Synthesis, the antiexudative and antimicrobial activity of 6-arylidene substituted imidazo[2,1-b]thiazoles

Authors

DOI:

https://doi.org/10.24959/ophcj.21.227378

Keywords:

2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone; arylaldehydes; Knoevenagel condensation; 6-arylidene-2-methyl-2,3-dihydroimidazo[2,1-b]thiazolones; antiexudative activity; antimicrobial activity

Abstract

Aim. To expand the range of 6-arylidene-2-methyl-2,3-dihydroimidazo[2,1-b]thiazolones as potential objects for studying the antiexudative and antimicrobial activities.

Results and discussion. It has been shown that the condensation of synthetically affordable 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with aromatic aldehydes can be successfully used for obtaining the corresponding 6-ylidene-functionalized derivatives. The biological screening of the compounds synthesized revealed that they possessed a low or moderate anti-inflammatory activity and inhibited the inflammation process in the range from 3 to 44 %. During the study of the antimicrobial activity of the substances obtained it was determined that their minimum bacteriostatic and minimum fungistatic concentrations ranged from 31.25 to 250 μg/mL.

Experimental part. The interaction of 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with a series of benzaldehydes and salicylic aldehydes in refluxing acetic acid in the presence of anhydrous sodium acetate leads to new 6-arylidene-2-methyl-2,3-dihydroimidazo[2,1-b]thiazolones. The antiexudative activity screening was performed on the model of carrageenan-induced paw oedema of white outbred male rats. The antimicrobial activity of the compounds was studied using the microtechnique of two-fold serial dilutions in a liquid nutrient medium.

Conclusions. It has been found that the Knoevenagel condensation of 2-methyl-2,3-dihydroimidazo[2,1-b]thiazolone with aromatic aldehydes is a convenient way for the structural modification of the position 6 of the heterocyclic system by the arylidene moiety. The arylidene derivatives obtained show a moderate antiexudative activity in the carrageenan-induced rat paw oedema assay, as well as the antimicrobial activity against some gram-positive and gram-negative bacteria and fungi.

References

Saliyeva, L. N.; Diachenko, I. V.; Vas’kevich, R. I.; Slyvka, N. Yu.; Vovk, M. V. Imidazothiazoles and their hydrogenated analogs: methods of synthesis and biomedical potential. Chem. Heterocycl. Compd. 2020, 56 (11), 1394 – 1407. https://doi.org/10.1007/s10593-020-02827-w.

Tikhonova, T. A.; Rassokhina, I. V.; Kondrakhin, E.A.; Fedosov, M. A.; Bukanova, J. V.; Rossokhin, A. V.; Sharonova, I. N.; Kovalev, G. I.; Zavarzin, I. V.; Volkova, Yu. A. Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABAA receptors. Bioorg. Chem. 2020, 94, 103334. https://doi.org/10.1016/j.bioorg.2019.103334.

Cole, D. C.; Stock, J. R.; Lennox, W. J.; Bernotas, R. C.; Ellingboe, J. W.; Boikess, S.; Coupet, J.; Smith, D. L.; Leung, L.; Zhang, G.-M.; Feng, X.; Kelly, M. F.; Galante, R.; Huang, P.; Dawson, L. A.; Marquis, K.; Rosenzweig-Lipson, S.; Beyer, C. E.; Schechter, L. E. Discovery of N1-(6-Chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a Potent, Selective, and Orally Active 5-HT6 Receptor Agonist. J. Med. Chem. 2007, 50 (23), 5535 – 5538. https://doi.org/10.1021/jm070521y.

Bemis, J.; Disch, J. S.; Jirousek, M.; Lunsmann, W. J.; Ng, P. Y.; Vu, C. B. Sirtuin Modulating Imidazothiazole Compounds. International Patent WO2008156866A1, Dec 24, 2008.

