Biologically oriented synthesis of medicines (BIODS) based on heterylpoxid 2,5- disubstituted 1,3,4-oxadiazoles (Part 1)

Authors

DOI:

https://doi.org/10.14739/2409-2932.2020.2.207211

Keywords:

1, 3, 4-oxadiazoles, BIODS, antitumor activity, antifungal agents, anti-tuberculosis agents, antimalarial, antibacterial agents

Abstract

 

At the present stage of development of medical chemistry, many basic synthetic approaches to the synthesis of 1,3,4-oxadiazole structures are known, which are focused mainly on the principles of combinatorial chemistry with a wide range of biological activity.

The aim of the work was searching, systematizing, and generalizing literature sources for biologically oriented drug synthesis (BIODS) based on hetero derivatives of 2,5 disubstituted 1,3,4-oxadiazoles.

Heterocyclic systems containing a 1,3,4-oxadiazole nucleus have a rich synthetic history and are characterized by a wide range of synthesis methods. The review article firstly summarizes the literature on the chemistry of hetero derivatives of 2,5 disubstituted 1,3,4-oxadiazoles as important synthetic substrates and precursors for biologically oriented synthesis. The most classical methods of obtaining, which are the intramolecular dehydration of 1,2-diacylhydrazines, the interaction of hydrazyl carboxylic acid hydrazides with carbon disulfide and the formation of the oxadiazole nucleus by microwave synthesis are considered. It is worth noting that the processes of heterofunctionalization are new in the chemistry of 1,3,4-oxadiazoles and allow us to obtain new bio-promising hybrid structures. Significant emphasis is placed on synthesized compounds with pronounced antitumor, antifungal, antituberculous, antimalarial and antibacterial activities, and structure – action dependencies. Possible modern mechanisms of action of the corresponding activity, which are inhibition of enzymes, cytotoxicity, apoptosis, etc., are analyzed in detail.

Conclusions. The original works concerning the methods of synthesis of hetero derivatives of 2,5-disubstituted 1,3,4-oxadiazoles with pronounced antitumor, antifungal, antituberculous, antimalarial and antibacterial activities were generalized and systematized. The analysis of the presented material was shown the importance and real perspective of biologically oriented synthesis of drugs in this segment of the chemistry of nitrogen-containing heterocycles.

 

