Synthesis, characterization, and antimicrobial evaluation of novel 1,2,4-oxadiazoles derived from trans-3,4-(methylenedioxy)-cinnamic acid

Abstract

Compounds containing heterocyclic ring systems are of great importance both medicinally and industrially. Five-membered 1,2,4-oxadiazole heterocycles have received considerable attention because of their unique bioisosteric properties and unusual wide spectrum of biological activities. In this study, a series of 2-(3-aryl-1,2,4-oxadiazol-5-yl)-trans-3,4-(methylenedioxy)-cinnamyl derivatives was synthesized and characterized, and in vitro experimental models were used to evaluate their antimicrobial activity. Synthesis, which involved microwave irradiation for 5 min, provided moderate yields of 1,2,4-oxadiazole (34–50%). Infrared (IR) and nuclear magnetic resonance (1H NMR  and 13C NMR) spectroscopy were used to determine the structures of 1,2,4-oxadiazole. The disk diffusion method was used to test the antibacterial activity of the novel 1,2,4-oxadiazole derivatives against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. The derivatives, 2-(3-m-toluyl-1,2,4-oxadiazol-5-yl)-3,4-(methylenedioxy)-cinnamyl and 2-(3-pyrimidyl-1,2,4-oxadiazol-5-yl)-3,4-(methylenedioxy)-cinnamyl exhibited a minimum inhibitory concentration (MIC) of 19.5 μg mL−1 against S. aureus, and is four-fold more potent than the standard metronidazole (MIC =78 μg mL−1).

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Author Biographies

João Rufino de Freitas Filho, Programa de Pós-Graduação em Química, Universidade Federal Rural de Pernambuco, Dois Irmão, Recife, Pernambuco, Brazil

Doutor em Química Orgânica e atualmente professor do Programa de Pós-Graduação em Química da Universidade Federal rural de Pernambuco.

Clécio Souza Ramos, Programa de Pós-Graduação em Química, Universidade Federal Rural de Pernambuco, Dois Irmão, Recife, Pernambuco, Brazil

Doutor em Química e Professor da pós-graduação em química do Departamento de Química da Universidade Federal Rural de Pernambuco.

Leonardo Alexandre Barros Bezerra, Programa de Pós-Graduação em Química, Universidade Federal Rural de Pernambuco, Dois Irmão, Recife, Pernambuco, Brazil

Estudante do doutorado do programa de Pós-Graduação em Química do Departamento de Química da Universidade Federal Rural de Pernambuco.

Marcílio Wagner Fonte Silva, Programa de Pós-Graduação em Química, Universidade Federal Rural de Pernambuco, Dois Irmão, Recife, Pernambuco, Brazil

Estudante do doutorado em Química do Programa de Pós-Graduação em Química do Departamento de Química da Universidade Federal Rural de Pernambuco.

Giselle Barbosa Bezerra, Autarquia de Ensino Superior de Arcoverde, São Cristóvão, Arcoverde, 56512-200, Pernambuco, Brazil

Doutora em química pelo Programa de Pós-Graduação em Química do departamento de Química da Universidade Federal Rural de Pernambuco.

Jucleiton José Rufino de Freitas, Universidade Federal Rural de Pernambuco, Cabo de Santo Agostinho, Pernambuco, Brazil

Doutor em Química e Professor de química orgânica da Unidade Acadêmica do cabo de santo Agostinho da Universidade Federal Rural de Pernambuco.

Queila Patrícia da Silva Barbosa Freitas, Colégio de Aplicação, Universidade Federal Rural de Pernambuco, Recife, Pernambuco, Brazil

Doutora em Química e Professora do Colégio de Aplicação da Universidade Federal de Pernambuco.

