2-Amino-4-arylthiazole Derivatives as Anti-giardial Agents: Synthesis, Biological Evaluation and QSAR Studies

• Autorzy: Raul Mocelo-Castell , Carlos Villanueva-Novelo , David Cáceres-Castillo , Ruben M. Carballo , Ramiro F. Quijano-Quiñones , Mariana Quesadas-Rojas , Zulema Cantillo-Ciau , Roberto Cedillo-Rivera , Rosa E. Moo-Puc , Laila M. Moujir , Gonzalo J. Mena-Rejón
• Języki publikacji: EN

Abstrakty

EN

A series of seven 2-amino-4-arylthiazoles were prepared following Hantzsch’s modified method under microwave irradiation. A set of 50 derivatives was obtained and the in vitro activity against Giardia intestinalis was evaluated. The results on the biological activity revealed that, in general, the N-(5-bromo-4-aryl-thiazol-2-yl)-acetamide scaffold showed high bioactivity. In particular, compounds 6e (IC50 = 0.39 μM) and 6b (IC50 = 0.87 μM) were found to be more potent than the positive control metronidazole. Citoxicity and acute toxicity tests performed showed low toxicity and high selectivity of the most active compounds (6e SI = 139, 6b SI = 52.3). A QSAR analysis was applied to a data set of 37 obtained 2-amino-4-arylthiazoles derivatives and the best model described a strongly correlation between the anti-giardiasic activity and molecular descriptors as E2M, RDF115m, F10, MATS6v, and Hypnotic-80, with high statistical quality. This finding indicates that N-substituted aminothiazole scaffold should be investigated for the development of highly selective anti-giardial agent.

EN

Słowa kluczowe

EN

2-amino-4-arylthiazole; Anti-protozoal activity; Giardia intestinalis; QSAR

• Czasopismo: Open Chemistry
• Rocznik: 2015
• Tom: 13
• Numer: 1

Daty

otrzymano

2014-11-04

zaakceptowano

2015-06-20

online

2015-09-07

Twórcy

autor

Raul Mocelo-Castell

• Facultad de Química, Universidad de La Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revolución, CP 1040 Ciudad de La Habana, Cuba

autor

Carlos Villanueva-Novelo

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

David Cáceres-Castillo

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

Ruben M. Carballo

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

Ramiro F. Quijano-Quiñones

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

Mariana Quesadas-Rojas

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

Zulema Cantillo-Ciau

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

autor

Roberto Cedillo-Rivera

• Unidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad, Centro Médico Ignacio García Téllez IMSS, Calle 41, N. 439, Col. Industrial, Mérida, Yucatán, 97150 México

autor

Rosa E. Moo-Puc

• Unidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad, Centro Médico Ignacio García Téllez IMSS, Calle 41, N. 439, Col. Industrial, Mérida, Yucatán, 97150 México

autor

Laila M. Moujir

• Departamento de Microbiología y Biología Celular, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206, Tenerife, Islas Canarias, España

autor

Gonzalo J. Mena-Rejón

• Laboratorio de Química Farmacéutica, Facultad de Química, Universidad Autónoma de Yucatán,
  Calle 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, México