References

  1. Sun, S. Y., Jia, Q., & Zhang, Z. H. (2019). Applications of amide isosteres in medicinal chemistry. Bioorganic & Medicinal Chemistry Letters, 29(18), 2535-2550. https://doi.org/10.1016/j.bmcl.2019.07.033
  2. Suaifan, G., & Mohammed, A. A. M. (2019). Fluoroquinolones structural and medicinal developments (2013-2018): Where are we now? Bioorganic & Medicinal Chemistry, 27(14), 3005-3060. https://doi.org/10.1016/j.bmc.2019.05.038
  3. Rego, Y. F., Queiroz, M. P., Brito, T. O., Carvalho, P. G., de Queiroz, V. T., de Fatima, A., & Macedo, F. (2018). A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria. Journal of Advanced Research, 13, 69-100. https://doi.org/10.1016/j.jare.2018.05.003
  4. Chandrika, K., & Sharma, S. (2020). Promising antifungal agents: A minireview. Bioorganic & Medicinal Chemistry, 28(7), Article 115398. https://doi.org/10.1016/j.bmc.2020.115398
  5. Nicola, A. M., Albuquerque, P., Paes, H. C., Fernandes, L., Costa, F. F., Kioshima, E. S., Abadio, A. K. R., Bocca, A. L., & Felipe, M. S. (2019). Antifungal drugs: New insights in research & development. Pharmacology & Therapeutics, 195, 21-38. https://doi.org/10.1016/j.pharmthera.2018.10.008
  6. Jacob, P. J., Manju, S. L., Ethiraj, K. R., & Elias, G. (2018). Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach. European Journal of Pharmaceutical Sciences, 121, 356-381. https://doi.org/10.1016/j.ejps.2018.06.003
  7. Nanjan, M. J., Mohammed, M., Kumar, B. R. P., & Chandrasekar, M. J. N. (2018). Thiazolidinediones as antidiabetic agents: A critical review. Bioorganic Chemistry, 77, 548-567. https://doi.org/10.1016/j.bioorg.2018.02.009
  8. Kerru, N., Singh-Pillay, A., Awolade, P., & Singh, P. (2018). Current anti-diabetic agents and their molecular targets: A review. European Journal of Medicinal Chemistry, 152, 436-488. https://doi.org/10.1016/j.ejmech.2018.04.061
  9. Gao, F., Zhang, X., Wang, T. F., & Xiao, J. Q. (2019). Quinolone hybrids and their anti-cancer activities: An overview. European Journal of Medicinal Chemistry, 165, 59-79. https://doi.org/10.1016/j.ejmech.2019.01.017
  10. Liang, X. X., Wu, Q., Luan, S. X., Yin, Z. Q., He, C. L., Yin, L. Z., Zou, Y. F., Yuan, Z. X., Li, L. X., Song, X., He, M., Lv, C., & Zhang, W. (2019). A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. European Journal of Medicinal Chemistry, 171, 129-168. https://doi.org/10.1016/j.ejmech.2019.03.034
  11. Xu, Z., Zhao, S. J., & Liu, Y. (2019). 1,2,3-Triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms and structure-activity relationships. European Journal of Medicinal Chemistry, 183, Article 111700. https://doi.org/10.1016/j.ejmech.2019.111700
  12. Campanico, A., Moreira, R., & Lopes, F. (2018). Drug discovery in tuberculo-sis. New drug targets and antimycobacterial agents. European Journal of Medicinal Chemistry, 150, 525-545. https://doi.org/10.1016/j.ejmech.2018.03.020
  13. Sharma, V., Bhatia, P., Alam, O., Naim, M. J., Nawaz, F., Sheikh, A. A., & Jha, M. (2019). Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008-2019). Bioorganic Chemistry, 89, Article Unsp 103007. https://doi.org/10.1016/j.bioorg.2019.103007
  14. Silva, V. L. M., Elguero, J., & Silva, A. M. S. (2018). Current progress on antioxidants incorporating the pyrazole core. European Journal of Medicinal Chemistry, 156, 394-429. https://doi.org/10.1016/j.ejmech.2018.07.007
  15. De, S. S., Khambete, M. P., & Degani, M. S. (2019). Oxadiazole scaffolds in anti-tuberculosis drug discovery. Bioorganic & Medicinal Chemistry Letters, 29(16), 1999-2007. https://doi.org/10.1016/j.bmcl.2019.06.054
  16. Karpenko, Y. V., Omelyanchik, L. O., Samura, Т. А., & Omelyanchik, V. N. (2018). Syntez ta doslidzhennia zalezhnosti “struktura – hostra toksychnist” novykh hibrydiv 1,3,4-oksadiazol-2-tionu z akrydyn-9(10H)-onom [Synthesis and study of the “acute toxicity vs. structure” dependence of new hybrid 1,3,4-oxadiazole-2-thione with acridine-9(10H)-one]. Voprosy khimii i khimicheskoi tekhnologii, (4), 5-13. [in Ukrainian].
