Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

Chemical Research in Chinese Universities ›› 2012, Vol. 28 ›› Issue (1): 61-66.

• Articles • Previous Articles Next Articles

Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

FENG Lian-shun, LIU Ming-liang*, WANG Shuo, CHAI Yun, LI Su-jie, GUO Hui-yuan

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China

Received:2011-03-23 Revised:2011-06-10 Online:2012-01-25 Published:2011-12-27
Supported by:
Supported by the National Key Project of Major Infectious Disease of China(No.2008ZX10003-006) and the National S&T Major Special Project on Major New Drug Innovation, China(No.2009ZX09301-003).

Abstract

Abstract: A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. smegmatis CMCC 93202. Compounds 3a―3f, 5a, 5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis(MTB) H37Rv ATCC 27294 and MDR-MTB 09710. All the target compounds[ minimum inhibitory concentration(MIC): 0.39―>16 μg/mL] were far more active than rifampin(MIC: 2.0―>256 μg/mL), but less active than moxifloxacin(MIC: 0.1―1.0 μg/mL) against the three tested strains. The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M. smegmatis CMCC 93202, 2 fold more potent than rifampin against MTB H37Rv ATCC 27294, and 16―>64 fold more potent than ethambutol, isoniazid and rifampin against MDR-MTB 09710.

Key words: Moxifloxacin derivative, Antimycobacterial activity, Isatin

FENG Lian-shun, LIU Ming-liang, WANG Shuo, CHAI Yun, LI Su-jie, GUO Hui-yuan. Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives[J]. Chemical Research in Chinese Universities, 2012, 28(1): 61-66.

References

[1] Sriram D., Senthilkumar P., Dinakaran M., Yogeeswari P., China A.,Nagaraja V., J. Med. Chem., 2007, 50, 6232 [2] World Health Organization, Global Tuberculosis Control: A Short Update to the 2009 Report. WHO Report, Geneva, 2009 [3] World Health Organization, Prevention and Control of Multidrug-resistant Tuberculosis and Extensively Drug-resistant Tuberculosis,WHO Report, Geneva, 2009 [4] Sriram D., Aubry A., Yogeeswaria P., Fisher L. M., Bioorg. Med.Chem. Lett., 2006, 16, 2982 [5] Charifson P. S., Grillot A. L., Grossman T. H., Parsons J. D., BadiaM., Bellon S., Deininger D. D., Drumm J. E., Gross C. H., LeTiranA., Liao Y. S., Mani N., Nicolau D. P., Perola E., Ronkin S., ShannonD., Swenson L. L., Tang Q., Tessier P. R., Tian S. K., Trudeau M.,Wang T. S., Wei Y. Y., Zhang H., Stamos D., J. Med. Chem., 2008, 51,5243 [6] Aubry A., Pan X. S., Fisher L. M., Jarlier V., Emmanuelle C., Antimicrob.Agents Chemother., 2004, 48, 1281 [7] Crofton J., Choculet P., Maher D., Guidelines for the Management of Drug-Resistant Tuberculosis WHO/TB/96-210(Rev.1), World Health Organization, Geneva, 1997 [8] Ginsburg A. S., Grosset J. H., Bishai W. R., Lancet Infect. Dis., 2003,3, 432 [9] Sriram D., Yogeeswari P., Basha J. S., Radha D. R., Nagaraja V. J.,Bioorg. Med. Chem., 2005, 13, 5774 [10] Feng L. S., Liu M. L., Wang B., Chai Y., Hao X. Q., Meng S., Guo H.Y., Eur. J. Med. Chem., 2010, 45, 3407 [11] Feng L. S., Liu M. L., Zhang S., Chai Y., Wang B., Zhang Y. B., LvK., Guan Y., Guo H. Y., Xiao C. L., Eur. J. Med. Chem., 2011, 46,341 [12] Liu B. Y., Zhao D. S., Xu D. Q., Xu Z. Y., Chem. Res. Chinese Universities, 2007, 23(2), 163 [13] Zhao C. S., Zhao Y. F., Chai H. F., Gong P., Chem. Res. Chinese Universities, 2006, 22(5), 577 [14] Piscopo E., Diurno M. V., Gogliadi R., Cucciniello M., Veneruso G.,Boll. Soc. Ital. Biol. Sper., 1987, 63, 827 [15] Feng L. S., Liu M. L., Zhang Y. B., Guo H. Y., Chem. Res. Chinese Universities, 2011, 27(6), 981

Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 3

Recommended Articles

Metrics

Comments

[1]	CHEN Jiayi, SHU Wei, WANG Enju. A Fluorescent and Colorimetric Probe Based on Isatin-appended Rhodamine for the Detection of Hg²⁺ [J]. Chemical Research in Chinese Universities, 2016, 32(5): 742-745.
[2]	AYCHILUHIM Tewodros Birhanu, VEDULA Rajeswar Rao. One Pot, Multi-component Synthesis of 3-[(4-Aryl-thiazol-2-yl)-hydrazono]-1,3-dihydro-indole-2-one [J]. Chemical Research in Chinese Universities, 2014, 30(4): 601-604.
[3]	SHANG Jian-li, LI Hui-dong, SHANG Jun, SONG Hai-bin, LI Zheng-ming, .... Syntheses, Crystal Structures and Bioactivities of Two Novel Isatin Derivatives [J]. Chemical Research in Chinese Universities, 2011, 27(4): 595-598.