successfully used in the treatment regimen for drug-resistant TB. This combinatorial chemotherapy toward MDR-TB, XDR-TB, and TDR-TB can definitely
improve the life expectancy and reduce the mortality rate of TB patients to some
extent. The main obstacle in the current anti-TB drug discovery program is the drug
toxicity, mode of delivery, and duration of medication. This can surmount if new
oral drugs with good pharmacokinetic profile and anti-TB activity at the nanomolar
level can be discovered for patient compliance and safety.
Acknowledgements The author ACP acknowledges Kerala State Council for Science,
Technology & Environment (KSCSTE) for awarding Junior Research Fellowship (Grant No:1132/
2013/KSCSTE), India. The authors thank Indian Council for Medical Research (ICMR) and
Department of Biotechnology (DBT; BT/PR5659/MED/29/564/2012), Government of India, New
Delhi, India, for financial support. We also acknowledge gratefully Centre for Nanosciences and
Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Kochi, for the
infrastructure support.
References
1. World Health Organization (2017) Global tuberculosis report 2017
2. Ducati RG, Ruffino-Netto A, Basso LA, Santos DS (2006) The resumption of consumption:
a review on tuberculosis. Memórias do Instituto Oswaldo Cruz 101:697–714
3. Strebhardt K, Ullrich A (2008) Paul Ehrlich’s magic bullet concept: 100 years of progress.
Nat Rev Cancer 8:473–480
4. Bloom BR, Murray CJ (1992) Tuberculosis: commentary on a reemergent killer. Science
257:1055–1064
5. Zhang Y (2005) The magic bullets and tuberculosis drug targets. Annu Rev Pharmacol
Toxicol 45:529–564
6. Cole S, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon S, Eiglmeier K,
Gas S, Barry Iii C (1998) Deciphering the biology of Mycobacterium tuberculosis from the
complete genome sequence. Nature 393:537–544
7. Chaitanya M, Babajan B, Anuradha C, Naveen M, Rajasekhar C, Madhusudana P,
Kumar CS (2010) Exploring the molecular basis for selective binding of Mycobacterium
tuberculosis Asp kinase toward its natural substrates and feedback inhibitors: a docking and
molecular dynamics study. J Mol Model 16:1357–1367
8. da Cunha EF, Barbosa EF, Oliveira AA, Ramalho TC (2010) Molecular modeling of
Mycobacterium tuberculosis DNA gyrase and its molecular docking study with gatifloxacin
inhibitors. J Biomol Struct Dyn 27:619–625
9. Khedkar SA, Malde AK, Coutinho EC, Srivastava S (2007) Pharmacophore modeling in
drug discovery and development: an overview. Med Chem 3:187–197
10. Yuan T, Sampson NS (2018) Hit generation in TB drug discovery: from genome to
granuloma. Chem Rev 118:1887–1916
11. Jarlier V, Nikaido H (1994) Mycobacterial cell wall: structure and role in natural resistance
to antibiotics. FEMS Microbiol Lett 123:11–18
12. Brennan PJ, Crick DC (2007) The cell-wall core of Mycobacterium tuberculosis in the
context of drug discovery. Curr Top Med Chem 7:475–488
13. Trefzer C, Škovierová H, Buroni S, Bobovská A, Nenci S, Molteni E, Pojer F, Pasca MR,
Makarov V, Cole ST (2011) Benzothiazinones are suicide inhibitors of mycobacterial
decaprenylphosphoryl-b-D-ribofuranose 2′-oxidase DprE1. J Am Chem Soc 134:912–915
Impact of Target-Based Drug Design in Anti-bacterial …
337
improve the life expectancy and reduce the mortality rate of TB patients to some
extent. The main obstacle in the current anti-TB drug discovery program is the drug
toxicity, mode of delivery, and duration of medication. This can surmount if new
oral drugs with good pharmacokinetic profile and anti-TB activity at the nanomolar
level can be discovered for patient compliance and safety.
Acknowledgements The author ACP acknowledges Kerala State Council for Science,
Technology & Environment (KSCSTE) for awarding Junior Research Fellowship (Grant No:1132/
2013/KSCSTE), India. The authors thank Indian Council for Medical Research (ICMR) and
Department of Biotechnology (DBT; BT/PR5659/MED/29/564/2012), Government of India, New
Delhi, India, for financial support. We also acknowledge gratefully Centre for Nanosciences and
Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Kochi, for the
infrastructure support.
References
1. World Health Organization (2017) Global tuberculosis report 2017
2. Ducati RG, Ruffino-Netto A, Basso LA, Santos DS (2006) The resumption of consumption:
a review on tuberculosis. Memórias do Instituto Oswaldo Cruz 101:697–714
3. Strebhardt K, Ullrich A (2008) Paul Ehrlich’s magic bullet concept: 100 years of progress.
Nat Rev Cancer 8:473–480
4. Bloom BR, Murray CJ (1992) Tuberculosis: commentary on a reemergent killer. Science
257:1055–1064
5. Zhang Y (2005) The magic bullets and tuberculosis drug targets. Annu Rev Pharmacol
Toxicol 45:529–564
6. Cole S, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon S, Eiglmeier K,
Gas S, Barry Iii C (1998) Deciphering the biology of Mycobacterium tuberculosis from the
complete genome sequence. Nature 393:537–544
7. Chaitanya M, Babajan B, Anuradha C, Naveen M, Rajasekhar C, Madhusudana P,
Kumar CS (2010) Exploring the molecular basis for selective binding of Mycobacterium
tuberculosis Asp kinase toward its natural substrates and feedback inhibitors: a docking and
molecular dynamics study. J Mol Model 16:1357–1367
8. da Cunha EF, Barbosa EF, Oliveira AA, Ramalho TC (2010) Molecular modeling of
Mycobacterium tuberculosis DNA gyrase and its molecular docking study with gatifloxacin
inhibitors. J Biomol Struct Dyn 27:619–625
9. Khedkar SA, Malde AK, Coutinho EC, Srivastava S (2007) Pharmacophore modeling in
drug discovery and development: an overview. Med Chem 3:187–197
10. Yuan T, Sampson NS (2018) Hit generation in TB drug discovery: from genome to
granuloma. Chem Rev 118:1887–1916
11. Jarlier V, Nikaido H (1994) Mycobacterial cell wall: structure and role in natural resistance
to antibiotics. FEMS Microbiol Lett 123:11–18
12. Brennan PJ, Crick DC (2007) The cell-wall core of Mycobacterium tuberculosis in the
context of drug discovery. Curr Top Med Chem 7:475–488
13. Trefzer C, Škovierová H, Buroni S, Bobovská A, Nenci S, Molteni E, Pojer F, Pasca MR,
Makarov V, Cole ST (2011) Benzothiazinones are suicide inhibitors of mycobacterial
decaprenylphosphoryl-b-D-ribofuranose 2′-oxidase DprE1. J Am Chem Soc 134:912–915
Impact of Target-Based Drug Design in Anti-bacterial …
337