Substituted acyl thioureas and acyl thiosemicarbazides: synthesis and biological activity (minireview)
DOI:
https://doi.org/10.15587/2519-4852.2022.255738Keywords:
synthesis, acyl isothiocyanates, substituted anilines and aroyl hydrazides, nucleophilic addition, acyl thioureas, acyl thiosemicarbazides, complexes, biological activityAbstract
Acyl isothiocyanates and their functional derivatives (acyl thioureas and acyl thiosemicarbazides) are an important group of organic compounds that are widely used in the synthesis of heterocycles and in chemistry as catalysts, ligands, colorimetric hemosensors, etc. In recent years, there has been an increased interest towards this class of compounds as promising biologically active compounds, especially since the latest advances in medicinal chemistry for them are not sufficiently studied.
The aim. To summarize and systematize information for the last 10 years on methods of synthesis and biological activity of substituted acyl thioureas and acyl thiosemicarbazides.
Materials and methods. Web-tools for finding scientific information (Reaxys, Scopus, Google Scholar, ScienceResearch, SciFinder, Web of Science, etc.).
Results and discussion. Literature sources related to the methods of synthesis of substituted acyl thioureas and acyl thiosemicarbazides were systematized and analyzed. The main approaches for the formation of these compounds are revealed: stepwise formation from carboxylic acids, through acyl chlorides and acyl isothiocyanates followed by nucleophilic addition of amines or hydrazides of carboxylic acids ("one-pot synthesis"), nucleophilic addition of amines or hydrazides of carboxylic acids directly to acyl isothiocyanates and parallel microwave synthesis using acyl isothiocyanates and amines as reagents. The possibility of their use as ligands for the formation of complex compounds with transition metal ions was discussed. In the review biological activity of these structures, namely antimicrobial, fungicidal, antitumor, antiviral, antifungal and other activities was detailazed.
Conclusions. The basic approaches to the synthesis of substituted acylthuoureas and acyl thiosemicarbazides which include the application of carboxylic acids, their derivatives (acyl halides and isothiocyanates) and N-nucleophiles as initial compounds were discussed. It was shown that aforementioned class of the compounds reveals the versatile biological activity and are promising for further structural modification aimed to the search of novel drugs
References
- Bedane, K. G., Singh, G. S. (2015). Reactivity and diverse synthetic applications of acyl isothiocyanates. Arkivoc, 2015 (6), 206–245. doi: http://doi.org/10.3998/ark.5550190.p009.052
- Hemdan, M. M., Fahmy, A. F., Ali, N. F., Hegazi, E., Abd-Elhaleem, A. (2008). Synthesis of Some New Heterocycles Derived from Phenylacetyl Isothiocyanate. Chinese Journal of Chemistry, 26 (2), 388–391. doi: http://doi.org/10.1002/cjoc.200890074
- Ismail, M. F., Elsayed, G. A. (2018). Dodecanoyl isothiocyanate and N′-(2-cyanoacetyl) dodecanehydrazide as precursors for the synthesis of different heterocyclic compounds with interesting antioxidant and antitumor activity. Synthetic Communications, 48 (8), 892–905. doi: http://doi.org/10.1080/00397911.2018.1428345
- Abdel Hamid, A. M. (2019). Addition–cyclization reactions of furan-2-carbonyl isothiocyanate with nitrogen nucleophiles as a synthetic route to novel azines and azoles of potential biological activity. Journal of the Iranian Chemical Society, 16 (9), 1853–1861. doi: http://doi.org/10.1007/s13738-019-01659-6
