Síntese e avaliação in silico do potencial farmacológico de 1,2,4-oxadiazol 3,5-dissubstituído

Dayseane Sales Bernardo Campelo; João Rufino de Freitas Filho; Clécio Souza Ramos; José Rufino de Freitas; Queila Patrícia Barbosa da Silva Freitas; Juliano Carlo Rufino de Freitas

doi:10.22481/exon.v14i2.20557

Authors

Dayseane Sales Bernardo Campelo Universidade Federal Rural de Pernambuco
João Rufino de Freitas Filho Universidade Federal Rural de Pernambuco
Clécio Souza Ramos Universidade Federal Rural de Pernambuco
José Rufino de Freitas Universidade Federal Rural de Pernambuco
Queila Patrícia Barbosa da Silva Freitas Universidade Federal Rural de Pernambuco
Juliano Carlo Rufino de Freitas Universidade Federal Rural de Pernambuco

DOI:

https://doi.org/10.22481/exon.v14i2.20557

Keywords:

Amidoxime, 1,2,4-oxadiazole, in silico study, pharmacological

Abstract

Oxadiazoles heterocycles are presente in many structures with different pharmacological properties. However, the five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. The literature reports a growing number of publications involving 1,2,4- oxadiazoles over recent years, which have been focused on its different pharmacological potentials. In this work, the synthesis, structural characterization and in silico evaluation of 1,2,4-oxadiazoles is described. (Z)-4-(fluoromethyl) benzamidoxime (3a) and (Z)-3-(trifluoromethoxy) benzamidoxime, starting products of interest, were

obtained in good yields (85% 3a e 93% 3b). On the other hand, 2-(3-aryl-1,2,4-oxadiazol-5-yl)-3,4- (methylenedioxy)-cinnamyl (6a-b) were obtained from methyl trans-3,4-(methylenedioxy)-cinnamate and arylamidoxime by irradiation in a focused microwave oven yields 88 and 65%, respectively. Additionally, the in silico study indicated that all synthesized compounds have a low risk of chronic toxicity and can be administered orally. In addition, there are strong physicochemical indications that support the likelihood of these compounds presenting anxiolytic, antidiabetic, antiemetic, and antiprotozoal activity.

Downloads

Download data is not yet available.

References

J. M. Dhameliya, S.J. Chudasma, T. M. Patel, B. P. Dave. A review on synthetic account of 1,2,4- oxadiazoles as anti-infective agentes. Mol Divers, p. 1-14, 2022.

V. J. Ram, A. Seth Nath M, R. Pratap. Chapter 5 – Five- Membered Heterocycles. The Chemistry of Heterocycles. Elsevier, 2019.

P. S. Thacker, A. Angelim, O. S. Argulwar, P. L. Tiwari, M. Arifuddin, C. T. Supuran. (2020). Design, synthesis and biological evaluation of coumarin linked 1,2,4-oxadiazoles as selective carbonic anhydrase IX and XII inhibitors. Bioorganic Chemistry, 98, 103739, 2020.

da Silva, A. R. F, Moura A. L, Souza F. A. M, Bezerra G. B, Freitas J. J. R, de Freitas Filho J. R. Synthesis and antimicrobial activity of 3-[3,4,5-trimethoxyphenyl]-[1,2,4- oxadiazol-5-yl] propanone. Braz. J. of Develop., v. 6, n.12, p. 94401-94414, 2020.

M. Arshad, T. A. Khan, M. A. Khan. 1,2,4-oxadiazole nucleus with versatile biological applications. International Journal of Pharma Sciences and Research, v. 5, n. 7, p. 91–110, 2014.

F. S. Cunha, A. P. de Aguiar, A. P. Síntese e Bioatividade de 1 , 2 , 4-Oxadiazóis. Revista Virtual de Química, v. 7, n. 6, p. 2509-2530, 2015.

Y. Y. Zhang, Q. Q. Zhang, J. Zhang, J. L. Song, J. C. Li, K. Han, J. T. Huang, C. S. Jiang, H. Zhang. Synthesis and evaluation of 1,2,4-oxadiazole derivatives as potential antiinflammatory agents by inhibiting NF-κB signaling pathway in LPSstimulated RAW 264.7 cells. Bioorganic Chemistry, v. 30, n. 17, p. 127373, 2020.

A. E. El Mansouri, A. Oubella, M. Maatallah, M. Y. AitItto, M. Zahouily, H. Morjani, H. B. Lazrek. Design, synthesis, biological evaluation and molecular docking of new uracil analogs-1,2,4-oxadiazole hybrids as potential anticancer agents. Bioorg Med Chem Lett. V. 30, n. 19, p.127438, 2020.

J. J. R. Freitas, E. E. Silva, J. L. L. F. Regueira, S. A. De Andrade, P. M. M. Cavalcante, R. N. Oliveira, J. R. Freitas Filho (2012). 1,2,4-Oxadiazoles: Synthesis and applications. Revista Virtual de Quimica, v. 4, n. 6, p. 670–691, 2012.