Bibliografia

• [1] Cotton J.A., Beatty J.K., Buret A.G., Host parasite interactions and pathophysiology in Giardia infections, Int. J. Parasitol., 2011, 41, 925-933.[WoS][Crossref]
• [2] (a) Escobedo A.A., Almirall P., Robertson L.J., Franco R.M.B., Hanevik K., Mørch K., Cimerman S. Giardiasis: the ever-present threat of a neglected disease, Infect. Disord.-Drug Targets., 2010, 10, 329-348. (b) Roxström-Lindquist, K., Palm, D., Reiner, D., Ringqvist, E., Svärd, S.G., Giardia immunity - an update, Trends Parasitol., 2006, 22, 26-31.
• [3] Savioli L., Smith H., Thompson A., Giardia and Cryptosporidium join the ’Neglected Diseases Initiative’, Trends. Parasitol., 2006, 22, 203-208.[Crossref]
• [4] Pasupuleti V., Escobedo A.A., Deshpande A., Thota P., Roman Y., Hernandez A.V., Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials, PLoS Negl. Trop. Dis., 2014, http://journals.plos.org/ plosntds /article?id=10.1371 /journal.pntd.0002733.
• [5] Löfmark S., Edlund C., Nord C.E., Metronidazole Is Still the Drug of Choice for Treatment of Anaerobic Infections, Clin. Infect. Dis., 2010, 50, S16-S23.[WoS]
• [6] (a) Ortega Y., Adam R., Giardia: Overview and update, Clin. Infect. Dis, 1997, 25, 545-549. (b) Müller J., Rühle G., Müller N., Rossignol J.-F., Hemphill A., In vitro effects of thiazolides on Giardia lamblia WB clone C6 cultured axenically and in coculture with Caco2 cells, Antimicrob. Agents Chemother., 2006, 50, 162-170. (c) Singh S., Bharti N., Mohapatra P.P., Chemistry and Biology of Synthetic and Naturally Occurring Antiamoebic Agents, Chem. Rev., 2009, 109, 1900-1947.[Crossref]
• [7] (a) Purohit, V., Basu, A.K., Mutagenicity of nitroaromatic compounds, Chem. Res. Toxicol., 2000, 13, 673-692. (b) Lopez-Nigro M.M., Palermo A.M., Mudry M.D., Carballo M.A., Cytogenetic evaluation of two nitroimidazole derivatives, Toxicol. In Vitro, 2003, 17, 35-40. (c) El-Nahas F.A., El-Ashmawy I.M., Reproductive and cytogenetic toxicity of metronidazole in male mice, Basic Clin. Pharmacol.Toxicol., 2004, 94, 226-231.
• [8] Mineno T., Avery M.A., Giardiasis: Recent progress in chemotherapy and drug development, Curr. Pharm. Des., 2003, 9, 841-855.[Crossref]
• [9] Upcroft P., Upcroft J.A., Drug targets and mechanisms of resistance in anaerobic protozoa. Clin. Microbiol. Rev., 2001, 14, 150-164.[Crossref]
• [10] Tejman-Yarden N., Miyamoto Y., Leitsch D., Santini J., Debnath A., Gut J., et al., A Reprofiled Drug, Auranofin, Is Effective against Metronidazole-Resistant Giardia lamblia, Antimicrob. Agents Chemother., 2013, 57, 2029-2035.
• [11] Fox L.M., Saravolatz L.D., Nitazoxanide: A new thiazolide antiparasitic agent, Clin. Infect. Dis., 2005, 40, 1173-1180.[Crossref]
• [12] Rossigno J.F., Lopez-Chegne N., Julcamoro L.M., Carrion M.E., Bardin M.C., Nitazoxanide for the empiric treatment of pediatric infectious diarrhea, Trans. R. Soc. Trop. Med. Hyg., 2012, 106, 167-173.[Crossref]
• [13] Eckmann L., Watkins R., Treatment of Giardiasis: Current Status and Future Directions, Curr. Infect. Dis. Rep., 2014, 16, 396-403.[WoS]
• [14] For recent papers on antimicrobial activity, see: (a) Annadurai S., Martinez R., Canney D.J., Eidem T., Dunman P.M., Abou-Gharbia M., Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA, Bioorg. Med. Chem. Lett., 2012, 22, 7719-7725. (b) Roy K.K., Singh S., Sharma S.K., Srivastava R., Chaturvedi V., Saxena A.K., Synthesis and biological evaluation of substituted 4-arylthiazol-2-amino derivatives as potent growth inhibitors of replicating Mycobacterium tuberculosis H37RV, Bioorg. Med. Chem. Lett., 2011, 21, 5589-5593. (c) Liaras K., Geronikaki A., Glamočlija J., Cirić A., Soković M., Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation, Bioorg. Med. Chem. Lett., 2011, 19, 3135-3150. (d) Alam M.S., Liu L., Lee Y.-E., Lee D.