SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF PIPERIDINE AND MORPHOLINE 1, 8 NAPHTHYRIDINE ANALOGUES
Objective: The search for new, potentially useful antimycobacterial agents. In continuation with our previous screening for the discovery of novel drugs for tuberculosis, a new series of 1,8-naphthyridines derivatives were synthesized and evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis H37Rv.
Methods: Several 4-morpholinomethyl-1.8-naphthyridine derivatives have been synthesized in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimycobacterial activity. The growth was monitored radiometrically inÂ 7H12 brothÂ with theÂ BACTECÂ 460Â TBÂ system. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated â‰¥ 90% growth inhibition in the primary screening.
Results: The obtained data suggested that all compounds showed significant activity against Mycobacterium tuberculosis H37Rv compared to the standard reference drug. Analogues (6-11) having heterocyclic groups in position 7 were the most potent of those we tested.
Conclusion: These findings clearly identify the 1,8-naphthyridine analogue (10) with a 6-amino-2-(4'-methoxy benzylamine-4-morpholinomethyl-7-morpholino-substituent as promising anti-tubercular agents possessing significant activity against Mycobacterium tuberculosis H37Rv
2. Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet 2003;362:887-99.
3. Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolones, tuberculosis, and resistance. Lancet Infect Dis 2003;3:432-42.
4. Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis 2006;194:479-85.
5. Ozadali K, Tan OU, Yogeeswari P, Dharmarajan S, Balkan A. Synthesis and antimycobacterial activities of some new thiazolyl hydrazone derivatives. Bioorg Med Chem Lett 2014;24:1695-7.
6. Kurniawati F, Sulaiman SAS, Gillani SW. Study on drug-resistant tuberculosis and tuberculosis treatment on patients with drug-resistant tuberculosis in chest clinic outpatient department. Int J Pharm Pharm Sci 2012;4:733-7.
7. Siddiqui S, Baig MMA, Jaffer S, Ansari SFR. Study on prevalence of adverse drug reactions in patients suffering from tuberculosis in a tertiary care hospital. Int J Pharm Pharm Sci 2016;8:375-7.
8. Global alliance for TB drug development; 2008. Available from: http://www.tballiance.org/home/home.php. [Last accessed on 10 May 2016]
9. Dorman SE, Chaisson RE. From magic bullets back to the magic mountain: the rise of extensively drug-resistant tuberculosis. Nat Med 2007;13:295-8.
10. Hussein MA, Aboul-fadi T, Hussein A. Synthesis and antitubercular activity of some mannich bases derived from isatin isonicotinic acid hydrazine. Bull Pharm Sci Assiut Univ 2005;28:131-6.
11. Sriram D, Aubry A, Yogeeswari P, Fisher LM. Gatifloxacin derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase. Bioorg Med Chem Lett 2006;16:2982-5.
12. Mukesh M, Manju P, Sabitha M. Structural model of the alpha phosphoglucomutase: a promising target for the treatment of Mycobacterium tuberculosis. Int J Pharm Pharm Sci 2013;5:107-14.
13. Perumal P, Pandey VP, Parasuraman P. Docking studies on antimicrobial peptides related to apidaecin-IA and human histatin against glutamine synthase and RNA polymerase in Mycobacterium tuberculosis. Asian J Pharm Clin Res 2014;7:195-201.
14. Migliori GB, Ortmann J, Giradi E, Besozzi G, Lange C, Cirillo DM, et al. Extensively drug-resistant tuberculosis, Italy, and Germany. Emerging Infect Dis 2007;13:780-2.
15. Badawneh M, Bellini L, Cavallini T, Aljamal JA, Manera C, Saccomanni G, et al. Synthesis of 3-or 4-phenyl-1,8-napththyridine derivatives and evaluation of antimycobacterial and antibacterial activity. Farmaco 2003;58:859-66.
16. Badawneh M, Aljamal JA. Synthesis of 4-morpholinomethyl-1,8-naphthyridine derivatives with antimycobacterial activity. Alex J Pharm Sci 2003;17:105-9.
17. Middlebrook G, Reggiardo Z, Tigertt WD. Automatable radiometric detection of growth of Mycobacterium tuberculosis in selective media. Am Rev Respir Dis 1977;115:1067-9.
18. Aljamal JA, Badawneh M. Characterization of the biochemical effects of new 1,8-naphthyridine derivatives, Î²-receptor antagonists, in ventricular myocytes. Arch Pharm Pharm Med Chem 2003;336:285-92.
19. Collins LA, Franzblau SG. Microplate alamar blue assay versus BACTEC 460 system for high throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium Avium. Antimicrob Agents Chemother 1997;41:1004-9.
20. Badawneh M, Manera C, Mori C, Saccomanni G, Ferrarini PL. Synthesis of variously substituted 1,8-naphthyridine derivatives and evaluation of their antimycobacterial activity. Framaco 2002;57:631-9.
21. Orme I, Secrist J, Anathan S, Kwong C, Maddry J, Reynolds R, et al. Search for new drugs for the treatment of tuberculosis. Antimicrob Agents Chemother 2001;45:1943-6.