01370nas a2200145   4500008004100000245011400041210006900155260009000224520069800314100001801012700001901030700002601049700001901075856013001094       2015                        eng d00aHigh throughput screening of inhibitors for tuberculosis at NCL : a novel drug discovery initiative from CSIR0 aHigh throughput screening of inhibitors for tuberculosis at NCL   aCSIR-National Chemical Laboratory, PunebCSIR-National Chemical Laboratory, PunecSEP3 a<p>Discover and develop novel drugs that are effective at curing latent, drug sensitive and drug resistant TB Study the biology of tuberculosis bacilli in great detail to identify new metabolic pathways that may be vulnerable to drugs Test thousands of potential drugs in our screening facility to find new compounds or new compound classes that kill TB bacteria Increase throughput up to 20,000 compounds at a time Develop novel screens using conditions that mimic those the TB bacteria encounters in the human body Utilize medical chemistry to optimize the structures of compounds so that they kill TB bacteria in a more potent fashion and are non-toxic Meet the challenges from industry</p>1 aManek, Hardik1 aNawale, Laxman1 aJadhav, Nandadeep, J.1 aSarkar, Dhiman  uhttps://library.ncl.res.in/content/high-throughput-screening-inhibitors-tuberculosis-ncl-novel-drug-discovery-initiative-csir02112nas a2200241   4500008004100000245013000041210006900171260000800240300001200248490000800260520125600268100002401524700002601548700002601574700002301600700002401623700001801647700001901665700001801684700002001702700001901722856012901741       2016                        eng d00aDesign, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents0 aDesign synthesis and biological evaluation of novel azaspiro ana  cOCT  a475-4870 v1223 a<p>The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. Linezolid comprises of a morpholine ring which is known for its metabolism related liabilities. Therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. Furthermore, the replacement of N-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried out. The title compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Subsequent structure-activity relationship (SAR) studies identified several compounds with mixed antibacterial and antitubercular profiles. Compound 22 (IC50 0.72, 0.51, 0.88, 0.49 mu g/mL for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, respectively) exhibited similar antibacterial profile as I. The N-acetyl derivative 18 was similar to 1 in antitubercular profile. Thus, the present study successfully demonstrated the use of azaspiro substructure in the medicinal chemistry of antibacterial and antitubercular agents. (C) 2016 Elsevier Masson SAS. All rights reserved.</p>1 aGadekar, Pradip, K.1 aRoychowdhury, Abhijit1 aKharkar, Prashant, S.1 aKhedkar, Vijay, M.1 aArkile, Manisha, A.1 aManek, Hardik1 aSarkar, Dhiman1 aSharma, Rajiv1 aVijayakumar, V.1 aSarveswari, S.  uhttps://library.ncl.res.in/content/design-synthesis-and-biological-evaluation-novel-azaspiro-analogs-linezolid-antibacterial