PMID- 28856604
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20191220
IS  - 1867-1462 (Electronic)
IS  - 1867-1462 (Linking)
VI  - 11
IP  - 2
DP  - 2019 Jun
TI  - In Silico Drug Design of Thiolactomycin Derivatives Against Mtb-KasA Enzyme to 
      Inhibit Multidrug Resistance of Mycobacterium tuberculosis.
PG  - 215-225
LID - 10.1007/s12539-017-0257-0 [doi]
AB  - Tuberculosis (TB) is a leading infectious disease which kills a huge number of 
      people every year over a decade, caused by Mycobacterium tuberculosis. The 
      conventional drugs in the market are no longer effective due to the increasing 
      mycobacterial resistance to antibiotics. Hence, the need of finding efficient 
      drugs to solve this multiple drug resistant factor is becoming an immediate 
      issue. The first-line drugs in current practice for the treatment of TB emphasize 
      on mycolic acid, which protects the bacteria from an immune response generated by 
      the host. A key enzyme involved in this mycolic acid biosynthesis, M. 
      tuberculosis beta-ketoacyl-ACP synthase A (MTB-KasA) is a prime candidate in this 
      study. Thiolactomycin is a natural product inhibitor has shown good inhibitory 
      activity against MTB-KasA. Hence, several thiolactomycin derivatives collected 
      from the literature were taken for absorption, distribution, metabolism, 
      excretion and toxicity prediction, molecular docking and molecular dynamics 
      simulation studies with MTB-KasA. The in silico drug designing methods used in 
      this study suggests that the thiolactomycin derivatives are having a better 
      binding activity against MTB-KasA and among them the ligand C14 is identified as 
      a promising lead molecule to inhibit multidrug resistance of tuberculosis by 
      showing a long time binding activity.
FAU - Durairaj, D Ruban
AU  - Durairaj DR
AUID- ORCID: 0000-0002-2064-8360
AD  - Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, 
      India. ruban.bioinfo@gmail.com.
FAU - Shanmughavel, P
AU  - Shanmughavel P
AD  - Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, 
      India.
LA  - eng
PT  - Journal Article
DEP - 20170830
PL  - Germany
TA  - Interdiscip Sci
JT  - Interdisciplinary sciences, computational life sciences
JID - 101515919
RN  - 0 (Ligands)
RN  - 0 (Thiophenes)
RN  - 82079-32-1 (thiolactomycin)
RN  - EC 2.3.1.41 (3-Oxoacyl-(Acyl-Carrier-Protein) Synthase)
SB  - IM
MH  - 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/*antagonists & inhibitors/metabolism
MH  - *Computer Simulation
MH  - *Drug Design
MH  - Drug Resistance, Multiple, Bacterial/*drug effects
MH  - Hydrogen Bonding
MH  - Ligands
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Mycobacterium tuberculosis/drug effects/*enzymology
MH  - Principal Component Analysis
MH  - Reproducibility of Results
MH  - Thiophenes/chemistry/pharmacology
OTO - NOTNLM
OT  - In silico drug design
OT  - KasA
OT  - Molecular dynamics simulation
OT  - Multidrug resistance
OT  - Thiolactomycin
OT  - Tuberculosis
EDAT- 2017/09/01 06:00
MHDA- 2019/12/21 06:00
CRDT- 2017/09/01 06:00
PHST- 2016/11/06 00:00 [received]
PHST- 2017/08/10 00:00 [accepted]
PHST- 2017/04/24 00:00 [revised]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
AID - 10.1007/s12539-017-0257-0 [pii]
AID - 10.1007/s12539-017-0257-0 [doi]
PST - ppublish
SO  - Interdiscip Sci. 2019 Jun;11(2):215-225. doi: 10.1007/s12539-017-0257-0. Epub 
      2017 Aug 30.