Synthesis, antimicrobial evaluation and in silico studies of the (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles


  • Josefa Aqueline da Cunha Lima Universidade Federal Rural de Pernambuco
  • Erick Caique Santos Costa Universidade Federal de Campina Grande
  • Giselle Barbosa Bezerra Universidade Federal Rural de Pernambuco
  • Jadson de Farias Silva Universidade Federal Rural de Pernambuco
  • Rodrigo Ribeiro Alves Caiana Universidade Federal de Campina Grande
  • Joao Rufino de Freitas Filho Universidade Federal Rural de Pernambuco
  • Juliano Carlo Rufino Freitas Universidade Federal de Campina Grande



Antimicrobial activity, In silico, Oxadiazole. Synthesis.


In recent years, investigations in the field of oxadiazoles have been intensified due to their numerous therapeutic uses. Oxadiazoles are a class of compounds that exhibit several biological applications, citing antimicrobial, anti-inflammatory, anti-diabetic, anthelmintic, anti-tumor, among others. Encouraged by the biological potential of oxadiazoles, were carried out synthesis, antimicrobial evaluation and in silica studies of five (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles. In this way, (Z)-aryl-N'-hydroxybenzimidamides and ethyl (E)-cinnamate were synthesized, which were subjected to an O-acylamidoxime reaction after by dehydration using microwave irradiation to form the oxadiazole nucleus. The compounds were characterized by spectroscopic techniques, while in vitro antimicrobial activity was evaluated against S. aureus, E. faecalis, E. coli, P. aeruginosa, and against the fungus C. utilis using the microplate microdilution method. Thus, (Z)-aryl-N'-hydroxybenzimidamides, ethyl (E)-cinnamate, and (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles were synthesized with yields ranging from moderate to good. The (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles exhibited a reduced spectrum of action, which were active against the bacterium P. aeruginosa and for the fungus C. utilis.


Download data is not yet available.


ANDRADE, D., FREITAS FILHO, J.R. and FREITAS, J.C.R. Aplicação de amidoximas como catalisadores da reação de alilação por aliltrifluoroborato de potássio em meio bifásico. Quimica Nova. 2016, 39(10), 1225-1235.

BARREIRO, E.J. and FRAGA, C.A.M. Química Medicinal: As bases moleculares da ação dos fármacos. 3rd ed. Porto Alegre: Artmed, 2014.

BARROS, C.J.P., FREITAS, J.J.R., OLIVEIRA, R.N. and FREITAS FILHO, J.R. Synthesis of amidoximes using an efficient and rapid ultrasound method. Journal of the Chilean Chemical Society. 2011, 56, 721-722.

BARROS, C.J.P., et al. Convenient synthesis and cytotoxic activity of 3-aryl-5-pentyl-1,2,4-oxadiazoles from carboxylic acid esters and arylamidoximes under solvent-free conditions. Journal of the Chilean Chemical Society. 2014, 59(1), 2359-2362.

BELETSKII, E.V., IGNATENKO, O.A., KUZNETSOV, M.A. and SELIVANOV, S.I. Oxidative addition of N-aminophthalimide to styryl-1,2,4-oxadiazoles. Russian Journal of Organic Chemistry. 2010, 46(5), 678-684.

BROTSCHI, C., et al. Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis, Structure–Activity Relationships, and Sleep‐Promoting Properties in Rats. ChemMedChem. 2019, 14, 1257-1270.

CUNHA, F.S. and AGUIAR, A.P. Síntese e Bioatividade de 1,2,4-Oxadiazóis. Revista Virtual Química. 2015, 7(6), 2509-2530.

DAINA, A., MICHIELIN, O. and ZOETE, V. SwissADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports. 2017, 7(1), 42717.

DAINA, A., ZOETE, V. A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 2016, 11(11), 1117-1121.

DIGIANDOMENICO, A., et al. Protective activity of medi3902 for the prevention or treatment of lethal pneumonia and bloodstream infection caused by pseudomonas aeruginosa in rabbits. American Journal of Respiratory and Critical Care Medicine. 2017, 195, A2646-A2646.

DUVAL, R.E., GRARE, M. and DEMORÉ, B. Fight against antimicrobial resistance: we always need new antibacterials but for right bacteria. Molecules. 2019, 24(17), 3152-3160.

