4298
M. Kidwai et al. / Bioorg. Med. Chem. Lett. 15 (2005) 4295–4298
Table 3. Antibacterial activity of different compounds (2a–d and 3a–d) and ampicillin by Broth Microdilution MIC method
Concentration used (lg/ml)
Antibacterial activity against standard strains—Compounds
2a
2b
2c
2d
3a
3b
3c
3d
Ampicillin
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
0.5
1.0
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
–
+
+
+
–
+
+
+
+
–
+
+
+
+
–
2.0
4.0
8.0
–
16.0
32.0
64.0
128.0
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1, E. coli (ATCC 25922); 2, P. aeruginosa (ATCC 27853); 3, S. aureus (ATCC 25923); +, resistant; À, susceptible.
6. Hafez, E. A.; Elnagdi, M. H.; Elagemey, A. G. A.;
El-Taweel, F. M. A. A. Heterocycles 1987, 26, 903.
7. Khafagy, M. M.; El-Wahas, A. H. F. A.; Eid, F. A.;
El-Agrody, A. M. Farmaco 2002, 57, 715.
8. Smith, W. P.; Sollis, L. S.; Howes, D. P.; Cherry, C. P.;
Starkey, D. I.; Cobley, N. K. J. Med. Chem. 1998, 41,
787.
9. Hiramoto, K.; Nasuhara, A.; Michiloshi, K.; Kato, T.;
Kikugawa, K. Mutat. Res. 1997, 395, 47.
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1997, 7, 3165.
11. Dell, C.P.; Smith, C.W. European Patent Appl. EP
537949, Chem. Abstr. 1993, 119, 139102d.
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Cancer Res. 1975, 35, 3750.
plates, 0.1 ml of Mueller Hinton Broth was added to
each of the 96 wells. Doubling dilutions of each com-
pound were made in the wells, thus a plate contained
0.5–128 lg/ml dilutions of eight different compounds
and of ampicillin. In each plate, one well was kept as po-
sitive control (broth + inoculum) and another one as neg-
ative control (broth only). The inoculum was adjusted to
a turbidity equivalent to McFarland 0.5 turbidity stan-
dard. The inoculum was suitably diluted so as to get a
final concentration of approximately 5 · 105 cfu/ml of
bacteria in each well. Each well was inoculated with
0.01 ml of the prepared inoculum using a multichannel
micropipette and the plates were incubated overnight at
37 ꢁC. The MICs of these compounds and ampicillin were
determined by using the standard protocol of NCCLS
Broth Microdilution MIC method.18
14. Eiden, F.; Denk, F. Arch. Pharm. Weinhein Ger (Arch.
Pharm.) 1991, 324, 353.
15. Kidwai, M.; Saxena, S.; Khan, M.K.R.; Thukral, S.S.
European J. Med. Chem. 2005 (in press).
16. Kidwai, M.; Mothsra, P.; Mohan, R.; Biswas, S. Bioorg.
Med. Chem. Lett. 2005, 15, 915.
Acknowledgment
17. Kidwai, M.; Venkataramanan, R.; Dave, B. Green Chem.
2001, 3, 278.
18. NCCLS, Performance Standards for Antimicrobial Sus-
ceptibility Testing: Twelfth Information Supplement M,
In National Committee for Clinical Laboratory Stan-
dards, Wayne, PA, 2002, pp 100–512.
The authors M. Kidwai and S. Saxena are thankful to
University Grants Commission, New Delhi, for financial
assistance.
References and notes
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