References

Aliabadi A. (2016). 1,3,4-Thiadiazole based anticancer agents. Anti-cancer agentes in medicinal chemistry, 16(10), 1301-1314. doi: /10.2174/1871520616666160628100936
Andrade, D., Freitas Filho, J. R., & Freitas, J. C. R. (2016). Aplicação de amidoximas como catalisadores da reação de alilação por aliltrifluoroborato de potássio em meio bifásico. Química Nova, 39(10), 1225-1235. http://dx.doi.org/10.21577/0100-4042.20160158
Baral, N., Mohapatra, S., Raiguru, B. P., Mishra, N. P., Panda, P., Nayak, S., Pandey, S. K., Kumar, P. S., &Sahoo, C. R.J. (2019). Microwave-Assisted Rapid and Efficient Synthesis of New Series of Chromene-Based 1,2,4-Oxadiazole Derivatives and Evaluation of Antibacterial Activity with Molecular Docking Investigation. Heterocyclic Chem, 56, 552-565. https://doi.org/10.1002/jhet.3773
Bezerra, N. M. M., De Oliveira, S. P., Srivastava, R. M., &da Silva, J. R. (2005). An easy synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and arylamidoximes mediated by ethyl chloroformate. II Farmaco, 60, 955. http://dx.doi.org/10.1016/j.farmac.2005.08.003
Biernacki, K., Dásko, M., Ciupak, O., Kubinsk, K. Rachon, J., Demkowicz, S. (2020). Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery. Pharmaceuticals, 13(6), 1-45. https://doi.org/10.3390/ph13060111
Bora, R. O., Dar, B., Pradhan, V., & Farooqui, M. (2014). 1, 2, 4-oxadiazoles: synthesis and biological applications. Mini-reviews in Medicinal Chemistry, 14(4), 355-369. doi: 10.2174 / 1389557514666140329200745
Brotschi, C., Roch, C., Gatfield, J., Treiber, A., Williams, J. T., Sifferlen, T., Heidmann, B., Jenck, F., Bolli, M. H., &Boss, C. (2019). Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis, Structure-Activity Relationships, and Sleep-Promoting Properties in Rats. ChemMedChem, 14, 1257-1270, doi:10.1002/cmdc.201900242.
Chernyshov, V. V., Yarovaya, O. I., Esaulkova, I. L., Sinegubova, E. Borisevich, S. S., Popadyuk, I. I., Zarubaev, V. V., &Salakhutdinov, N. F. (2022). Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses. Bioorganic & Medicinal Chemistry Letters, 1(55), 128465. doi: 10.1016/j.bmcl.2021.128465. Epub 2021 Nov 19. PMID: 34808389
Clinical and Laboratory Standards Institute. (2010). Performance standards for antimicrobial susceptibility testing, Document M100-S20, 2010. Wayne, PA.
De Vita, D., Friggeri, L., D'Auria, F. D., Pandolfi, F., Piccoli, F., Panella, S., Palamara, A. T., Simonetti, G., Scipione, L., Di Santo, R., Costi, R., & Tortorella, S. (2014). Activity of caffeic acid derivatives against Candida albicans biofilm. Bioorganic & medicinal chemistry letters, 24(6), 1502-1505. https://doi.org/10.1016/j.bmcl.2014.02.005
Debnath, B., Samanta, S., Roy, K., & Jha, T. (2003). QSAR study on some p-arylthio cinnamides as antagonists of biochemical ICAM-1/LFA-1 interaction and ICAM-1/JY-8 cell adhesion in relation to anti-inflammatory activity. Bioorganic & medicinal chemistry, 11(8), 1615-1619. https://doi.org/10.1016/s0968-0896(03)00085-3
Espinel-Ingroff, A., Fothergill, A., Ghannoum, M., Manavathu, E., Ostrosky-Zeichner, L., Pfaller, M., Rinaldi, M., Schell, W., & Walsh, T. (2005). 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, 43(10), 5243-5246. https://doi.org/10.1128/JCM.43.10.5243-5246.2005
Farooqui, M., Bora, R., &Patil, C. R. (2009). Synthesis, analgesic and anti-inflammatory activities of novel 3-(4-acetamido-benzyl)-5-substituted-1,2,4-oxadiazoles. European Journal of Medicinal Chemistry, 44(2), 794-799. doi: 10.1016/j.ejmech.2008.05.022
