Schraufnagel D E
Department of Medicine, University of Illinois at Chicago, 60612-7323, USA.
Int J Tuberc Lung Dis. 1999 Aug;3(8):651-62.
As we move into the next century it appears that new antituberculosis drugs will arise from four categories: 1) new use of old drugs, 2) new delivery of old drugs, 3) new drugs within old classes, and 4) new classes of drugs. Old drugs such as clofazimine and its analogues, rifabutin, the macrolides, aminoglycosides, quinolones and perhaps vitamin D may find a way into better regimens. New therapy may also arise from new combinations and new uses of current antituberculosis drugs. New drugs are being developed in the rifamycin, fluoroquinolone, and nitroimidazole families. Several immune amplifiers, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and interleukin-12 (IL-12) have undergone pilot testing. Counteracting adhesion molecules is being tested for several infectious diseases. With the unraveling of the tuberculosis genome, attacking enzymes unique to Mycobacterium tuberculosis is easier and allows us to hit elements in both a metabolic pathway and its alternate pathway. Interfering with transcription factors that bind DNA but do not promote RNA production could interrupt transcription. Genetic products of mycobacteria can be modified to cause their own death. Phages may deliver antisense nucleic acids for inhibition of mycobacterial gene expression. The distinction between drugs, immunotherapies and vaccines may blur.
随着我们迈入下个世纪，新的抗结核药物似乎将来自以下四类：1）旧药新用；2）旧药新剂型；3）旧类别中的新药；4）新类别的药物。氯法齐明及其类似物、利福布汀、大环内酯类、氨基糖苷类、喹诺酮类以及或许还有维生素D等旧药可能会找到更好的用药方案。新疗法也可能源自现有抗结核药物的新组合和新用途。利福霉素、氟喹诺酮和硝基咪唑家族正在研发新药。几种免疫增强剂，如γ干扰素（IFN-γ）、白细胞介素-2（IL-2）和白细胞介素-12（IL-12）已经进行了初步试验。针对几种传染病正在测试对抗黏附分子的方法。随着结核分枝杆菌基因组的解析，攻击结核分枝杆菌特有的酶变得更容易，使我们能够针对代谢途径及其替代途径中的成分。干扰与DNA结合但不促进RNA产生的转录因子可能会中断转录。分枝杆菌的基因产物可以被修饰以导致自身死亡。噬菌体可能会递送反义核酸以抑制分枝杆菌基因表达。药物、免疫疗法和疫苗之间的区别可能会变得模糊。