ESPINEL-INGROFF, A., et al. Quality Control and Reference Guidelines for CLSI Broth Microdilution Susceptibility Method (M38-A Document) for Amphotericin B, Itraconazole, Posaconazole, and Voriconazole. Journal of Clinical Microbiology. 2005, 43(10), 5243-5246.–5246

FAIZI, M., et al. Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists. Iranian Journal of Pharmaceutical Research. 2012, 11(1), 83-90.

GOLAN, D.E., TASHJIAN JUNIOR, A.H., ARMSTRONG, E.J. and ARMSTRONG, A.W. Princípios de farmacologia: a base fisiopatológica da farmacoterapia. 3rd ed. Rio de Janeiro: Guanabara Koogan, 2014.

GUIMARÃES, D.O., MOMESSO, L.S. and PUPO, M.T. Antibióticos: importância terapêutica e perspectivas para a descoberta e desenvolvimento de novos agentes. Química Nova. 2010, 33(3), 667-679.

IRFAN, M., ALAM, S., MANZOOR, N. and ABID, M. Effect of quinoline based 1,2,3-Triazole and its structural analogues on growth and virulence attributes of Candida albicans. PLoS One. 2017, 12(4), 1-23.

KNOP, L. B. and MARIA, D.A. Métodos substitutivos e a experimentação animal: um enfoque inovador. Revista da Sociedade Brasileira de Ciência em Animais de Laboratório. 2017, 4(2), 101-114.

LEE, H. and LEE, D.G. Novel Approach into Efficient Antifungal Drug Action. Journal of microbiology and biotechnology. 2018, 28(11), 1771-1781.

LI, Y., et al. Synthesis, insecticidal activity, and structure–activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings. Organic and Biomolecular Chemistry. 2013, 11(24), 3979-3988. 1477-0539

LIPINSKI, C.A. Lead and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies. 2004, 1(1), 337-341.

LIPINSKI, C.A., LOMBARDO, F., DOMINY, B.W. and FEENEY, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 1997, 23(1-3), 4-25.

MODA, T.L. Modelagem in silico de propriedades farmacocinéticas para a avaliação de candidatos a novos fármacos. 2011. São Carlos: Universidade de São Paulo, 2011.Tese de doutorado.

MORALES, G., PAREDES, A., SIERRA, P. and LOYOLA, L.A. Antimicrobial activity of three baccharis species used in the traditional medicine of northern Chile. Molecules. 2008, 13(4), 790-794.

MURRAY, P., ROSENTHAL, K.S. and PFALLER, M.A. Microbiologia Médica. 7th ed. Rio de Janeiro: Elsevier Brasil, 2015.

NEVES, P.R., MAMIZUKA, E.M., LEVI, C.E. and LICOPAN, N. Pseudomonas aeroginosas multirresistente: um problema endêmico no Brasil. Jornal Brasileiro de Patologia e Medicina Laboratorial. 2011, 47(4), 409-420.

OLIVEIRA, M.L.G. Avaliação in silico do potencial farmacológico e toxicológico de friedelanos, lupanos e derivados. Belo Horizonte: Universidade Federal de Minas Gerais, 2014. Tese de doutorado.

PANKRATEVA, V.E., et al. One-Pot Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles Using Catalytic System NaOH‒DMSO. Russian Journal of Organic Chemistry. 2018, 54(8), 1250-1255.

PAPA, E., ARNOD, J.A., SANGION, A. and GRAMATICA, P., 2017. In Silico Approaches for the Prediction of In Vivo Biotransformation Rates. In: ROY, K. Advances in QSAR Modeling. New York: Springer, pp. 425-451.

PERRIN, D.D. and AMAREGO, W.L.F. Purification of Laboratory Chemicals. Oxford: Pergamon Press, 1996.

PRESTINACI, F., PEZZOTTI, P. and PANTOSTI, P. Antimicrobial resistance: a global multifaceted phenomenon. Pathogens and Global Health. 2015, 109(7), 309-318.

RANG, H.P., RITTER, J.M., FLOWER, R.J. and HENDERSON, G. Farmacologia. 8th ed. Rio de Janeiro: Elsevier, 2016.

ROCHA, D.S., et al. Potential Antimicrobial and Chemical Composition of Essential Oils from Piper caldense Tissues. Journal of the Mexican Chemical Society. 2016, 60(3), 148-151.

ROSSITER, S.E., FLETCHER, M.H. and WUEST, W.M. Natural Products as Platforms to Overcome Antibiotic Resistance. Chemical Reviews. 2017, 117(19), 12415-12474.