Gobec, M., Tomašič, T., Markovič, T., Mlinarič-Raščan, I., Dolenc, M. S., Jakopin, Ž. (2015). Antioxidant and anti-inflammatory properties of 1,2,4-oxadiazole analogs of resveratrol. Chemico-Biological Interactions, 240, 200-207. doi: 10.1016/j.cbi.2015.08.018
Haugwitz, R.D., Martinez, A. J., Venslavsky, J., Angel, R. G., Maurer, B. V., Jacobs, G. A., Narayanan, V. L., Cruthers, L. R., &Szanto, J. (1985). Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles. J Med Chem, 28(9), 1234-41. doi: 10.1021/jm00147a019
Ibrahim, T. S., Almalki, A. J., Moustafa, A. H., Allam R. M., Abuo-Rahma, G. E-D. A., El Subbagh, H. I., &Mohamed, M. F. A. (2011). Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study. Bioorganic Chemistry, 111, 104885. https://doi.org/10.1016/j.bioorg.2021.104885
Kumar, D., Patel, G., Chavers, A. K., Chang, K.-H., &Shah, K. (2011). Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents. European Journal of Medicinal Chemistry. 46(7), 3085-3092.http://dx.doi.org/10.1016/j.ejmech.2011.03.031
Lima, J. A. C., Costa, E. C.S., Bezerra, G. B., Silva, J. F., Rodrigo Caina, R. A., de Freitas Filho, J. R., & Freitas, J. C. R. (2020) Synthesis, antimicrobial activity, and in silico studies of 1,2,4-oxadiazoles from ethyl levulinate. Acta Brasiliensis, 4(3), 161-167. DOI: https://doi.org/10.22571/2526-4338390
Liu, Q., Zhu, R., Gao, S., Ma, S.-H., Tang, H.-J., Yang, J.-J., Diao, Y.-M., Wang, H.-L. and Zhu, H.-J. (2017), Structure-based bioisosterism design, synthesis, insecticidal activity and structure-activity relationship (SAR) of anthranilic diamide analogues containing 1,2,4-oxadiazole rings. Pest Management Science, 73, 917-924. https://doi.org/10.1002/ps.4363
Maftei, C. V., Fodor, E., Jones, P. G., Franz, M. H., Kelter, G., Fiebig, H., &Neda, I. (2013). Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties. Beilstein Journal of Organic Chemistry, 9, 2202-2215. https://doi.org/10.3762/bjoc.9.259.
Mohammadi-Khanaposhtani, M, Shabani, M., Faizi, M., &Aghaei, I. (2016). Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents. European Journal of Medicinal Chemistry, 112, 91-98. http://dx.doi.org/ 10.1016/j.ejmech.2016.01.054.
Moniot, S., Forgione, M., Lucidi, A., Hailu, G. S., Nebbioso, A., Carafa, V., Baratta, F., Altucci, L., Giacché, N., Passeri, D., Pellicciari, R., Mai, A., Steegborn, C., &Dante Rotili, D. (2017). Development of 1,2,4-oxadiazoles as potent and selective inhibitors of the human deacetylase sirtuin 2: structure-activity relationship, X-ray crystal structure, and anticancer activity, Journal of Medicinal Chemistry, 60(6), 2344-2360. http://dx.doi.org/10.1021/acs.jmedchem.6b01609.
Morales, G., Paredes, A., Sierra, P., &Loyola, L.A. (2008). Antimicrobial Activity of Three Baccharis Species Used in the Traditional Medicine of Northern Chile. Molecules, 13, 790-94. https://doi.org/10.3390/molecules13040790
Ölmez, N. A., & Waseer, F. (2020). New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivativpes Bearing 1,2,4-oxadiazole Ring. Current organic synthesis, 17(7), 525-534. https://doi.org/10.2174/1570179417666200417112106
Parrino, B., Carbone, D., Cascioferro, S., Pecoraro, C., Giovannetti, E., Deng, D., Di Sarno, V., Musella, S., Auriemma, G., Cusimano, M. G., Schillaci, D., Cirrincione, G., & Diana, P. (2021). 1,2,4-Oxadiazole topsentin analogs as staphylococcal biofilm inhibitors targeting the bacterial transpeptidase sortase A. European journal of medicinal chemistry, 209, 112892. https://doi.org/10.1016/j.ejmech.2020.112892
