DETERMINATION OF EFFICACY OF ISOXYL, A MYCOLIC ACID INHIBITOR, IN VITRO AGAINST MYCOBACTERIUM.TUBERCULOSIS STRAINS
DOI:
https://doi.org/10.20319/lijshls.2015.s11.0124Keywords:
MDR TB, Isoxyl, Mycolic Acid InhibitorAbstract
The enzymes involved in the biosynthetic pathways of the critical components including mycolic acids offer attractive and selective targets for the developments of novel anti-mycobacterial agents. Isoxyl (ISO), a mycolic acid inhibitor, is an old drug, which was used for the treatment of tuberculosis was evaluated. Determination of Minimum Inhibitory Concentration (MIC) pattern of clinical isolates of Mycobacterium tuberculosis (M. tuberculosis) to mycolic acid inhibitors namely ISO, Isoniazid (INH) and Ethionamide (ETH) by agar and broth dilution Method was done. Also the Minimum bactericidal concentrations were evaluated. Total 40 MDR and 20 susceptible strains of M tuberculosis were tested. The result of the MIC studies showed that ISO is capable of inhibiting the growth of M. tuberculosis in a range of 1-20μg/ml. Inhibitory activity of ISO was higher than activity of ETH in solid media. Amongst three antituberculosis drugs, INH showed highest bactericidal activity against M. tuberculosis strains followed by ETH. While ISO exhibited lowest bactericidal activity. Amongst, three drugs tested, ISO shows highest MBC/MIC ratio with lowest bactericidal activity. ISO showed significantly lower bactericidal activity against MDR strains than susceptible strains of M. tuberculosis. MBC/ MIC ratio of ISO was similar to MDR and susceptible strains of M. tuberculosis. Overall study implies that ISO may be suitable for the treatment of Tuberculosis, particularly multi-drug resistant kind.
References
Andrews, M. J. (2001). Determination of minimum inhibitory concentrations Suppl.S1. Journal of Antimicrobial Chemotherapy, 46, 5-16.
Balows, A., Hausler, W., Herrmann, K., Isenberg, H., & Shadomy, H. (1975) Paper presented at the American Society For Microbiology, Washington DC.
Brennan, P. J. (2002). Plenary lecture, Current developments in drug Discovery for Tuberculosis. Targeting Cell wall Biogenesis. Introduction symposium on current developments in drug discovery for tuberculosis, 5-6.
Chopra, P., Meena, L., & Singh, Y. (2003). New drug targets for Mycobacterium tuberculosis. Indian Journal of Medical Research, 117, 1-9.
Cruikshank, R., Duguid, J. P., & Swain, R. H. A. (1968). In Medical Microbiology (Vol. 53). Edinburgh and London: The ELBS and ES Livington Ltd.
David, H. L., Rastogi, N., Clavel-Seres, S., & Clement, F. (1988). Alterations on the outer wall architecture caused by the inhibition of mycoside C biosynthesis in Mycobacterium avium. Current microbiology, 17, 61-68.
Debarber, A. E., Mdluli, K., Basman, M. Bekkar, L. and Barry, C.E. (2000):. , U. S. A. 15 (97) 17: 9677–9682. (2000). Ethionamide activation and sensitivity in MDR M. tuberculosis. Proc Natl Acad Sci, 15(97)(17), 9677- 9682.
Diel, R., Loddenkemper, R., Zellweger, J., Sotgiu, G., D’Ambrosio, L., & Centis, R. (2013). Old ideas to innovate TB control: preventive treatment to achieve elimination. Eur. Respir., 42, 785–801.
Gallen, C. (1970). Isoxyl: a review of the results of its use over a five-year period in the tuberculosis field service of a large urban area. Antibitics and Chemotherapy, 16(2),139-48
Hawkins, J. E., Wallace Jr, R. J., & Brown, B. A. (1991). Antibacterial susceptibility tests: Mycobacteria. In Manual of Clinical Microbiology, 5th Edn, Balows A, Hausler WJ, Herrmann KL, Isenberg HD and Shadomy HJ, Eds. Am Society For Microbilogy, Washington DC. 1138-52.
