Mycobacterium tuberculosis, growth

Novel inhibitors of Mycobacterium tuberculosis growth based on modified pyrimidine nucleosides and their analogues 13UK896. 

Gilmore SA, Schelle MW, Holsclaw CM, Leigh CD, Jain M, Cox JS, Leary JA, Bertozzi CR (2012) Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human macrophages. ACS Chem Biol 7 863-870... 

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)...

Flavonoid sulphates such as quercetin 3,7-di-O-methyl 3-sulphate and kaempferol 7-0-methyl 3-sulphate, which inhihited the growth of Mycobacterium tuberculosis and Klebsiella pneumoniae, were isolated from the -hutanol fraction of 80% methanol extract of Argyreia speciosa (Burm. f) Boj. (Convolvulaceae), while flavonoids with mti-Helicobacter pylori activity, such as quercetin 3-methyl ether (isorhamnetin) (Fig. 3), were isolated from Cistus laurifolius L. (Cistaceae). ... 

Snow GA (1965) Isolation and Structure of Mycobactin T, a Growth Factor from Mycobacterium tuberculosis. Biochem J 97 166... 

Tuberculosis can be an extremely difficult disease to manage. Most cases are infected with Mycobacterium tuberculosis. These organisms are different from other microorganisms in several aspects. They have another sensitivity spectrum and their growth rate is very slow. The mycobacterium can remain dormant for extended periods of time. Furthermore tuberculosis is an intracellular infection and the mycobacterium is therefore difficult to reach by antimy-cobacterials. All these factors contribute to the fact... 

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). 

An iron-containing growth factor from Mycobacterium tuberculosis. Biochem. J. 81, 4P (1961). 

G Harth, MA Horwitz (1999) An inhibitor of exported Mycobacterium tuberculosis glutamine synthetase selectively blocks the growth of pathogenic mycobacteria in axenic culture and in human monocytes extracellular proteins as potential novel drug targets, J Exp Med 189(9) 1425-1436... 

Based on the patient s history and lab information, he was started on a regimen of isoniazid, rifampin, pyrazinamide, and ethambutol while waiting for definitive cultures. (Six weeks later, definitive culture results demonstrated growth of Mycobacterium tuberculosis.) The patient returned to the clinic complaining of blurred vision and an inability to differentiate between green and red colors. 

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. 

PCR can provide valuable diagnostic information in medicine. Bacteria and viruses can be readily detected with the use of specific primers. For example, PCR can reveal the presence of human immunodeficiency virus in people who have not mounted an immune response to this pathogen and would therefore be missed with an antibody assay. Finding Mycobacterium tuberculosis bacilli in tissue specimens is slow and laborious. With PCR, as few as 10 tubercle bacilli per million human cells can be readily detected. PCR is a promising method for the early detection of certain cancers. This technique can identify mutations of certain growth-control genes, such as the ras genes (Section 15.4 2). The... 

Ethambutol is tuberculostatic and acts against Mycobacterium tuberculosis and Mycobacterium kansasii as well as some strains of Mycobacterium avium complex. It has no effect on other bacteria. The sensitivities of non-tuberculous mycobacteria are variable. Ethambutol suppresses the growth of most isoniazid-resistant and streptomycin-resistant tubercle bacilli (1). 

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