- Zhong, B., Al-Awar, R. S., Shih, C., Grimes, J. H., Vieth, M., Hamdouchi, C. (2006). Novel route to the synthesis of 4-quinolyl isothiocyanates. Tetrahedron Letters, 47 (13), 2161–2164. doi: http://doi.org/10.1016/j.tetlet.2006.01.119
- Beauchemin, A., Vincent-Rocan, J.-F. (2016). N-Isocyanates, N-Isothiocyanates and Their Masked/Blocked Derivatives: Synthesis and Reactivity. Synthesis, 48 (21), 3625–3645. doi: http://doi.org/10.1055/s-0036-1588066
- Entezari, N., Akhlaghinia, B., Rouhi-Saadabad, H. (2014). Direct and Facile Synthesis of Acyl Isothiocyanates from Carboxylic Acids Using Trichloroisocyanuric Acid/Triphenylphosphine System. Croatica Chemica Acta, 87 (3), 201–206. doi: http://doi.org/10.5562/cca2381
- Saeed, A., Mustafa, M. N., Zain-ul-Abideen, M., Shabir, G., Erben, M. F., Flörke, U. (2018). Current developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3- (substituted)thioureas: advances Continue …. Journal of Sulfur Chemistry, 40 (3), 312–350. doi: http://doi.org/10.1080/17415993.2018.1551488
- Lapasam, A., Kollipara, M. R. (2020). A survey of crystal structures and biological activities of platinum group metal complexes containing N-acylthiourea ligands. Phosphorus, Sulfur, and Silicon and the Related Elements, 195 (10), 779–804. doi: http://doi.org/10.1080/10426507.2020.1764956
- Saeed, A., Shakil Shah, M., Ali Larik, F., Ullah Khan, S., Ali Channar, P., Flörke, U., Iqbal, J. (2017). Synthesis, computational studies and biological evaluation of new 1-acetyl-3-aryl thiourea derivatives as potent cholinesterase inhibitors. Medicinal Chemistry Research, 26 (8), 1635–1646. doi: http://doi.org/10.1007/s00044-017-1829-6
- Tahir, S., Badshah, A., Hussain, R. A., Tahir, M. N., Tabassum, S., Patujo, J. A., Rauf, M. K. (2015). DNA-binding studies and biological activities of new nitrosubstituted acyl thioureas. Journal of Molecular Structure, 1099, 215–225. doi: http://doi.org/10.1016/j.molstruc.2015.06.024
- Larik, F. A., Saeed, A., Faisal, M., Channar, P. A., Azam, S. S., Ismail, H. Et. al. (2018). Synthesis, molecular docking and comparative efficacy of various alkyl/aryl thioureas as antibacterial, antifungal and α-amylase inhibitors. Computational Biology and Chemistry, 77, 193–198. doi: http://doi.org/10.1016/j.compbiolchem.2018.10.007
- Al-Amily, D. H., Hassan Mohammed, M. (2019). Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group. Scientia Pharmaceutica, 87 (4), 28. doi: http://doi.org/10.3390/scipharm87040028
- Dobrikov, G. M., Valcheva, V., Nikolova, Y., Ugrinova, I., Pasheva, E., Dimitrov, V. (2013). Efficient synthesis of new (R)-2-amino-1-butanol derived ureas, thioureas and acylthioureas and in vitro evaluation of their antimycobacterial activity. European Journal of Medicinal Chemistry, 63, 468–473. doi: http://doi.org/10.1016/j.ejmech.2013.02.034
- Antypenko, L., Meyer, F., Kholodniak, O., Sadykova, Z., Jirásková, T., Troianova, A. et. al. (2018). Novel acyl thiourea derivatives: Synthesis, antifungal activity, gene toxicity, drug-like and molecular docking screening. Archiv Der Pharmazie, 352 (2), 1800275. doi: http://doi.org/10.1002/ardp.201800275
- Kholodniak, O. V., Kazunin, M. S., Meyer, F., Kovalenko, S. I., Steffens, K. G. (2020). Novel N-cycloalkylcarbonyl-N-arylthioureas: Synthesis, Design, Antifungal Activity and Gene Toxicity. Chemistry and Biodiversity, 17 (7), е2000212. doi: http://doi.org/10.1002/cbdv.202000212