-U, Synthesis, Antibacterial Activity and Quantum-Chemical Studies of Novel 2-Arylidenehydrazinyl-4-arylthiazole Analogues, Chem. Pharm. Bull., 2011, 5, 568-573. For antifungal activity, see: (e) Yu H., Shao L., Fang J.J., Synthesis and biological activity research of novel ferrocenyl-containing thiazole imine derivatives, J. Organomet. Chem., 2007, 692, 991-996. (f) Shao L, Zhou X, Zhang Q., Liu J.B., Jin Z., Fang J.X., Synthesis, structure, and biological activity of novel 1H-1,2,4-Triazol-1-yl-thiazole derivatives, Synth. Commun., 2007, 37, 199-207. For antiviral activity, see: (g) Stachulski A.V., Pidathala C., Row E.C., Sharma R., Berry N.G., Iqbal M., et al. Thiazolides as Novel Antiviral Agents. 1. Inhibition of Hepatitis B Virus Replication, J. Med. Chem., 2011, 54, 4119-4132. (h) Liu Y., Zhang L., Gong J., Fang H., Liu A., Du G., et al., Design, synthesis, and biological activity of thiazole derivatives as novel influenza neuraminidase inhibitors, J. Enz. Inhib. Med. Chem., 2011, 26, 506-513.
• [15] (a) Berg M., Van der Veken P., Joossens J., Muthusamy V., Breugelmans M., Moss C. X., et al., Design and evaluation of Trypanosoma brucei metacaspase inhibitors, Bioorg. Med. Chem. Lett., 2010, 20, 2001-2006. (b) Maya J. D., Morello A., Repetto Y., Rodríguez A.,Puebla P., Caballero E., et al., Trypanosoma cruzi: Inhibition of parasite growth and respiration by oxazolo(thiazolo)pyridine derivatives and its relationship to redox potential and lipophilicity, Exp. Parasitol., 2001, 99, 1-6. (c) Branowska D., Farahat A.A., Kumar A., Wenzler T., Brun R., Liu Y., et al., Synthesis and antiprotozoal activity of 2,5-bis[amidinoaryl]thiazoles, Bioorg. Med. Chem. Lett., 2010, 18, 3551-3558.
• [16] (a) Walker R.G., Thomson G., Malone K., Nowicki M.W., Brown E., Blake D., et al., High Throughput Screens Yield Small Molecule Inhibitors of Leishmania CRK3:CYC6 Cyclin-Dependent Kinase, PLoS Negl. Trop. Dis., 2011, http://journals.plos.org/plosntds/ article?id=10.1371/journal.pntd.0001033. (b) Delmas, F., Avellaneda, A., Di Giorgio, C., Robin, M., De Clercq, E., Timon-David, P., et al., Synthesis and antileishmanial activity of (1,3-benzothiazol-2-yl) amino-9-(10H)-acridinone derivatives, Eur. J. Med. Chem., 2004, 39, 685-690.
• [17] Karade H.N., Acharya B.N., Sathe M., Kaushik M.P., Design, synthesis, and antimalarial evaluation of thiazole-derived amino acids, Med. Chem. Res., 2008, 17, 19-29.[WoS][Crossref]
• [18] (a) Hencken C.P., Jones-Brando L., Bordón C., Stohler R., Mott B. T., Yolken R., et al., Thiazole, Oxadiazole, and Carboxamide Derivatives of Artemisinin are Highly Selective and Potent Inhibitors of Toxoplasma gondii, J. Med. Chem., 2010, 53, 3594-3601. (b) Tapia R.A., Alegria L., Pessoa C.D., Salas C., Cortés M.J., Valderrama J.A., et al., Synthesis and antiprotozoal activity of naphthofuranquinones and naphthothiophenequinones containing a fused thiazole ring, Bioorg. Med. Chem. Lett., 2003, 11, 2175-2182.
• [19] (a) Stadelmann B., Scholl S., Müller J., Hemphill A.J., Application of an in vitro drug screening assay based on the release of phosphoglucose isomerase to determine the structure-activity relationship of thiazolides against Echinococcus multilocularis metacestodes J. Antimicrob. Chemother., 2010, 65, 512-519. (b) Esposito M., Moores S., Naguleswaran A., Mu J., Hemphill A., Induction of tachyzoite egress from cells infected with the protozoan Neospora caninum by nitro- and bromo-thiazolides, a class of broad-spectrum anti-parasitic drugs, Int. J. Parasitol. 37, 1143 (2007).
• [20] Morales-Bonilla P., Perez-Cardeña A., Quintero-Marmol E., Arias-Tellez J.L., Mena-Rejon G.J., Preparation, antimicrobial activity and toxicity of 2-amino-4-arylthiazole derivatives, Heteroatom Chem., 2006, 17, 254-260.[Crossref]
• [21] Wavefunction, Inc. Irvine, CA. Spartan’06.
• [22] Gaussian 09, Revision A.1, Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R., et al., Gaussian, Inc., Wallingford CT, 2009.
• [23] Tomasi J., Mennucci B., Cammi R.,Quantum mechanical continuum solvation models, Chem. Rev., 2005, 105, 2999-3093.[Crossref]
• [24] Lee C., Yang W., Parr, R.G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys. Rev. B., 1996, 37, 785.
• [25] Livingstone D., Analysis for chemists, Oxford University Press, UK, 1995.
• [26] (a) Ward Jr J.H., Hierarchical grouping to optimize an objective function, J. Am. Stat. Assoc., 1963, 58, 236-244. (b) Dearden J.C., Cronin M.T.D., Kaiser K.L.E., How not to develop a quantitative structure–activity or structure–property relationship (QSAR/QSPR), SAR and QSAR Environ. Res., 2009, 20, 241-266.[Crossref]