Heifets, L. (1991). Drug susceptibility in the chemotherapy of mycobacterial infections. Boca Raton, Fla: CRC Press.
Hekking, A., & De Voogd, K. (1970). Clinical Data on 4-4′ Diisoamyloxythiocarbanilide (Isoxyl). Antibitics and Chemotherapy, 16(2),128-35
Lienhardt, C. (2012). New drugs for the treatment of tuberculosis: needs, challenges, promise and prospects for the future. J. Infect. Dis. , 205, S241–S249.
Lord. (1966). Sensitivity to Thiocarlide and thiacetazone of far eastern strains of M.tuberculosis. Tubercle, 47, 400.
Matlola, N. M., Steel, H. C., & Anderson, R. (2001). Antimycobacterial action of B4128, a novel tetramethylpiperidyl-substituted phenazine. J. of Antimicrob. Chemoth., 47, 199-202.
Meissner, G., & Stottmeier, D. (1965). Die Empfindlichkeit der Mycobakterien für 4-4′-Diisoamyloxythiocarbanilid (Isoxyl) und ihre Bestimmung auf Löwenstein-Jensen-Nährboden. Beiträge zur Klinik und Erforschung der Tuberkulose und der Lungenkrankheiten, 130(4), 289-295.Middlebrook, G. (1952). Sterilization of tubercle bacilli by isonicotinic acid hydrazine and the incidence of variants resistant to the drug in vitro. Am Rev Tuberc, 65, 765.
Mitchison, D. (1979). Basic mechanisms of chemotherapy. CHEST Journal, 76(6_Supplement), 771-781.
Mitra, P. P. (2012). Drug discovery in tuberculosis: a molecular approach. Indian J. Tuberc, 59, 194–206.
Offen, H. (1988). Thiomides:ethionamide , protionamide,. In K. Bartmann (Ed.), Antituberculosis Drugs (pp. 167). Berlin: Springer Verlg.
Phetsuksiri, B., Baulard, A. R., Cooper, A. M., Minnikin, D. E., Douglas, J. D., Besra, G. S., & Brennan, P. J. (1999). Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis. Antimicrobial agents and chemotherapy, 43(5),
-1051.
Raviglione, M., Marais, B., Floyd, K., Lonroth, K., Getahun, H., & Migliori, G. B. (2012). Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet, 379, 1902–1913.
Reddy, V. M., Nadadhur, G., Daneluzzi, D., Dimora, V. and Gangadharam, P.R.J. (1995). Antimycobacterial activity of new Rifamycin derivative 3-(4-cinnamylpiperazinyl Iminomethyl Rifamycin SV (T9). Antimicrob Agents Chemother, 39(10), 2320-2324.
Robinson, O., & Hunter, P. A. (1966). Absorption and excretion studies with thiocarlide (4′ 4- diisoamyloxythiocarbanilide) in man. Tubercle, 47(2), 207-213.
Schmid, C. (1970). Clinical experience in cases of primary tuberculosis with tuberculostaticum isixyl. Antibiot chemother, 16, 108-116.
Siddiqui, S. H., Libonati, J.P. and Middlebrook, G. (1981). Evaluation of a rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol, 13, 908-912.
Tischer, R. (1966). Monotherapie mit isoxyl/DAT bei tuberculose-asylierungfallen. Prax Pnemoniol: , 202.
Tomioka, H., Saito, H., Fujii, K., Sato, K., & Hidaka, T. (1993). In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method. Antimicrobial agents and chemotherapy, 37(1), 67-70.
Urbancik, B. (1970). Clinical experiences with thiocarlide ( Isoxyl). Antibiot Chemother, 16, 117-123.
Vestal, A. L. (1975). Procedures for the isolation and identification of Mycobacteria. Atlanta center for disease control.
Winder, F. G. (1982). Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of the mycobacteria. The biology of the mycobacteria, 1, 353-438.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2015 Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright of Published Articles
Author(s) retain the article copyright and publishing rights without any restrictions.
All published work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.