Puzanov, A. I., Ryabukhin, D. S., Zalivatskaya, A. S., Zakusilo, D. N., Mikson, D. S., Boyarskaya, I. A., &Vasilyev, A. V. (2021). Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions. Beilstein Journal of Organic Chemistry. 17, 2417-2424. https://doi.org/10.3762/bjoc.17.158
Rodrigues, M. P., Tomaz, D. C., Ângelo de Souza, L., Onofre, T. S., Aquiles de Menezes, W., Almeida-Silva, J., Suarez-Fontes, A. M., Rogéria de Almeida, M., Manoel da Silva, A., &Bressan, G. C., André Nanner-Santos, M., Lopes Rangel Fietto, J. & Ricardo Teixeira, R. (2019). Synthesis of Cinnamic Acid Derivatives and Leishmanicidal Activity against Leishmania Braziliensis. European Journal of Medicinal Chemistry, 183, 111688. https://doi.org/10.1016/j.ejmech.2019.111688
Ruwizhi, N., &Aderibigbe, B. A. (2020). Cinnamic Acid Derivatives and Their Biological Efficacy. International Journal of Molecular Sciences, 21, E5712. DOI: 10.3390/ijms21165712
Sova, M. (2012). Antioxidant and antimicrobial activities of cinnamic acid derivatives. Mini reviews in medicinal chemistry, 12(8), 749-767. https://doi.org/10.2174/138955712801264792
Sortino, M., Cechinel Filho, V., Corrêa, R., &Zacchino, S. (2008). N-Phenyl and N-phenylalkyl-maleimides acting against Candida spp.: Time-to-kill, stability, interaction with maleamic acids. Bioorganic & Medicinal Chemistry Letters, 16, 560-568. https://doi.org 10.1016/j.bmc.2007.08.030
Srivastava, R. M., Pereira, M. C., Faustino, W. W. M., Coutinho, K., Anjos, J. V., &Melo, S. J (2009). Synthesis, mechanism of formation, and molecular orbital calculations of arylamidoximes. Monatshefte fuer Chemie/Chemical Monthly, 140(11), 1319-1324. DOI:10.1007/s00706-009-0186-7
Vinaya, K., Chandrashekara, G. K.,&Shivaramu, P. D. (2019). One-pot synthesis of 3,5-diaryl substituted-1,2,4-oxadiazoles using gem-dibromomethylarenes. Canadian Journal of Chemistry, 97(9), 690-696. https://doi.org/10.1139/cjc-2018-0333
Voisin-Chiret, A. S., Bazin, M. A., Lancelot, J. C., & Rault, S. (2007). Synthesis of new L-ascorbic ferulic acid hybrids. Molecules (Basel, Switzerland), 12(11), 2533-2545. https://doi.org/10.3390/12112533
Yang, Sen, Chao-Li Ren, Tian-Yang Ma, Wen-Qian Zou, Li Dai, Xiao-Yu Tian, Xing-Hai Liu, &Cheng-Xia Tan. (2021). 1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo. International Journal of Molecular Sciences 22(5): 2367. https://doi.org/10.3390/ijms22052367
Yilmaz, S., Sova, M., &Ergün, S. (2018) Antimicrobial Activity of Trans-Cinnamic Acid and Commonly Used Antibiotics against Important Fish Pathogens and Nonpathogenic Isolates. Journal of Applied Microbiology, 125, 1714-1727. https://doi.org/10.1111/jam.14097
Zhang, B., Lv, C., Li, W., Cui, Z., Chen, D., Cao, F., Miao, F., & Zhou, L. (2015). Ethyl cinnamate derivatives as promising high-efficient acaricides against Psoroptes cuniculi: synthesis, bioactivity and structure-activity relationship. Chemical & pharmaceutical bulletin, 63(4), 255-262. https://doi.org/10.1248/cpb.c14-00765
Published
2022-01-31
How to Cite
DE FREITAS FILHO, João Rufino et al. Synthesis, characterization, and antimicrobial evaluation of novel 1,2,4-oxadiazoles derived from trans-3,4-(methylenedioxy)-cinnamic acid. Acta Brasiliensis, [S.l.], v. 6, n. 1, p. 6-13, jan. 2022. ISSN 2526-4338. Available at: <http://revistas.ufcg.edu.br/actabra/index.php/actabra/article/view/555>. Date accessed: 02 dec. 2024. doi: https://doi.org/10.22571/2526-4338555.