RYU, H-C., HONG, Y-T. and KANG, S-K. Palladium-catalyzed Carbonylative Coupling of Hypervalent Iodonium Salts with Amidoximes: Synthesis of Oxadiazoles. Heterocycles. 2001, 52(2), 985-988.

SANGSHETTI, J.N., NAGAWADE, R.R. and SHINDE, D.B. Synthesis of novel 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-5(4H)-one as antifungal agents. Bioorganic & Medicinal Chemistry Letters. 2009, 19(13), 3564-3567.

SANTOS, C.E.M. Toxicologia in silico: uma nova abordagem para análise do risco químico. Revista Intertox de Toxicologia, Risco Ambiental e Sociedade. 2011, 4(1), 47-63.

SANTOS, C.E.M. and RODRIGUES, A.S. Toxicologia in silico: contexto de aplicação e o modelo de custo-efetividade nos testes alternativos. RevInter Revista Intertox de Toxicologia, Risco Ambiental e Sociedade. 2011, 4(3), 92-113.

SARVI, I., GHOLIZADEH, M. and IZADYAR, M. Threonine stabilizer-controlled well-dispersed small palladium nanoparticles on modified magnetic nanocatalyst for Heck cross-coupling process in water. Applied Organometallic Chemistry. 2018, 33(3), 1-10.

SAUER, A.C., et al. A Straightforward and High-Yielding Synthesis of 1,2,4-Oxadiazoles from Chiral N-Protected α-Amino Acids and Amidoximes in Acetone-Water: An Eco-Friendly Approach. Journal of Chemistry. 2019, 2019, 1-9.

SIDRIM, J.J.C. and ROCHA, M.F.G. Micologia Médica à luz de autores contemporâneos. 2nd ed. Rio de Janeiro: Guanabara Koogan, 2010.

SILVA, A.S., SILVA, J.M., ALMEIDA, A.V. and RAMOS, C.S. Herbivory Causes Chemical and Biological Changes on Essential Oil from Piper marginatum Leaves. The Natural Products Journal. 2016, 6(4), 313-317.

SILVA, D.F. Avaliação da atividade biológica do β-citroneol sobre Candida albicans. João pessoa: Universidade Federal da Paraíba, 2016. Dissertação de mestrado.

SINGH, P., et al. Synthesis and evaluation of substituted diphenyl-1,3,4-oxadiazole derivatives for central nervous system depressant activity. Bioorganic & Medicinal Chemistry Letters. 2012, 2(1), 1-8.

SRINIVAS, N., SANDEEP, K.S., ANUSHA, Y. and DEVENDRA, B.N. In vitro cytotoxic evaluation and detoxification of monocrotaline (Mct) alkaloid: an in-silico approach. International Invention Journal Biochemistry Bioinformatics. 2014. 2(2), 20-29.

TALE, R.H., et al. Synthesis and anti-bacterial, anti-fungal activity of novel 1,2,4-oxadiazole. Journal of Chemical and Pharmaceutical Research. 2011, 3(2), 496-505.

TERRÍVEL, J., et al. Conhecimento dos médicos relativo à prescrição de antibióticos e à resistência microbiana: estudo piloto de comparação de questionário online vs papel. Revista de Epidemiologia e Controle de Infecção. 2013, 3(3), 93-98.

VARANO, N., et al. Infecções por Candida spp em pacientes imunodeprimidos. Journal of Infection Control. 2019, 8(1), 17-23.

WALSH, C. Antibiotics: actions, origins, resistance. Protein Science. 2004, 13(11), 3059-3060.

ZAKERI, M., HERAVI, M.M. and ABOUZARI-LOTF, E. A new one-pot synthesis of 1,2,4-oxadiazoles from aryl nitriles, hydroxylamine and crotonoyl chloride. Journal of Chemical Sciences. 2013, 125(4), 731-735.

ZORZI, R.R. Planejamento, síntese e avaliação da atividade antimicrobiana de furfurilidênicos frente a micro-organismos causadores de infecções hospitalares. São Paulo: Universidade de São Paulo, 2013. Dissertação de mestrado.




How to Cite

LIMA, J.A. da C., COSTA, E.C.S., BEZERRA, G.B., SILVA, J. de F., ALVES CAIANA, R.R., DE FREITAS FILHO, J.R. and FREITAS, J.C.R., 2022. Synthesis, antimicrobial evaluation and in silico studies of the (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles. Bioscience Journal [online], vol. 38, pp. e38005. [Accessed21 July 2024]. DOI 10.14393/BJ-v38n0a2022-54382. Available from:



Health Sciences