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Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae which has been plaguing mankind for ages. The first effective medicine to treat that illness was dapsone (1946) and it has been used until now [1]. Since then, there has been developed only one more new drug, clofazimine (1), which is, together with dapsone, listed as medicine used to cure leprosy (J 04 BA). The other drugs which are currently employed in leprosy therapy used to be utilised in treatment of other bacterial diseases. Clofazimine (1) was first synthesised in 1954 and has marked antibacterial and anti-inflammatory effects [2-8]. The method of preparation of clofazimine (1) consists of two stages (Scheme 1) [9, 10]. Minocycline (3) is a semisynthetic antibiotic of the tetracycline group with the mycobactericidal activity, obtained by chemical modification of tetracycline derivatives [11-13]. The substrates to synthesise minocycline are the metabolism products of S. aureofaciens or S. psammoticus - 6-demethyltetracycline (4a) or 7-chloro-6-demethyltetracycline (4b) [14-16]. 6-Demethyl-6-deoxyteracycline (5) is obtained as a result of reduction of compounds 4a and 4b, which may be transformed in several ways into minocycline (3) (Scheme 2, 3, 4) [17-30]. Amongst the macrolide antibiotics also the semisynthetic derivatives of erythromycin A, such as clarithromycin (15), azitromycin (16) and telithromycin (17) show some anti-leprosy features [12, 26, 32, 33]. Telithromycin (17) was introduced to medicine in 1995 and belongs to the group of ketolides, the latest generation of macrolides [12, 39, 40-45]. Following the in vitro and in vivo research it has been stated that the fluoroquinolones demonstrate mycobactericidal activity (Table 1) [47-51]. The World Health Organisation (WHO) recommends the use of fluoroquinolones in the multidrug therapy (MDT) together with other chemotherapeutics [108-113]. Rifampicin (26), a drug from the ansamycin antibiotic group, turned out to be an extremely effective weapon against leprosy [72, 73]. It is produced by chemical modification of a fermentation product of S. mediterranei [31, 74]. Rifampicin derivatives rifapentine (27) and rifabutin (28) are manifesting strong reactivity against Mycobacterium leprae, sometimes even surpassing rifampicin (26) (Table 2) [31, 72]. In the treatment of leprosy it is important to cure not only the causes but also the effects of the disease. That is why a wide range of complementary drugs is introduced. Especially steroids such as prednisolone (30), prednisone (31), dexamethasone (32) and fusidic acid (34) are important. The enumerated above steroids have strong anti-inflammatory effects as well as prevent nerve damage leading to smaller and lesser disability [2, 85]. Dexamethasone (32) is particularly efficient in conjunction with azathioprine (33) [90]. In the case of fusidic acid (34) it has been proved that it reveals weak bacteriostatic activity against the Gram-positive bacteria, including Mycobacterium leprae [7, 26]. Leprosy treatment involves the use of huge doses of bactericidal and bacteriostatic drugs what may lead to a life-threatening shock. In such circumstances, the most valuable medicine seems to be thalidomide (35) [82, 102-105]. WHO has prepared some programmes of leprosy treatment, recommending a diversion from a single drug to multidrug therapy (MDT). Implementation of the MDT therapy brings about numerous advantages such as economic advantages, shortening of treatment time and particular drug resistance prevention [7, 11, 107-109]. Leprosy, despite the tiny number of effective medicines, is totally curable. There have been continuous signals about utilising common and popular antibacterial drugs in leprosy treatment. Yet, it should be taken into consideration, that all action taken against that disease is limited to fighting bacteria but not preventing transmission.