One of the important reasons for the rise in the tuberculosis epidemic is the widespread prevalence of drug-resistant Mycobacterium tuberculosis, especially the emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB), which has led to an outbreak of multidrug-resistant tuberculosis (MDR-TB). In recent years, the emergence of extensively drug-resistant TB (XDR-TB), i.e., the emergence of resistance to any fluoroquinolones and at least one of the three second-line injectable drugs (capreomycin sulfate, kanamycin, and amikacin) on top of multidrug-resistant TB, has made TB control more difficult and made the global TB epidemic more severe. The occurrence and prevalence of drug-resistant tuberculosis will render current tuberculosis treatments ineffective, thus making tuberculosis incurable again, so the development of new and effective anti-tuberculosis drugs has become one of the key measures to combat tuberculosis. Rifamycins Since the first clinical application of rifampicin in 1962, rifamycins have occupied an important position in the treatment of tuberculosis, and their research work has been very active. The newly developed rifabutin in recent years is a derivative of spiro-piperidine rifamycin S, which is mainly used in the treatment of drug-resistant Mycobacterium tuberculosis and nontuberculous mycobacterial disease. In recent years, a large number of new derivatives of benzofosfomycin have been synthesized abroad, among which a series of 3′-hydroxy-5amino benzofosfomycin rifamycin developed by Jongbun Japan is the most prominent, and it was found through research that the antibacterial activity of these compounds against Mycobacterium tuberculosis is significantly better than that of rifampicin, and the most promising compounds at present are 3′-hydroxy-5′-(4-isobutyl-1-piperazinyl)benzofosfomycin Another new semi-synthetic rifamycin is rifametane (SPA-S-565), whose antibacterial spectrum and activity are reported to be comparable to rifampicin and is now in phase II clinical trials. There are also many other piperidine long-acting rifamycins in the research stage, such as CGP27557, CGP29861, CGP7040, etc. Among them, CGP7040 is the most promising, and in vitro tests have shown that its antibacterial activity against rifampicin-susceptible Mycobacterium tuberculosis is 4-8 times higher than that of rifampicin. Fluoroquinolones These drugs are active against Mycobacterium tuberculosis both inside and outside macrophages, and also against nontuberculous mycobacteria. Its main advantages are easy absorption through the gastrointestinal tract, long elimination half-life, high tissue penetration, large distribution volume, relatively small adverse effects, and suitable for long-range administration. The more researched drugs in recent years include ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gepafloxacin. Among them, levofloxacin (levofloxacin) has a very high concentration of absorption in the body and penetration into the bronchial-lung barrier, and the incidence of adverse reactions is only 2.77%, so it has good antibacterial activity, excellent pharmacokinetics and high safety and synergistic effects with other anti-tuberculosis drugs, and is the drug of choice for the treatment of multidrug-resistant tuberculosis. As a fourth-generation fluoroquinolone, moxifloxacin has better antibacterial activity than levofloxacin against Mycobacterium tuberculosis in the rapid multiplication phase, while its antibacterial effect is slightly lower than levofloxacin in the stationary phase. It is commonly used in the treatment of relapsed and multidrug-resistant tuberculosis. The fourth-generation fluoroquinolone cetafloxacin developed by Daiichi Pharmaceutical Co., Ltd. has been reported to have good antituberculosis activity against Mycobacterium tuberculosis in animal studies, and further studies are needed. These drugs are semi-synthetic derivatives with lactone ring size or substitution type different from erythromycin, and their anti-tuberculosis activity is higher than that of erythromycin. Among them, roxithromycin has the strongest activity against Mycobacterium tuberculosis, followed by clarithromycin. Aminoglycosides Among these drugs, amikacin, isopamycin, capreomycin, and balomycin are widely used. Among them, amikacin is a semi-synthetic product of kanamycin with the introduction of amino hydroxybutyryl chain, and its activity against Mycobacterium tuberculosis is higher than that of kanamycin, while its toxic side