Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and Antitubercular Activity of 6-Chloro (Unsubstituted)- 2-Methoxy-9-Substituted Acridine Derivatives

  • Aly, Enayat I. (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University) ;
  • Abadi, Ashraf H. (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University)
  • Published : 2004.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Several analogues of the general formulae 2-methoxy-9-substituted acridine and 6-chloro-2-methoxy-9-substituted acridine were synthesized and evaluated in vitro at 6.25 $\mu\textrm{g}$/mL against M. tuberculosis $H_{37}Rv$. Compounds 15 and 17 showed potential antitubercular activity with 100％ inhibition to the virulent mycobacterium.

Keywords

References

  1. Alberghina, M. and Palermo, F., Mutational studies of the drugr-resistance of M. tuberculosis with special reference to ${\rho}$-aminosalicylic acid, ethambutol, isoniazid and rifampicin. Boll. 1st. Sieroter. Milan, 54, 437-444 (1975)
  2. Baca, A. M., Sirawarapom, R., Turley, S., Sirawarapom, W., and Hoi, W. G., Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J. Mol. Biol., 302, 1193-1212 (2000) https://doi.org/10.1006/jmbi.2000.4094
  3. ChemSketch 5.0 freeware, Advanced Chemistry Development Inc. 90 Adelaide Street West, Suite 600 Toronto, Ontario M5H 3V9, Canada.
  4. Collins, L. A. and Franzblau, S. G., Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother., 41, 1004-1009 (1997)
  5. Dye, C., Scheele, S., Dolin, P., Pathania, V., and Raviglione, M. C., Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence and mortality by country. WHO global surveillance and monitoring project. JAMA, 282, 677-686 (1999) https://doi.org/10.1001/jama.282.7.677
  6. Ellner, J. J., Goldberger, M. J., and Parenti, D. M., Myco-bacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. J. Infect. Dis.,163, 1326-1335 (1991) https://doi.org/10.1093/infdis/163.6.1326
  7. EPI Suite v. 3.11, freeware developed by the Environmental Protection Agency EPA and Syracuse Research corporation.
  8. Evans, K. D., Nakasone, A. S., Sutherland, P.A, de la Maza, L. M., and Peterson, E. M., Identification of Mycobacterium tuberculosis and Mycobacterium avium- M. intracellulare directly from primary BACTEC cultures by using acridiniumester- labeled DNA probes. J. Clin. Microbiol., 30, 2427-2431 (1992)
  9. Farmer, P. and kim, J. Y, Community based approaches to the control of multidrug-resistant tuberculosis 'DOTS-plus', BMJ, 317, 671-674 (1998) https://doi.org/10.1136/bmj.317.7159.671
  10. HyperChem 6.0, Hypercube Inc., 1115 N. W. 4th street, Gainesville, FI 32601, USA.
  11. lIseman, M. D., Treatment of multidrug-resistant tuberculosis. N. Engl. J. Med., 329, 784-791 (1993) https://doi.org/10.1056/NEJM199309093291108
  12. Ismail, K. A. and Koreish, E. A., Synthesis of 9-{4-[2-(substituted amino)ethoxy]phenoxy}2-methoxyacridines as potential antimicrobial and antitumor agents. Alex. J. Pharm. Sci., 14, 161-166 (2000)
  13. Kimura, M., Okabayashi, I., and Kato, A., Acridine derivatives. III. Preparation and antitumor activity of the novel acridinyl-substituted uracils. Chem. Pharm. Bull.,37, 697-701 (1989) https://doi.org/10.1248/cpb.37.697
  14. Mir, I., Siddiqui, M. T., and Cormie, A. M., Antituberculosis agents. V: Alpha-[5-(5-nitro-2-furyl)-1,3,4-oxadiazol-2-ylthio] acethydrazide and related compounds. J. Pharm. Sci., 80, 548-550 (1991) https://doi.org/10.1002/jps.2600800610
  15. O'Brien, R. J. and Nunn, P. P., The need for new drugs against tuberculosis. Obstacles, opportunities and next steps. Am. J. Respir. Crit. Care Med., 163, 1055-1058 (2001) https://doi.org/10.1164/ajrccm.163.5.2007122
  16. Omar, M. T. and Hamouly, W. S., Synthesis and antimicrobial evaluation of some new acridine derivatives. Al-Azhar Bull. Sci., 7, 153-159 (1996)
  17. Suling, W. J., Seitz, L. E., Pathak, V., Westbrook, L., Barrow, E. W., Zywno-Van-Ginkel, S., Reynolds, R. C., piper, J. R., and Barrow, W. W., Antimycobacterial activities of 2,4-diamino-5-deazapteridine derivatives and effects on mycobacterial dihydrofolate reductase. Antirnicrob. Ag. Chemother., 44, 2784-2793 (2000) https://doi.org/10.1128/AAC.44.10.2784-2793.2000
  18. Thiim, M. and Friedman, L. S., Hepatotoxicity of antibiotics and antifungals. Clin. Liver Dis., 7, 381-399 (2003) https://doi.org/10.1016/S1089-3261(03)00021-7
  19. Yamada, H., Nakahara, Y., Aoki, Y., Katoh, O., Hiura, K., Kuori, S., and Yamaguchi, M., Hospital-onset tuberculosis in compromised host. Intern. Med., 31, 740-745 (1992) https://doi.org/10.2169/internalmedicine.31.740
  20. Zachariah, R., Spielmann, M. P, Harries, A. D., and Salaniponi, F. L., Voluntary counselling, HIV testing and sexual behaviour among patients with tuberculosis in a rural district of Malawi. Int. J. Tuberc. Lung Dis., 7, 65-71 (2003)