A. P. Piccionello, I. Pibiri, A. Pace, P. Pierro, S. Buscemi, N. Vivona. On the reaction of some 5- polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine: synthesis of fluorinated indazoles. Tetrahedron, v. 65, p. 119-127, 2009.

S. V. Baikov, G. A. Stashina, E. I. Chernoburova, V. B. Krylov, L. V. Zavarzin, E. R. Kofanov. The reaction of amidoximes with carboxylic acids or their esters under high-pressure conditions. Russian Chemical Bulletin, v. 68, n. 2, p. 347–350, 2019.

S. Baykov, T. Sharonova, A. Shetnev, S. Rozhkov, S. Kalinin, A. V. Smirnov. (2017) The first one pot ambient-temperature synthesis of 1,2,4-oxadiazoles from amidoximes and carboxylic acid esters. Tetrahedron, v. 73, n. 7, p. 945–951, 2017.

K. Biernacki, M. Dasko, O. Ciupak, K. Kubinski, J. Rachon, S. Demkowicz. Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery. Pharmaceuticals, v. 13, n. 6, p. 111, 2020.

M. Adib, A. H. Jahromi, N. Tavoosi, M. Mahdavia, H. R. Bijanzadeh. Microwave-assisted efficient, one-pot, three-component synthesis of 3,5-disubstituted 1,2,4-oxadiazoles under solvent-free conditions. Tetrahedron Lett. v. 47, n. 17, p. 2965- 2967, 2006.

M. Ouattara, S. Wein, S. Denoyelle, S. Ortial, T. Durand, R. Escale, H. Vial, Y. Vo-Hoang. Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents. Bioorg. Med. Chem. Lett. v. 19, n. 3, p. 624-626, 2009.

D. Kumar, G. Patel, E. O. Johnson, K. Shah. Synthesis and anticancer activities of novel 3,5- disubstituted-1,2,4-oxadiazoles. Bioorg. Med. Chem. Lett. v. 19, n. 10, p. 2739-2741, 2009.

K. Otaka, J. Ikeda, D. Tanaka, M. Tobe. Construction of 3,5-substituted 1,2,4-oxadiazole rings triggered by tetrabutylammonium hydroxide: a highly efficient and fluoride-free ring closure reaction of O-acylamidoximes.Tetrahedron Letters. v. 55, n. 5, p. 979-981, 2014.

M. Carbone, Y. Li, C. Irace, E. Mollo, F. Castelluccio, A. D. Pascale, G. Cimino, R. Santamaria, Y. G. Guo, M. Gavagnin, M. Structure and Cytotoxicity of Phidianidines A and B: First Finding of 1,2,4- Oxadiazole System in a Marine Natural Product. Organic Letters, v. 13, n. 10, p. 2516–2519, 2011.

D. Andrade, J. R. Freitas Filho, J. C. R. Freitas. Aplicação de amidoximas como catalisadores da reação de alilação por aliltrifluoroborato de potássio em meio bifásico. Química Nova, v. 39, n. 10, p. 1225–1235, 2016.

C. J. P. Barros, J. J. R.. Freitas, R. N. Oliveira, J. R. F. Filho. A 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. v. 59, n. (1), p. 2359-2362, 2014.

J. A. C. Lima, E. C. S.Costa, G. B. Bezerra, J. F. Silva, R. A. Rodrigo Caina, J. R. de Freitas Filho, J. C. R. Freitas. (2020) Synthesis, antimicrobial activity, and in silico studies of 1,2,4-oxadiazoles from ethyl levulinate. Acta Brasiliensis, v. 4, n. 3, p. 161-167, 2020.

A. S. Voisin-Chiret, M. A. Bazin, J. C. Lancelot, S. Rault. (2007). Synthesis of new L-ascorbic ferulic acid hybrids. Molecules (Basel, Switzerland), v. 12, n. 11, p. 2533–2545, 2007.

C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. v. 46, n. 1-3, p. 3-26, 2001.

C. A. Lipinski. Lead and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol., v. 1, n. 4, p. 337-341, 2004.

A. Daina, O. Michielin, V. Zoete. Swiss ADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Sci. Rep., v. 7, n. 1, p. 1-13, 2017.

A. O. Maslat, M. Abussaud, H. Tashtoush, M. AL-Talib. Synthesis, antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives. Pol. J. Pharmacol., v. 54, n. 1, p. 55-59, 2002.

T. S. Ibrahimab, A. J. Almalkia, A. H. Moustafac, R. M. Allamd, G. E. D. A. Abuo-Rahmaef, H. I. E. Subbaghg, M. F. A. Mohamedh. Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study. Bioorg. Chem., v. 111, p. 104885, 2021.