity of the 5-nitrofuran derivatives. The lethal concentration 50 (LC(50)) was determined using brine shrimp (Artemia salina) bioassay. Nitrofurantoin was used as reference compound. The results demonstrate that BHK21 cells are more sensitive than Hep-2 cells. This structurally related serial of compounds shows a differential toxicity, which is an indication that the toxicity naturally arising from the nitro group can be modulated by the substituents over the furan ring. Additionally, compound C, the only derivative with no nitro group, was least toxic to Hep-2, but exhibits toxicity to BHK21 cells and brine shrimp. The LC(50 )brine shrimp test (BST) bioassay results were as follows: A, 654.2 microg ml(-1); B, 50.0 microg ml(-1); C, 533.4 microg ml(-1); D, 172.1 microg ml(-1); E, 76.4 microg ml(-1), and NF, >1000 microg ml(-1).
本研究描述了5种新型呋喃衍生物，即2-[2-乙酰氨基-2-[(苯并噻唑基取代的)氨基羰基]乙烯基]-5-硝基呋喃（化合物A、B、D和E）以及2-[2-苯氨基-2-[苯并噻唑基氨基羰基]乙烯基]呋喃（化合物C）的初步毒性评估。采用MTT（四唑盐）法测定了BHK21（叙利亚仓鼠肾细胞）和Hep-2（人喉癌细胞）的细胞毒性，这两种细胞先前已用于评估5-硝基呋喃衍生物的细胞毒性。使用卤虫（卤虫）生物测定法测定致死浓度50（LC(50)）。呋喃妥因用作参考化合物。结果表明，BHK21细胞比Hep-2细胞更敏感。这一系列结构相关的化合物表现出不同的毒性，这表明呋喃环上的取代基可以调节硝基天然产生的毒性。此外，化合物C是唯一不含硝基的衍生物，对Hep-2的毒性最小，但对BHK21细胞和卤虫表现出毒性。卤虫试验（BST）生物测定法的LC(50)结果如下：A，654.2微克/毫升；B，50.0微克/毫升；C，533.4微克/毫升；D，172.1微克/毫升；E，76.4微克/毫升，以及NF，>1000微克/毫升。