• [27] Systat for Windows, versión 12.02.00; Systat software, Inc.: 2007.
• [28] (a) Golbraikh A., Shen M., Xiao Z., Xiao Y.D., Lee K.H., Tropsha A., Rational selection of training and test sets for the development of validated QSAR models, J. Comput. Aided Mol. Des., 2003, 17, 241-253. (b) Hawkins D.M., Basak S.C., Mills D., Assessing model fit by cross-validation, J. Chem. Inf. Comput. Sci., 2003, 43, 579-586.
• [29] Cáceres-Castillo D., Carballo R.M., Tzec-Interián J.A., Mena-Rejón G., Solvent-free synthesis of 2-amino-4-arylthiazoles under microwave irradiation, Tetrahedron Lett., 2012, 53, 3934-3936.[WoS][Crossref]
• [30] Mena-Rejón G.J., Pérez-Espadas A.R., Moo-Puc R. E., Cedillo-Rivera R., Bazzocchi I.L., Jiménez-Diaz I.A., et al., Antigiardial Activity of Triterpenoids from Root Bark of Hippocratea excelsa, J. Nat. Prod., 2007, 70, 863-865.[Crossref]
• [31] Müller J., Wastling J., Sanderson S., Müller N., Hemphill A., A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and other thiazolides, Antimicrob. Agents Chemother., 2007, 51, 1979-1986.
• [32] (a) Esposito M., Stettler R., Moores S.L., Pidathala C., Müller N., Stachulski A., et al., In vitro efficacies of nitazoxanide and other thiazolides against Neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group, Antimicrob. Agents Chemother., 2005, 49, 3715-3723. (b) Cortes, H.C.E., Mueller, N., Esposito, M., Leitão, A., Naguleswaran A., Hemphill A., In vitro efficacy of nitro-and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells, Parasitology., 2007, 134, 975-985.
• [33] Müller J., Rühle G., Müller N., Rossignol J.-F., Hemphill A., In vitro effects of thiazolides on Giardia lamblia WB clone C6 cultured axenically and in coculture with Caco2 cells, Antimicrob. Agents Chemother., 2006, 50, 162-170.
• [34] Wilcken R., Zimmermann M.O., Lange A., Joerger A.C., Boeckler F.M., Principles and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology, J. Med. Chem., 2013, 56, 1363-1388.[WoS][Crossref]
• [35] Pink A.R., Hudson M-A., Mouriès K., Bendig M., Opportunities and Challenges in Antiparasitic Drug Discovery, Nat. Rev. Drug. Discov., 2005, 4, 727-740.[Crossref]
• [36] dos Santos P.R., Roesch Ely M., Dumas F., Moura S., Synthesis, structural characterization and previous cytotoxicity assay of Zn(II) complex containing 1,10-phenanthroline and 2,2’-bipyridine with valproic acid, Polyhedron, 2015, 90, 239-244.
• [37] Lu Y., Shi T., Wang Y., Yang H., Yan X., Luo X., et al., Halogen Bonding-A Novel Interaction for Rational Drug Design?, J. Med. Chem., 2009, 52, 2854-2862[Crossref][WoS]
• [38] Topliss J.G., Costello R.J., Chance correlations in structure-activity studies using multiple regression analysis, J. Med. Chem., 1972, 15, 1066-1068.[Crossref]
• [39] Hemmer M.C., Steinhauer V., Gasteiger J., Deriving the 3D structure of organic molecules from their infrared spectra, Vib. Spectrosc., 1999, 19, 151-164.
• [40] Nowaczyk A., Kulig K., Malawska B., 1-(3-(4-Arylpiperazin-1-yl)-propyl)-Pyrrolidin -2-one Derivatives as α1-Adrenoceptor Antagonists: A QSAR Study, QSAR Comb. Sci., 2009, 28, 979-988.[WoS]
• [41] Ghose A.K., Viswanadhan V.N., Wendoloski J.J., A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases, Comb. Chem., 1999, 1, 55-68.
• [42] Li J., Li S., Baia Ch., Liu H., Gramatica P., Structural requirements of 3-carboxyl-4(1H)-quinolones as potential antimalarials from 2D and 3D QSAR analysis, J. Mol. Graph. Mod., 2013, 44, 266–277.[Crossref]
• [43] Pérez González M., Terán C., Teijeira M., Morales Helguera A., Radial distribution function descriptors: an alternative for predicting A2 A adenosine receptors agonists, Eur. J. Med. Chem., 2006, 41, 56-62.[Crossref]
• [44] Asadabadi E.B., Abdolmaleki P., Barkooie S.M.H., Jahandideh S., Rezaei M.A., A combinatorial feature selection approach to describe the QSAR of dual site inhibitors of acetylcholinesterase, Comp. Biol. Med., 2009, 39, 1089-1095. [Crossref]

Identyfikatory

DOI

10.1515/chem-2015-0127