  17. Zhang, J. L., Wang, X. M., Yang, J. F., Guo, L. N., Wang, X. L., Song, B., Dong, W., & Wang, W. B. (2020). Novel diosgenin derivatives containing 1,3,4-oxadiazole/thiadiazole moieties as potential antitumor agents: Design, synthesis and cytotoxic evaluation. European Journal of Medicinal Chemistry, 186, Article Unsp 111897. https://doi.org/10.1016/j.ejmech.2019.111897
  18. Sreenivasulu, R., Tej, M. B., Jadav, S. S., Sujitha, P., Kumar, C. G., & Raju, R. R. (2020). Synthesis, anticancer evaluation and molecular docking studies of 2,5-bis(indolyl)-1,3,4-oxadiazoles, Nortopsentin analogues. Journal of Molecular Structure, 1208, Article 127875. https://doi.org/10.1016/j.molstruc.2020.127875
  19. Asati, V., & Bharti, S. K. (2018). Design, synthesis and molecular modeling studies of novel thiazolidine-2,4-dione derivatives as potential anti-cancer agents. Journal of Molecular Structure, 1154, 406-417. https://doi.org/10.1016/j.molstruc.2017.10.077
  20. Zhou, K., Liu, J. C., Xiong, X. Q., Cheng, M., Hu, X. L., Narva, S., Zhao, X. Y., Wu, Y. L., & Zhang, W. (2019). Design, synthesis of 4,5-diazafluorene derivatives and their anticancer activity via targeting telomeric DNA G-quadruplex. European Journal of Medicinal Chemistry, 178, 484-499. https://doi.org/10.1016/j.ejmech.2019.06.012
  21. Caneschi, W., Enes, K. B., de Mendonca, C. C., Fernandes, F. D., Mi-guel, F. B., Martins, J. D., Le Hyaric, M., Pinho, R. R., Duarte, L. M., de Oliveira, M. A. L., Dos Santos, H. F., Lopes, M. T. P., Dittz, D., Silva, H., & Couri, M. R. C. (2019). Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles. European Journal of Medicinal Chemistry, 165, 18-30. https://doi.org/10.1016/j.ejmech.2019.01.001
  22. Dhawan, S., Kerru, N., Awolade, P., Singh-Pillay, A., Saha, S. T., Kaur, M., Jonnalagadda, S. B., & Shing, P. (2018). Synthesis, computational studies and antiproliferative activities of coumarin-tagged 1,3,4-oxadiazole conjugates against MDA-MB-231 and MCF-7 human breast cancer cells. Bioorganic & Medicinal Chemistry, 26(21), 5612-5623. https://doi.org/10.1016/j.bmc.2018.10.006
  23. Narella, S. G., Shaik, M. G., Mohammed, A., Alvala, M., Angeli, A., & Supuran, C. T. (2019). Synthesis and biological evaluation of coumarin-1,3,4-oxadiazole hybrids as selective carbonic anhydrase IX and XII inhibitors. Bioorganic Chemistry, 87, 765-772. https://doi.org/10.1016/j.bioorg.2019.04.004
  24. Taha, M., Rashid, U., Imran, S., & Ali, M. (2018). Rational design of bis-indolylmethane-oxadiazole hybrids as inhibitors of thymidine phosphorylase. Bioorganic & Medicinal Chemistry, 26(12), 3654-3663. https://doi.org/10.1016/j.bmc.2018.05.046
  25. El-Sayed, N. A., Nour, M. S., Salem, M. A., & Arafa, R. K. (2019). New oxadiazoles with selective-COX-2 and EGFR dual inhibitory activity: Design, synthesis, cytotoxicity evaluation and in silico studies. European Journal of Medicinal Chemistry, 183, Article 111693. https://doi.org/10.1016/j.ejmech.2019.111693
  26. Karpenko, Y. V., & Omelyanchik, L. O. (2017). Syntez heterylopokhidnykh 2,5-dyzamishchenykh 1,3,4-oksadiazoliv [Synthesis of heteryl derivatives of 2,5-disubstituted 1,3,4-okasadiazole]. Journal of Organic and Pharmaceutical Chemistry, 15(4), 21-32. [in Ukrainian]. https://doi.org/10.24959/ophcj.17.917
  27. Desai, N. C., & Dodiya, A. M. (2014). Synthesis, characterization and in vitro antimicrobial screening of quinoline nucleus containing 1,3,4-oxadiazole and 2-azetidinone derivatives. Journal of Saudi Chemical Society, 18(5), 425-431. https://doi.org/10.1016/j.jscs.2011.09.005
  28. Hannoun, M. H., Hagras, M., Kotb, A., El-Attar, A., & Abulkhair, H. S. (2020). Synthesis and antibacterial evaluation of a novel library of 2-(thiazol-5-yl)-1,3,4-oxadiazole derivatives against methicillin-resistant Staphylococcus aureus (MRSA). Bioorganic Chemistry, 94, Article 103364. https://doi.org/10.1016/j.bioorg.2019.103364