Bekaddour, B. N.; Rodero, M.; Herbeu-Val, J.-P.; Pietrancosta, N.; Smith, N. Imidazoline Derivatives as CXCR4 Modulators. International Patent WO2020201096A1, Oct 8, 2020.

Koudad, M.; Hamouti, C. E.; Elaatiaoui, A.; Dadou, S.; Oussaid, A.; Abrigach, F.; Pilet, G.; Benchat, N.; Allali, M. Synthesis, crystal structure, antimicrobial activity and docking studies of new imidazothiazole derivatives. J. Iran. Chem. Soc. 2020, 17, 297 – 306. https://doi.org/10.1007/s13738-019-01766-4.

Shareef, M. A.; Sirisha, K.; Sayeed, I. B.; Khan, I.; Ganapathi, T.; Akbar, S.; Kumar, C. G.; Kamal, A.; Nagendra Babu, B. Synthesis of new triazole fused imidazo[2,1-b]thiazole hybrids with emphasis on Staphylococcus aureus virulence factors. Bioorg. Med. Chem. Lett. 2019, 29 (19), 126621. https://doi.org/10.1016/j.bmcl.2019.08.025.

Leoni, A.; Frosini, M.; Locatelli, A.; Micucci, M.; Carotenuto, C.; Durante, M.; Cosconati, S.; Budriesi, R. 4-Imidazo[2,1-b]thiazole-1,4-DHPs and neuroprotection: preliminary study in hits searching. Eur. J. Med. Chem. 2019, 169, 89 – 102. https://doi.org/10.1016/j.ejmech.2019.02.075.

Baig, M. F.; Nayak, V. L.; Budaganaboyina, P.; Mullagiri, K.; Sunkari, S.; Gour, J.; Kamal, A. Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents. Bioorg. Chem. 2018, 77, 515 – 526. https://doi.org/10.1016/j.bioorg.2018.02.005.

Nagireddy, P. K. R.; Kommalapati, V. K.; Krishna, V. S.; Sriram, D.; Tangutur, A. D.; Kantevari, S. Imidazo[2,1-b]thiazole-Coupled Natural Noscapine Derivatives was Anticancer Agents. ACS Omega 2019, 21 (4), 19382 – 19398. https://doi.org/10.1021/acsomega.9b02789.

Noha, R. M.; Abdelhameid, M. K.; Ismail, M. M.; Manal, R. M.; Salwa, E. Design, Synthesis and Screening of Benzimidazole Containing Compounds with Methoxylated Aryl Radicals as Cytotoxic Molecules on (HCT-116) Colon Cancer Cells. Eur. J. Med. Chem. 2020, 209, 112870. https://doi.org/10.1016/j.ejmech.2020.112870.

Zhang, Q.; Zhao, K.; Zhang, L.; Jiao, X.; Zhang, Y.; Tang, C. Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Bioorg. Med. Chem. Lett. 2020, 30 (23), 127525. https://doi.org/10.1016/j.bmcl.2020.127525.

Diana, S.; Moghimi, S.; Mahdavi, M.; Nadri, H.; Moradi, A.; Firoozpour, L.; Emami, S.; Mouradzadegun, A.; Shafiee, A.; Foroumadi, A. Quinoline-based imidazole-fused heterocycles as new inhibitors of 15-lipoxygenase. J. Enzyme Inhib. Med. Chem. 2016, 31 (sup3), 205 – 209. https://doi.org/10.1080/14756366.2016.1206087.

Serafini, M.; Torre, E.; Aprile, S.; Massarotti, A.; Fallarini, S.; Pirali, T. Synthesis, Docking and Biological Evaluation of a Novel Class of Imidazothiazoles as IDO1 Inhibitors. Molecules 2019, 24 (10), 1874. https://doi.org/10.3390/molecules24101874.

Amarouch, H.; Loiseau, P. R.; Bacha, C.; Caujolle, R.; Payard, M.; Loiseau, P. M.; Bories, C.; Gayral, P. Imidazo[2,1-b]thiazoles: analogues of levamisole. Eur. J. Med. Chem. 1987, 22 (5), 463 – 466. https://doi.org/10.1016/0223-5234(87)90037-7.

