EVALUATION OF A GROUP OF PYRROLE DERIVATIVES AS TUBERCULOSTATIC AGENTS
Abstract: This research aims to contribute to the global search for more effective tuberculostatics that has been triggered by recent outbreaks of tuberculosis. A group of pyrrole-containing derivatives are designed and theoretically elucidated. The identification of the pharmacophore group using the PharmaGist webserver is attempted. Also, the corresponding drug-like properties of the tested compounds are evaluated, together with their possible toxicity risks. The pharmacokinetic behavior of the structures is predicted, based on the Lipinski’s Rule of Five. The effects of some structural parameters are tested. In addition, in vitro evaluations of the anti-tubercular activity against Mycobacterium tuberculosis H37Rv are performed, with compound GA-9 registering the highest activity.
APA: Who | Tuberculosis. (2017.). Retrieved from http://www.who.int/mediacentre/factsheets/fs104/en/?ncid=newsltushpm-g00000003)
APA: Who/europe | Bulgaria. (n.d.). Retrieved from http://www.euro.who.int/en/health-topics/communicable-diseases/tuberculosis/coun
Biava, M., Porretta, G. C., Poce, G., De Logu, A., Saddi, M., Meleddu, R., Manetti, F., De Rossi, E., & Botta M. (2008). 1,5-Diphenylpyrrole Derivatives as Antimycobacterial Agents. Probing the Influence on Antimycobacterial Activity of Lipophilic Substituents at the Phenyl Rings. J. Med. Chem., 51 (12), 3644–3648.
Biava, M., Porretta, G., Deidda, D., Pompei, R., & Tafi, A. (2004). Antimycobacterial compounds. New pyrrole derivatives of BM212. Bioorganic & Medicinal Chemistry, 12, 1453-1458.
Bijev, A. (2006). New hydrazones as pyrrole derivatives with higher inhibitory activity against Mycobacterium tuberculosis. Lett Drug Des Discov, 3(7), 506-512.
Bijev, A. (2008a). Synthesis, in vitro evaluations and structure-activity assessment of pyrrole hydrazones. Lett Drug Des Discov, 5(1), 15-24.
Bijev, A., & Georgieva, M. (2010). Pyrrole-Based Hydrazones Synthesized and Evaluated In Vitro as Potential Tuberculostatics. Letters in Drug Design & Discovery, 7 (6), 430-437.
Bijev, А. (2008b). Synthesis and in vitro Evaluation of New Hydrazones as Pyrrole Derivatives with Anti-tubercular Activity. Arzneim-Forsch/Drug Res.
Collins, L., & Franzblau S. G. (1997). Microplate Alamar Blue Assay versus ВАСТEС 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob Agents Chemother, 41, 1004-1009.
Deidda, D., Lampis, G., Fioravanti, R., Biava, M., & Porretta, G.C. (1998). Bactericidal activities of the pyrrole derivative BM 212 against multidrug-resistant and intramacro-phagic Mycobacterium tuberculosiss trains. Antimicrob Agents Chemother, 42, 3035–3037.
Georgieva, M., Bijev, A., & Nencheva, I. (2011). Isolation and characterization of isomers of pyrrole-hydrazones with possible tuberculostatic activity. Comparison of methods for separation. Pharmacia, LVIIІ, 26-31.
Georgieva, M., Bijev, A., & Prodanova, P. (2010). Synthesis and comparative study of tuberculostatic activity of pyrrole-based hydrazones related to structural variations. Pharmacia, 57 (1-4), 3-14.
http://www.euro.who.int/en/health-topics/communicable-diseases/tuberculosis/country-work/bulgaria/, Accessed on 15 January 2017.
http://www.who.int/mediacentre/factsheets/fs104/en/, Accessed on 15 January 2017.
Lessigiarska, I., Pajeva, I., Prodanova, P., Georgieva, M., & Bijev, A. (2012). Structure-activity relationships of pyrrole hydrazones as new anti-tuberculosis agents. Medicinal Chemistry Med Chem, 8 (3), 462-473.
Lipinski, C. A., Lombardo, F., Dominy, B.W., & Feeney, P. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. J. Adv. Drug Deliv. Rev., 23, 3.
Lipinski, C. A., Lombardo, F., Dominy, B.W., & Feeney, P.J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev, 46, 3-26.
Molinspiration Cheminformatics, http://www.molinspiration.com/ (accessed on Jan17th, 2016).
Petrović, V. P., Simijonović, D., Živanović, M. N., Košarić, J. V., Petrović, Z. D., Marković, S., & Marković, S. D. (2014). Vanillic Mannich bases: synthesis and screening of biological activity. Mechanistic insight into the reaction with 4-chloroaniline. RSC Adv., 4, 24635-24644.
Poce, G., Bates, R. H., Alfonso, S., Cocozza, M., Porretta, G. C., Ballell, L., Rullas, J., Ortega, F., De Logu, A., Agus, E., La Rosa, V., Pasca, M. R., De Rossi, E., Wae, B., Franzblau, S. G., Manetti, F., Botta, M. & Biava M. (2013). Improved BM212 MmpL3 Inhibitor Analogue Shows Efficacy in Acute Murine Model of Tuberculosis Infection, PLoS One, 8 (2), e56980.
Sander, Thomas Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, 4123 Allschwil, Switzerland, Retrieved January, 16, 2017 from http://www.organic-chemistry.org/prog/peo/.
Sander, Thomas Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, 4123 Allschwil, Switzerland, Retrieved January, 16, 2017 from http://www.organic-chemistry.org/prog/peo/Drug-likeness.html.
Sander, Thomas Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, 4123 Allschwil, Switzerland, Retrieved January, 16, 2017 from http://www.organic-chemistry.org/prog/peo/drugScore.html.
Schneidman-Duhovny, D., Dror, O., Inbar, Y., Nussinov, R., & Wolfson H. J. (2008). PharmaGist: a webserver for ligand-based pharmacophore detection. Nucleic Acids. Research, 1–6
SRI International Screening Program on line: http://www.niaid.nih.gov/LabsAnd Resources/resources/dmid/pretheraagents/Pages/preclinexamples.aspx (accessed on 26 January 2010).
SRI International, Home page: http://www.sri.com (accessed on 26 January 2010).
Vladimirova, S., & Bijev, A. (2015). Synthesis of new derivatives of pyrrole tuberculostatics providing structural diversity. Pharmacia, 62(1), 3-8.
Zhao, Y. H., Abraham, M. H., Lee, J., Hersey, A., Luscombe, Ch. N., Beck, G., Sherborne, B., & Cooper, I. (2002) Rate-limited steps of human oral absorption and QSAR studies. Pharm. Res., 19, 1446-1457.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (Creative Commons Attribution License 3.0 - CC BY 3.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
email@example.com, www.iseic.cz, ojs.journals.cz