C-labelled substrate ; (b) antigenic assays by the enzyme-linked immunosorbent assays (ELISA) ;

14 C-labelled substrate ; (b) antigenic assays by the enzyme-linked immunosorbent assays (ELISA) ;

(c) DNA probes ; nucleic-acid amplification techniques ; and (d) the restriction fragment length

polymorphism (RFLP) analysis of the resulting genomic DNA.*

Metabolism of Mycobacteria : It has been established that the ‘biochemical constitution’ of mycobacteria is of rather complex nature. The meticulous meaningful researches have discovered certain

novel chemical structures, but the ensuing relationship between these and the pathogenic and

biologic activities of mycobacteria yet remain to be elucidated and expatiated satisfactorily. Though copious volume of informations with respect to the precise metabolism of mycobacteria are available ; however, the exhaustive overall picture of the mycobacterial metabolism is far from plausible acceptable completion.

Mycosides : Smith et al., (1960)** reported mycosides which are the glycolipids and peptidoglycolipids type specific of mycobacteria. McLennan et al. (1961)*** ascertained that they have in common the particular terminal saccharide groups essentially containing rhamnoses

*Watt B : Rev. Med. Microbiol, 4 : 97, 1993. **Smith DW : Nature, 186 : 887, 1960. ***Mclennan AP et al. : Biochem. J., 80 : 309, 1961.

783 O -methylated in different strategical positions. Lederer (1967) assified the mycosides into two major

ANTIMYCOBACTERIAL DRUGS

classes, namely : (a) Phenolic glycolipids — having brached-chain fatty acids, and (b) Peptidoglucolipids — consisting of one mole each of : sugar moiety, fatty acid, and short peptide. In general, the glycolipids and the peptidoglycolipids are held absolutely resposible for the apparent

ropelike structures which is quite obvious in one of the outer layers of the mycobacteria on being examined by using the unique technique of negative staining.*

Mycobactin P : Mycobactin P is a natural product, first and foremost isolated in 1946, which possesses an exceptional iron-chelating characteristic feature.

Mycobactin S : Mycobactin S happens to be the most active of these factors exhibiting distinct growth stimulation at a concentration as low as 0.3 ng . mL –1 .

Mycobactin M : Mycobactin M designates the structure of M-type factors.

MYCOBACTIN P : R 1 =C 17 H 34 ;R 2 = CH 3 ;R 3 =H;R 4 =C 2 H 5 ;R 5 = CH 3 ;

MYCOBACTIN S : R 1 =C 17 H 34 ;R 2 =H;R 3 =H;R 4 = CH 3 ;R 5 =H;

MYCOBACTIN M : R 1 = CH 3 ;R 2 =H;R 3 = CH 3 ;R 4 =C 17 H 34 ;R 5 = CH 3 ; The latest knowledge with respect to the chemistry and functions of mycobactins may be exploited

skilfully in a wide spectrum of approaches to the intensive and extensive search for antimycobacterial drugs.** In actual practice, one such approach may essentially involve critical and exhaustive screening of compounds that interfere at certain specific point in the pathway of biosynthesis of mycobactins ;

C HAPTER

and selecting only such compounds which inhibited exclusively the bacterial growth under iron-limiting

conditions. Thus, one may justifiably link up the primary role of action of para-aminosalicylic acid (PAS) with the ensuing inhibition of the mycobactin synthesis.

It has been amply proved and established that both tuberculosis and the Mycobacterium avium complex infection are enhanced significantly by virtue of the fact that the relatively high number of AIDS patients that usually coexist specifically in the huge inner city populations, and also due to plenty of homeless shelters. In actual practice, the antimicrobial drugs that are solely employed for the effective

*Barksdale L and Kim KS : Bacteriol Rev., 41, 217, 1977. **Braun V et al. (eds) : The Future of Antibiotherapy and Antibiotic Research, Academic Press, London (UK), 1981.

MEDICINAL CHEMISTRY

treatment of Mycobacterium avium complex essentially include : rifabutin, the new macrolides (viz.,

clarithromycin and azithromycin), the fluoroquinolones, and combination regimens of ethambutol

(or other tuberculosis drugs) with either clarithromycin or azithromycin.