02112nas 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