- Kholodniak, O. V., Stavytskyi, V. V., Kovalenko, S. I. (2021). Substituted (сycloalkylcarbonylthioureido)aryl-(benzyl-)carboxylic(sulfonic) acids: synthesis, antimicrobial and growth-regulating activity. Current Issues in Pharmacy and Medicine: Science and Practice, 14 (1), 4–11. doi: http://doi.org/10.14739/2409-2932.2021.1.226726
- Kholodniak, O. V., Sokolova, K. V., Kovalenko, S. I., Podpletnya, O. A. (2020). Directed search for compounds that affect the excretory function of rat kidneys, among new cycloalkylcarbonyl thioureas and thiosemicarbazides derivatives. Medical and Clinical Chemistry, 22 (2), 5–16. doi: http://doi.org/10.11603/mcch.2410-681x.2020.v.i2.11351
- Kholodniak, O. V., Stavytskyi, V. V., Kazunin, M. S., Bukhtiayrova, N. V., Berest, G. G., Belenichev, I. F., Kovalenko, S. I. (2021). Design, synthesis and anticonvulsant activity of new Diacylthiosemicarbazides. Biopolymers and Cell, 37 (2), 125–142. doi: http://doi.org/10.7124/bc.000a46
- Haribabu, J., Subhashree, G. R., Saranya, S., Gomathi, K., Karvembu, R., Gayathri, D. (2015). Synthesis, crystal structure, and in vitro and in silico molecular docking of novel acyl thiourea derivatives. Journal of Molecular Structure, 1094, 281–291. doi: http://doi.org/10.1016/j.molstruc.2015.03.035
- Banaei, A., Shiran, J. A., Saadat, A., Ardabili, F. F., McArdle, P. (2015). One-pot and two-step synthesis of novel carbonylthioureas and dicarbonyldithioureas derivatives. Journal of Molecular Structure, 1099, 427–431. doi: http://doi.org/10.1016/j.molstruc.2015.06.074
- Mustafa, M. N., Saeed, A., Channar, P. A., Larik, F. A., Zain-ul abideen, M., Shabir, G. et. al. (2019). Synthesis, molecular docking and kinetic studies of novel quinolinyl based acyl thioureas as mushroom tyrosinase inhibitors and free radical scavengers. Bioorganic Chemistry, 90, 103063. doi: http://doi.org/10.1016/j.bioorg.2019.103063
- Rao, X.-P., Wu, Y., Song, Z.-Q., Shang, S.-B., Wang, Z.-D. (2010). Synthesis and antitumor activities of unsymmetrically disubstituted acylthioureas fused with hydrophenanthrene structure. Medicinal Chemistry Research, 20 (3), 333–338. doi: http://doi.org/10.1007/s00044-010-9303-8
- Rauf, M. K., Zaib, S., Talib, A., Ebihara, M., Badshah, A., Bolte, M., Iqbal, J. (2016). Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N′-disubstituted thioureas derived from 3-chlorobenzoic acid. Bioorganic & Medicinal Chemistry, 24 (18), 4452–4463. doi: http://doi.org/10.1016/j.bmc.2016.07.042
- Pete, U. D., Zade, C. M., Bhosale, J. D., Tupe, S. G., Chaudhary, P. M., Dikundwar, A. G., Bendre, R. S. (2012). Hybrid molecules of carvacrol and benzoyl urea/thiourea with potential applications in agriculture and medicine. Bioorganic & Medicinal Chemistry Letters, 22 (17), 5550–5554. doi: http://doi.org/10.1016/j.bmcl.2012.07.017
- Burgeson, J. R., Moore, A. L., Boutilier, J. K., Cerruti, N. R., Gharaibeh, D. N., Lovejoy, C. E. et. al. (2012). SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity. Bioorganic & Medicinal Chemistry Letters, 22 (13), 4263–4272. doi: http://doi.org/10.1016/j.bmcl.2012.05.035
- Abd Halim, A. N., Ngaini, Z. (2017). Synthesis and characterization of halogenated bis(acylthiourea) derivatives and their antibacterial activities. Phosphorus, Sulfur, and Silicon and the Related Elements, 192 (9), 1012–1017. doi: http://doi.org/10.1080/10426507.2017.1315421
- Khairul M. W., Ariffin A., Ismail N., Daud, A. (2016). Synthesis, Spectroscopic Studies, and Biological Activities of Acylthiourea Derivatives as Potential Anti-Bacteria Agents. EDUCATUM Journal of Science, Mathematics and Technology, 3(1), 13-19.
