Mycobacterium tuberculosis, growth inhibition

Both ll-oxo-12-hydroxyaerothionin (73) and 11-hydroxyaerothionin (71) induced 60 and 70% inhibition, respectively, of Mycobacterium tuberculosis growth at 12.5 pg/mL, while 11-oxoaerothionin (72) induced no inhibition at all (253). Single spirocyclohexa-dienylisoxazoline bromotyrosine derivatives, aplysinamisine I (120), aplysinamisine n (124), aplysinamisine III (102), purealidin B (109), araplysillin-I (99), and araplysillin-II (100), showed moderate antimicrobial activity (81,83,84). Some of the oxime type bromotyrosine derivatives showed potent antimicrobial activity. Anomoian A (195), a reduced oxime, exhibited strong antimicrobial activity against Staphylococcus aureus at 10 pg/disk. Bacillus. subtilis at 5 pg/disk, and Candida albicans at 25 pg/disk. 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

Fig. 9 Compounds displaying the highest growth inhibition rates against Mycobacterium tuberculosis H37Rv (12.5 pg/ml)...

One patent describes the inhibition of growth of six strains of Mycobacterium tuberculosis by l,3-dicycIohexyl-l,3-diazetidine (78MIP51500) and the corresponding diphenyl derivative shows similar activity (80MIP51500). 

Whole cell growth inhibition screens combined with subsequent target identification using molecular methods have proven viable approaches to the discovery of novel antibacterial inhibitors. Andries and colleagues (2005) at Johnson Johnson employed whole cell assays to discover a series of antimycobacterial diarylquinolines (DARQs). Chemical optimization of a lead compound led to DARQ derivatives exhibiting potent in vitro activities against several mycobacteria including Mycobacterium tuberculosis (Andries et al., 2005 Ji et al., 2006), with MICs below 0.5 pg/mL. Antimycobacterial efficacy in vivo was confirmed for three of the derivatives. 

Molnar, Beladii, and Foldes [69] studied antimycobacterial activity of five phenothiazine derivatives including chlorpromazine, levomeprazine, promazine, promethazine, and diethazine. The growth of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium butyricum was found to be inhibited by chlorpromazine at practically identical concentrations. The minimum inhibitory concentrations for Mycobacterium tuberculosis were chlorpromazine and levomeprazine 10 xg/ml diethazine and promethazine 20 xg/ml whilst chlorpromazine sulphoxide was ineffective even at 100 xg/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on Mycobacterium tuberculosis at 50 xg/ml total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 xg/ml. Preliminary studies in mouse experiments revealed that phenothiazine derivatives were ineffective. 

Aminosalicylate sodium (3.3 to 4 g p.o. q. 8 hours) is indicated as an adjunctive treatment of tuberculosis. It inhibits the formation of folic acid and hence suppresses the growth and reproduction of Mycobacterium tuberculosis. 

Heteronemin (178), first isolated from the sponge Heteromma erecta [175], was toxic to A. salina and gametes of the giant kelp Macrocystis pyrifera at 10 pg/ml and also immobilised the larvae of the red abalone Haliotis rufescens at 1 pg/ml [22]. Furthermore, heteronemin showed antituberculosis activity, inhibiting the growth of Mycobacterium tuberculosis with an MIC of 6.25 pg/ml [176]. Salmahyrtisol B (179), isolated from the Red Sea Hyrtios erecta [177], is related to scalarafiiran... 

Dubos" concluded that lactic acid has a bacteriostatic effect on Mycobacterium tuberculosis, which increased as pH decreased. Experiments carried out with Bacillus coagulans in tomato paste showed that lactic acid was four times more effective regarding the inhibition of bacterial growth compared to malic, citric, propionic, and acetic acid. ... 

Comparison of In Vitro Growth Inhibition of Human Type of Mycobacterium tuberculosis with the In Vivo Protection of Tuberculosis-Infected Guinea Pigs by Essential Oils and Components Thereof... 

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