  29. Hagras, M., Hegazy, Y. A., Elkabbany, A. H., Mohammad, H., Ghiaty, A., Abdelghany, T. M., Seleem, M. N., & Mayhoub, A. S. (2018). Biphenylthiazole antibiotics with an oxadiazole linker: An approach to improve physicochemical properties and oral bioavailability. European Journal of Medicinal Chemistry, 143, 1448-1456. https://doi.org/10.1016/j.ejmech.2017.10.048
  30. Guo, Y., Xu, T., Bao, C. N., Liu, Z. Y., Fan, J. P., Yang, R. G., & Qin, S. S. (2019). Design and synthesis of new norfloxacin-1,3,4-oxadiazole hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). European Journal of Pharmaceutical Sciences, 136, Article Unsp 104966. https://doi.org/10.1016/j.ejps.2019.104966
  31. Zhu, H. H., Zeng, D., Wang, M. W., Wang, P. Y., Wu, Y. Y., Liu, L. W., & Yang, S. (2020). Integration of naturally bioactive thiazolium and 1,3,4-oxadiazole fragments in a single molecular architecture as prospective antimicrobial surrogates. Journal of Saudi Chemical Society, 24(1), 127-138. https://doi.org/10.1016/j.jscs.2019.10.002
  32. Reddy, G. M., Garcia, J. R., Reddy, V. H., Kumari, A. K., Zyryanov, G. V., & Yuvaraja, G. (2019). An efficient and green approach: One pot, multi component, reusable catalyzed synthesis of pyranopyrazoles and investigation of biological assays. Journal of Saudi Chemical Society, 23(3), 263-273. https://doi.org/10.1016/j.jscs.2018.07.003
  33. Ahadi, H., & Emami, S. (2020). Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: Synthesis and in vitro studies. European Journal of Medicinal Chemistry, 187, Article Unsp 111970. https://doi.org/10.1016/j.ejmech.2019.111970
  34. Sekhar, M. M., Nagarjuna, U., Padmavathi, V., Padmaja, A., Reddy, N. V., & Vijaya, T. (2018). Synthesis and antimicrobial activity of pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. European Journal of Medicinal Chemistry, 145, 1-10. https://doi.org/10.1016/j.ejmech.2017.12.067
  35. Wang, X. B., Hu, H. R. A., Zhao, X., Chen, M., Zhang, T. T., Geng, C. W., Mei, Y. D., Lu, A. M., & Yang, C. L. (2019). Novel quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety as potential bactericides and fungicides: Design, synthesis, characterization and 3D-QSAR analysis. Journal of Saudi Chemical Society, 23(8), 1144-1156. https://doi.org/10.1016/j.jscs.2019.07.006
  36. Gonzalez-Lara, M. F., Sifuentes-Osornio, J., & Ostrosky-Zeichner, L. (2017). Drugs in Clinical Development for Fungal Infections. Drugs, 77(14), 1505-1518. https://doi.org/10.1007/s40265-017-0805-2
  37. Odds, F. C., Brown, A. J. P., & Gow, N. A. R. (2003). Antifungal agents: mechanisms of action. Trends in Microbiology, 11(6), 272-279. https://doi.org/10.1016/s0966-842x(03)00117-3
  38. Hamann, A., Brust, D., & Osiewacz, H. D. (2008). Apoptosis pathways in fungal growth, development and ageing. Trends in Microbiology, 16(6), 276-283. https://doi.org/10.1016/j.tim.2008.03.003
  39. Qi, G. F., Zhu, F. Y., Du, P., Yang, X. F., Qiu, D. W., Yu, Z. N., Chen, J. Y., & Zhao, X. Y. (2010). Lipopeptide induces apoptosis in fungal cells by a mitochondria-dependent pathway. Peptides, 31(11), 1978-1986. https://doi.org/10.1016/j.peptides.2010.08.003
  40. Emrick, D., Ravichandran, A., Gosai, J., Lu, S., Gordon, D. M., & Smith, L. (2013). The Antifungal Occidiofungin Triggers an Apoptotic Mechanism of Cell Death in Yeast. Journal of Natural Products, 76(5), 829-838. https://doi.org/10.1021/np300678e
  41. Cavusoglu, B. K., Yurtta, L., & Canturk, Z. (2018). The synthesis, antifungal and apoptotic effects of triazole-oxadiazoles against Candida species. European Journal of Medicinal Chemistry, 144, 255-261. https://doi.org/10.1016/j.ejmech.2017.12.020
  42. Karaburun, A. C., Cavusoglu, B. K., Cevik, U. A., Osmaniye, D., Saglik, B. N., Levent, S., Ozkay, Y., Atli, O., Koparal, A. S., & Kaplancikli, Z. A. (2019). Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds. Molecules, 24(1), Article 191. https://doi.org/10.3390/molecules24010191