- Li, S., Li, H., Cao, X., Chen, C. (2013). Synthesis and Bio-Evaluation of Novel Salicylic Acid-Oriented Thiourea Derivatives with Potential Applications in Agriculture. Letters in Drug Design & Discovery, 11 (1), 98–103. doi: http://doi.org/10.2174/15701808113109990045
- El-Gaby, M. S. A., Hussein, M. F., Hassan, M. I., Ali, A. M., Elshaier, Y. A. M. M., Gebril, A. S., Faraghally, F. A. (2018). New sulfonamide hybrids: synthesis, in vitro antimicrobial activity and docking study of some novel sulfonamide derivatives bearing carbamate/acyl-thiourea scaffolds. Mediterranean Journal of Chemistry, 7 (5), 370–385. doi: http://doi.org/10.13171/mjc751912111445mh
- Sajid-ur-Rehman, Saeed, A., Saddique, G., Ali Channar, P., Ali Larik, F., Abbas, Q. et. al. (2018). Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, pharmacokinetic properties, lead optimization, Lineweaver-Burk plot evaluation and binding analysis. Bioorganic & Medicinal Chemistry, 26 (12), 3707–3715. doi: http://doi.org/10.1016/j.bmc.2018.06.002
- Koca, İ., Özgür, A., Coşkun, K. A., Tutar, Y. (2013). Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorganic & Medicinal Chemistry, 21 (13), 3859–3865. doi: http://doi.org/10.1016/j.bmc.2013.04.021
- Nitulescu, G. M., Draghici, C., Chifiriuc, M. C., Marutescu, L., Bleotu, C., Missir, A. V. (2010). Synthesis and antimicrobial screening of N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives. Medicinal Chemistry Research, 21 (3), 308–314. doi: http://doi.org/10.1007/s00044-010-9541-9
- Sun, N., Shen, Z., Zhai, Z., Han, L., Weng, J., Tan, C., Liu, X. (2017). Design,Synthesis,Fungicidal Activity and Docking Study of Acyl Thiourea Derivatives Containing Pyrazole Moiety. Chinese Journal of Organic Chemistry, 37 (10), 2710. doi: http://doi.org/10.6023/cjoc201704032
- Min, L.-J., Zhai, Z.-W., Shi, Y.-X., Han, L., Tan, C.-X., Weng, J.-Q. et. al. (2019). Synthesis and biological activity of acyl thiourea containing difluoromethyl pyrazole motif. Phosphorus, Sulfur, and Silicon and the Related Elements, 195 (1), 22–28. doi: http://doi.org/10.1080/10426507.2019.1633530
- Zhang, J.-F., Xu, J.-Y., Wang, B.-L., Li, Y.-X., Xiong, L.-X., Li, Y.-Q. et. al. (2012). Synthesis and Insecticidal Activities of Novel Anthranilic Diamides Containing Acylthiourea and Acylurea. Journal of Agricultural and Food Chemistry, 60 (31), 7565–7572. doi: http://doi.org/10.1021/jf302446c
- Koca, İ., Özgür, A., Er, M., Gümüş, M., Açikalin Coşkun, K., Tutar, Y. (2016). Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis. European Journal of Medicinal Chemistry, 122, 280–290. doi: http://doi.org/10.1016/j.ejmech.2016.06.032
- Plutín, A. M., Ramos, R., Mocelo, R., Alvarez, A., Castellano, E. E., Cominetti, M. R. et. al. (2020). Antitumor activity of Pd(II) complexes with N,S or O,S coordination modes of acylthiourea ligands. Polyhedron, 184, 114543. doi: http://doi.org/10.1016/j.poly.2020.114543
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