I am looking forward to design a drug against Mycobacterium tuberculosis, so what are aspects (please point out some examples) should I look for ? We can target some enzymes which are not involved in human cells, but what type of cystosolic enzyme should be a good candidate please specify.
There are many papers on the subject of mycobacterial drug targets. Here are a few of them.
https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(10)00150-4.pdf
Article Novel drug targets for Mycobacterium tuberculosis: 2-heteros...
Article The Expanding Diversity of Mycobacterium tuberculosis Drug Targets
Mycobacterium tuberculosis is the causative agent of TB, TB is difficult to treat effectively because of the unusual structure and chemical structure of the mycobacterium cell wall, which hampers the entry of drugs and makes many antibiotics ineffective.
you can design drug that prevents bacteria from producing RNA by relying on the genetic content of DNA by inhibiting the enzyme responsible for that contained within the DNA-dependent RNA polymerase
Since the cell wall of TB bacteria is waxy and unique (containing the waxy acids beta type in addition to mycolic acid, so can design an antibiotic works on these acids and prevents the formation of wax, especially mycolic acid
There are many papers on the subject of mycobacterial drug targets. Here are a few of them.
https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(10)00150-4.pdf
Article Novel drug targets for Mycobacterium tuberculosis: 2-heteros...
Article The Expanding Diversity of Mycobacterium tuberculosis Drug Targets
Some other links
https://academic.oup.com/nar/article/46/D1/D413/4584621
journals.plos.org/plosone/article?id=10.1371/journal.pone.0032833
The M. tuberculosis subject is a tricky and complicated one. As a mycobacteriologist I can not suggest you an easy way for disgning a drug against the bacterium, as you need to consider several picks and tricks. I advise you to read the huge litrature contains many papers and find out the ambiguities and start your research more sophisticated.
Dear Prem Prakash i send you an inetresting articleabout the issue
Drug Des Devel Ther. 2016 Jul 18;10:2299-310. doi: 10.2147/DDDT.S104037. eCollection 2016.
Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents.
Kar SS1, Bhat G V1, Rao PP2, Shenoy VP3, Bairy I4, Shenoy GG1.
other interesting study
Pharm Biol. 2015;53(10):1474-80. doi: 10.3109/13880209.2014.986687. Epub 2015 Apr 10.
Antimicrobial activity of pomegranate fruit constituents against drug-resistant Mycobacterium tuberculosis and β-lactamase producing Klebsiella pneumoniae.
Dey D1, Ray R, Hazra B.
Targeting Mycobacterium is a complex area and several reports are available. Issues involved relate to penetration of the chemotherapeutic agent into the alveolar macrophages (AMs) to achieve high concentrations, and the environment surrounding the macrophages, entry mechanisms into the macrophages are used as approaches.
Some useful references-
1) D.E. Minnikin, S.M. Minnikin, J.H. Parlett, M. Goodfellow, M.
Magnusson, Mycolic acid patterns of some species of Mycobacterium,
Arch. Microbiol 139 (2) (1984) 225-231.
2) J.D. Ernst, Macrophage receptors for Mycobacterium tuberculosis, Infect.Immunity. 66 (4) (1998) 1277-1281.
3] S.H. El-Etr, J.D. Cirillo, Entry mechanisms of mycobacteria, Front. Biosci.
6 (2001) D737-D747.
4) S. Majumdar, S.K. Basu, Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery, Antimicrob. Agents Chemother. 35 (1) (1991) 135-140.
Mala Menon Adam B Shapiro Azar Dokht Khoravi Thank you all for your valuable suggestions. I would go through those papers and work accordingly.
Kind Regards
Prem
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