effects are significantly lower than that of kanamycin, so it has been replaced clinically and is mainly used for the treatment of drug-resistant Mycobacterium tuberculosis infection. Isopamycin is a combination of gentamicin B and kanamycin A and is effective against amikacin-resistant Mycobacterium tuberculosis. Cofilomycin is unidirectionally resistant to amikacin and should be used for treatment when amikacin resistance is present. Barongomycin, an aminoglycoside obtained from streptomycin cultures, is cross-resistant to streptomycin and kanamycin and is mainly used in the treatment of multidrug-resistant tuberculosis. Pyrazinamides Pyrazinamides are traditional first-line antituberculosis drugs, and recently new insights have been gained into their bactericidal effects. According to Mitchison’s new thesis, although most of the bacteria in the lesion are present extracellularly at the beginning of TB treatment, pyrazinamide is more bactericidal than isoniazid when some of these bacteria cause an inflammatory response that decreases the pH and inhibits the growth of some bacteria. Therefore, the addition of pyrazinamide at the beginning 2-3 months of a short course of chemotherapy is necessary to achieve a high, almost recurrence-free cure rate. New pyrazinamide derivatives such as n-octyl pyrazinate, tert-butyloxy methyl ester, thionamide and thiosemicarbazide are being studied abroad, but no promising drug has been found yet for development. Aminothiourea derivatives Aminothiourea, also known as aminothiourea, has been rarely used in clinical applications due to its poor efficacy and many adverse effects. Recently, several new aminothiourea derivatives have been synthesized, among which 2-acetylquinoline-N4-pyrrolidine aminothiourea has better antibacterial activity than aminothiourea. In addition, vinyl methyl ketone aminothiourea shows better efficacy in the treatment of experimental tuberculosis in mice. Phenothiazines This is a class of drugs used for leprosy, but in recent years it has also been tried in the treatment of drug-resistant tuberculosis, with clofazimine being the most studied. This drug inhibits the growth of Mycobacterium tuberculosis by binding to its DNA and inhibiting transcription. In addition, it can restore phagocytosis in combination with β-interferon, but clofazimine can cause life-threatening abdominal pain and organ damage, so its clinical use is limited. Pyrroles Pyrroles are antifungal agents, and they have recently been found to have anti-tuberculosis mycobacterial activity as well. Dibenzimidazole has strong antituberculosis activity against Mycobacterium tuberculosis. BM212 has a novel structure and is one of the more potent antituberculosis drugs in the pyrrole class, and does not cross-resist with first-line antituberculosis drugs. Phenothiazines Phenothiazines were originally used as antipsychotic drugs, but it was found that chlorpromazine, thioetherazine and trifluoperazine also have anti-tuberculosis activity. Their anti-tuberculosis effect is mainly related to the presence of calmodulin-like proteins in Mycobacterium tuberculosis, because phenothiazines are calmodulin antagonists. Chlorpromazine at concentrations ranging from 0.23 to 3.6 µg/mL can inhibit Mycobacterium tuberculosis in macrophages and enhance the effect of drugs such as streptomycin, isoniazid and pyrazinamide on intracellular Mycobacterium tuberculosis. Trifluoperazine, a piperazine derivative of phenazine, has some antibacterial activity against Mycobacterium tuberculosis. Although the above describes the research progress of several major classes of drugs in anti-tuberculosis treatment, but in fact, there is still a considerable distance from the needs in clinical practice work of tuberculosis, especially the treatment of drug-resistant tuberculosis. With the continuous attention to tuberculosis and the efforts of researchers, many new compounds with high anti-tuberculosis activity have been discovered, while the discovery of new targets of anti-tuberculosis drugs, new mechanisms of action anti-tuberculosis The discovery of new targets for anti-tuberculosis drugs, the screening of new mechanisms of action for anti-tuberculosis drugs, and targeted drug delivery systems for tuberculosis treatment have brought new hope for the treatment of tuberculosis. In order to control tuberculosis, especially drug-resistant tuberculosis, the development of new and efficient anti-tuberculosis drugs has become an urgent global task.