EVALUATION OF BACTERICIDAL AND FUNGICIDAL ACTIVITY OF SULFUR-CONTAINING 2,3-DIHYDROIMIDAZO[2,1-b]THIAZOLES
DOI:
https://doi.org/10.32782/pcsd-2022-4-10Keywords:
functionalized imidazo[2,1-b]thiazoles, bioscreening, bactericidal activity, fungicidal activityAbstract
Imidazo[2,1-b]thiazoles belong to privileged heterocyclic systems and use the increased attention of researchers, due to their powerful medical and biological potential. In order to find non-toxic antimicrobial agents, it was advisable to study the bactericidal and fungicidal activity of sulfunctionalized imidazo[2,1-b]thiazoles. Model objects, S-(tetrahydroimidazo[2,1-b]thiazolylmethyl)thioacetates 2a,b, O-butyl S-(tetrahydroimidazo[2,1-b]thiazolylmethyl) carbonodithioates 3a-d and 6-(propan-2-ylidene)-2-thiocyanatomethylimidazo[2,1-b]thiazolone 4, were synthesized by the reaction of nucleophilic substitution bromine and iodine atoms in 2-halogenomethyl-2,3-dihydroimidazo[2,1-b] thiazolones on thioacetate, butylxantogenate and thiocyanate functions. The results of bioscreening showed that the investigated compounds are characterized by moderate bactericidal and fungicidal activity, which were estimated by the quantities of inhibition of test cultures, as well as by the quantities of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (МВС) by the serial dilutions technique. It is established that the best antimicrobial and antifungal effect is 6-(propan-2-ylidene)thiocetate 2b, which at a concentration of 0.5% inhibits the growth of bacteria Micrococcus luteus in diameter 12 mm and fungus Аspergillus niger in diameter 13 mm. In determining the minimum bacteriostatic concentration (MBC) and the minimum fungistatic concentration (MFC) of the compounds 2-4 by the method of serial dilutions technique it was established that they have antimicrobial action at concentrations of 15.6-500 μg/ml. Found that O-butyl S-(6-benzylydenetetrahydroimidazo[2,1-b]thiazolylmethyl)carbonodithioate 3d at a concentration of 31.2 μg/ml shows an inhibitory active against micrococcus luteus, and 6-(propan-2-ylidene)-2- thiocyanatomethylimidazo[2,1-b]thiazolone 4 – against Candida tenuis at a concentration of 15.6 μg/ml.
References
Hecht, D. W. Prevalence of Antibiotic Resistance in Anaerobic Bacteria: Worrisome Developments. Clin. Infect. Dis. 2004. 39(1). P. 92-97.
Kamal, A., Kashi Reddy, M., Viswanath, A. The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs. Expert Opin. Drug Discov. 2013. 8(3). P. 289-304.
Fascio, M.L., Errea, M.I., D'Accorso, N.B. Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological properties. Eur. J. Med. Chem. 2015. 90. P. 666-683.
Tojo, S., Kohno, T., Tanaka, T., Kamioka, S., Ota, Y., Ishii, T., Kamimoto, K., Asano, S., Isobe Y. Crystal Structures and Structure-Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors. ACS Med. Chem. Lett. 2014. 5(10). P. 1119-1123.
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. Comp. 2020. 56(11). P. 1394-1407.
Amarouchi, H., Loiseau, P. R., Bacha, C., Caujolle, R., Payard, M., Loiseau, P. M., Bories, C., Gayral, P. Imidazo[2,1-b]thiazoles: analogues du levamisole. Eur. J. Med. Chem. 1987. 22. P. 463-466.
Liu, K. G., Robichaud, A. J., Bernotas, R. C., Yan, Y., Lo, J. R., Zhang, M.-Y., Hughes, Z. A., Huselton, C., Zhang, G. M., Zhang, J. Y., Kowal, D. M., Smith, D. L., Schechter, L. E., Comery, T. A. 5-Piperazinyl-3-sulfonylindazoles as Potent and Selective 5-Hydroxytryptamine-6 Antagonists. J. Med. Chem. 2010. 53. P. 7639-7646.
Da Pozzo, E., La Pietra, V., Cosimelli, B., Da Settimo, F., Giacomelli, C., Marinelli, L., Martini, C., Novellino, E., Taliani, S., Greco, G. p53 Functional Inhibitors Behaving Like Pifithrin-β Counteract the Alzheimer Peptide Non-β-amyloid Component Effects in Human SHSY5Y Cells. ACS Chem. Neurosci. 2014. 5. P. 390-399.
Салієва Л. М., Васькевич Р. І., Сливка Н. Ю., Вовк М. В. Синтез і структурна функціоналізація 6-заміщених 2,3-дигідроімідазо[2,1-b][1,3]тіазол-5-онів. Журн. орг. фарм. хім. 2018. 16(2). C. 31-41.
NCCLS, Performance Standards for Antimicrobial Disk Susceptibility Tests – Fourth Edition: Approved Standards, Document M2-A4, NCCL S, Villanova, PA, 1990.
NCCLS, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Conidium Forming Filamentous Fungi: Proposed Standard, Document M38-P, NCCL S, Wayne, PA, 1998.