  43. Kummari, L. K., Butler, M. S., Furlong, E., Blundell, R., Nouwens, A., Silva, A. B., Kappler, U., Fraser, J. A., Kobe, B., Cooper, M. A., & Robertson, A. A. B. (2018). Antifungal benzo b thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles. Bioorganic & Medicinal Chemistry, 26(20), 5408-5419. https://doi.org/10.1016/j.bmc.2018.09.004
  44. Macaev, F., Ribkovskaia, Z., Pogrebnoi, S., Boldescu, V., Rusu, G., Shvets, N., Dimoglo, A., Geronikaki, A., & Reynolds, R. (2011). The structure-antituberculosis activity relationships study in a series of 5-aryl-2-thio-1,3,4-oxadiazole derivatives. Bioorganic & Medicinal Chemistry, 19(22), 6792-6807. https://doi.org/10.1016/j.bmc.2011.09.038
  45. Ambhore, A. N., Kamble, S. S., Kadam, S. N., Kamble, R. D., Hebade, M. J., Hese, S. V., Gaikwad, M. V., Meshram, R. J., Gacche, R. N., & Dawane, B. S. (2019). Design, synthesis and in silico study of pyridine based 1,3,4-oxadiazole embedded hydrazinecarbothioamide derivatives as potent anti-tubercular agent. Computational Biology and Chemistry, 80, 54-65. https://doi.org/10.1016/j.compbiolchem.2019.03.002
  46. Verma, G., Chashoo, G., Ali, A., Khan, M. F., Akhtar, W., Ali, I., Akhtar, M., Alam, M. M., & Shaquiquzzaman, M. (2018). Synthesis of pyrazole acrylic acid based oxadiazole and amide derivatives as antimalarial and anticancer agents. Bioorganic Chemistry, 77, 106-124. https://doi.org/10.1016/j.bioorg.2018.01.007
  47. Verma, G., Khan, M. F., Nainwal, L. M., Ishaq, M., Akhter, M., Bakht, A., Anwer, T., Afrin, F., Islamuddin, M., Husain, I., Alam, M. M., & Shaquiquzzaman, M. (2019). Targeting malaria and leishmaniasis: Synthesis and pharmacological evaluation of novel pyrazole-1,3,4-oxadiazole hybrids. Part II. Bioorganic Chemistry, 89, Article Unsp 102986. https://doi.org/10.1016/j.bioorg.2019.102986
  48. Mahesh, R., Mundra, S., Devadoss, T., & Kotra, L. P. (2019). Design, synthesis and evaluation of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives as a new class of falcipain-2 inhibitors. Arabian Journal of Chemistry, 12(7), 1436-1446. https://doi.org/10.1016/j.arabjc.2014.11.008
  49. Marques, A. F., Esser, D., Rosenthal, P. J., Kassack, M. U., & Lima, L. (2013). Falcipain-2 inhibition by suramin and suramin analogues. Bioorganic & Medicinal Chemistry, 21(13), 3667-3673. https://doi.org/10.1016/j.bmc.2013.04.047
  50. Micale, N., Ettari, R., Schirmeister, T., Evers, A., Gelhaus, C., Leippe, M., Zappala, M., & Grasso, S. (2009). Novel 2H-isoquinolin-3-ones as antiplasmodial falcipain-2 inhibitors. Bioorganic & Medicinal Chemistry, 17(18), 6505-6511. https://doi.org/10.1016/j.bmc.2009.08.013
  51. Cotrin, S. S., Gouvea, I. E., Melo, P. M. S., Bagnaresi, P., Assis, D. M., Araujo, M. S., Juliano, M. A., Gazarini, M. L., Rosenthal, P. J., Juliano, L., & Carmona, A. K. (2013). Substrate specificity studies of the cysteine peptidases falcipain-2 and falcipain-3 from Plasmodium falciparum and demonstration of their kininogenase activity. Molecular and Biochemical Parasitology, 187(2), 111-116. https://doi.org/10.1016/j.molbiopara.2013.01.002
  52. Rizzi, L., Sundararaman, S., Cendic, K., Vaiana, N., Korde, R., Sinha, D., Mohmmed, A., Malhotra, P., & Romeo, S. (2011). Design and synthesis of protein-protein interaction mimics as Plasmodium falciparum cysteine protease, falcipain-2 inhibitors. European Journal of Medicinal Chemistry, 46(6), 2083-2090. https://doi.org/10.1016/j.ejmech.2011.02.061

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Karpenko YV, Panasenko OI, Knysh YH. Biologically oriented synthesis of medicines (BIODS) based on heterylpoxid 2,5- disubstituted 1,3,4-oxadiazoles (Part 1). Current issues in pharmacy and medicine: science and practice [Internet]. 2020Jul.3 [cited 2026Jun.26];13(2). Available from: https://pharmed.zsmu.edu.ua/article/view/207211

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Vol. 13 No. 2 (2020)

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