Saliyeva, L. M.; Slyvka, N. Yu.; Vas’kevych, R. I.; Vovk, M. V. Synthesis of 2,3-dihydroimidazo[2,1-b][1,3]thiazole derivatives by electrophilic cyclization of 3-allyl-2-thioxoimidazolidin-4-ones. Ukrainian Chemistry Journal 2016, 82 (5), 64 – 70.

Saliyeva, L. N.; Slyvka, N. Yu.; Mel’nyk, D. A.; Rusanov, E. B.; Vas’kevich, R. I.; Vovk, M. V. Synthesis of spiro[imidazo[2,1-b][1,3]thiazole-6,3’-pyrrolidine]derivatives. Chem. Heterocycl. Compd. 2018, 54 (2), 130 – 137. https://doi.org/10.1007/s10593-018-2244-8.

Ye, X.; Zhou, W.; Li, Y.; Sun, Y.; Zhang, Y.; Ji, H.; Lai, Y. Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo. Cancer Chemother Pharmacol. 2010, 66, 277 – 285. https://doi.org/10.1007/s00280-009-1161-z.

Kouzi, O.; Pontiki, E.; Hadjipavlou-Litina, D. 2-Arylidene-1-indandiones as Pleiotropic Agents with Antioxidant and Inhibitory Enzymes Activities. Molecules 2019, 24 (23), 4411. https://doi.org/10.3390/molecules24234411.

Jain, S.; Kumar, A.; Saini, D. Novel arylidene derivatives of quinoline based thiazolidinones: Synthesis, in vitro, in vivo and in silico study as antimalarials. Exp. Parasitol. 2018, 185, 107 – 114. https://doi.org/10.1016/j.exppara.2018.01.015.

Rajagopalan, P.; Dera, A.; Abdalsamad, M. R.; Chandramoorthy, H. C. Rational combinations of indirubin and arylidene derivatives exhibit synergism in human non-small cell lung carcinoma cells. J. Food Biochem. 2019, 43 (7), 12861. https://doi.org/10.1111/jfbc.12861.

Khodair, A. I.; Gesson, J.-P. Sulfur glycosylation reactions involving 3-allyl-2-thiohydantoin nucleoside bases as potential antiviral and antitumor agents. Phosphorus, Sulfur Silicon Relat. Elem. 1998, 142 (1), 167 – 190. https://doi.org/10.1080/10426509808029674.

Desai, N. C.; Vaghani, H. V.; Rajpara, K. M.; Joshi, V. V.; Satodiya, H. M. Novel approach for synthesis of potent antimicrobial hybrid molecules containing pyrimidine-based imidazole scaffolds. Med. Chem. Res. 2014, 23 (10), 4395 – 4403. https://doi.org/10.1007/s00044-014-1005-1.

Winter, C. A.; Risley, E. A.; Nuss, G. W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc. Soc. Exp. Biol. Med. 1962, 111 (3), 544 – 547. https://doi.org/10.3181/00379727-111-27849.

Yakovychuk, N. D.; Deyneka, S. Y.; Grozav, A. M.; Humenna, A. V.; Popovych, V. B.; Djuiriak, V. S. Аntifungal activity of 5-(2-nitrovinyl)imidazoles and their derivatives against the causative agents of vulvovaginal candidiasis. Regulatory Mechanisms in Biosystems 2018, 9 (3), 369 – 373. https://doi.org/https://doi.org/10.15421/021854.

Про затвердження методичних вказівок «Визначення чутливості мікроорганізмів до антибактеріальних препаратів». https://zakon.rada.gov.ua/rada/show/v0167282-07#Text (accessed May 15, 2021), Міністерство охорони здоров’я України, Наказ №167 від 05.04.2007.

Published

2021-06-23

Issue

Section

Articles