Abstract
Background: Tumor plasticity processes impact the treatment of different types of cancer; as an effect of this, the bioprospecting of therapies from natural and/or synthetic compounds that can regulate or modulate the immune system has increased considerably. Oxadiazole derivatives are structures that exhibit diverse biological activities. Therefore, this review aimed to evaluate the activity of oxadiazole compounds against tumor cell lines and their possible immune-mediated mechanisms.
Methods: A search in PubMed, Web of Science, and Science Direct databases was carried out on studies published from January 1, 2004, to January 31, 2022, using “oxadiazole” in combination with the other descriptors “cancer” and “macrophage”. Only experimental in vitro and in vivo articles were included. A similar search strategy was used in the Derwent Innovation Index database for technology mapping. The search was performed on Drugbank using the descriptor oxadiazole for commercial mapping.
Results: 23 oxadiazole studies were included in this review, and some biological activities linked to antitumoral and immunomodulation were listed. Oxadiazole derivatives inhibited tumor cell growth and proliferation, blocked cell cycle, modulated mitochondrial membrane potential, presented immunoregulatory activity by different mechanisms reducing proinflammatory cytokines levels and acted directly as selective inhibitors of the COX enzyme. There was an increase in oxadiazole patent publications in the last 11 years, with emphasis on chemistry, pharmacy and biotechnology applied to microbiology areas. Compounds with 1,2,4-oxadiazole isomer are predominant in patent publications and approved drugs as observed in the technological and commercial mapping.
Conclusion: Therefore, oxadiazole derivatives are therapeutic molecules that can be considered promising for the development of cancer therapies.
Keywords: Oxadiazoles, Cancer, Immunomodulation, Inflammatory mediators, Macrophages, Chemotherapy
[http://dx.doi.org/10.1055/s-0040-1713911] [PMID: 33254272]
[http://dx.doi.org/10.3390/cells9102308] [PMID: 33081387]
[http://dx.doi.org/10.1126/science.aaw5473] [PMID: 32273439]
[http://dx.doi.org/10.1155/2020/5825401] [PMID: 33282961]
[http://dx.doi.org/10.1038/s41573-018-0006-z] [PMID: 30622344]
[http://dx.doi.org/10.1038/s41423-020-0488-6] [PMID: 32612154]
[http://dx.doi.org/10.3390/ijms20143483] [PMID: 31315181]
[http://dx.doi.org/10.1080/10406638.2021.1886123]
[http://dx.doi.org/10.1021/ol200234r] [PMID: 21506595]
[http://dx.doi.org/10.3390/ijms23031596] [PMID: 35163522]
[http://dx.doi.org/10.4103/1735-5362.212051] [PMID: 28855945]
[http://dx.doi.org/10.1186/2191-2858-2-8] [PMID: 22380426]
[http://dx.doi.org/10.1186/s40199-015-0139-0] [PMID: 26739353]
[http://dx.doi.org/10.1016/j.bioorg.2016.02.007]
[http://dx.doi.org/10.1016/j.ejmech.2017.05.018] [PMID: 28494251]
[http://dx.doi.org/10.1016/j.ejmech.2017.11.003] [PMID: 29129514]
[http://dx.doi.org/10.1080/14756366.2020.1740696] [PMID: 32183548]
[http://dx.doi.org/10.3390/ijms21103511] [PMID: 32429154]
[http://dx.doi.org/10.1016/j.bmc.2013.11.004] [PMID: 24286761]
[http://dx.doi.org/10.1016/j.molstruc.2021.132218]
[http://dx.doi.org/10.4103/0253-7613.140584] [PMID: 25298582]
[http://dx.doi.org/10.1016/j.bioorg.2017.06.003] [PMID: 28738249]
[http://dx.doi.org/10.1016/j.ejmech.2021.113693] [PMID: 34315041]
[http://dx.doi.org/10.1016/j.cbi.2015.08.018] [PMID: 26335192]
[http://dx.doi.org/10.1016/j.bmcl.2020.127373] [PMID: 32738985]
[http://dx.doi.org/10.1080/14756366.2021.1908277] [PMID: 33957835]
[http://dx.doi.org/10.1016/j.bmcl.2011.11.046] [PMID: 22153340]
[http://dx.doi.org/10.1016/j.ejmech.2019.06.037] [PMID: 31233921]
[http://dx.doi.org/10.7150/thno.44523] [PMID: 32685002]
[http://dx.doi.org/10.1111/bph.14351] [PMID: 29722898]
[http://dx.doi.org/10.1039/C5PY01335F]
[http://dx.doi.org/10.1007/s11427-018-9461-5] [PMID: 30900169]
[http://dx.doi.org/10.3389/fcell.2021.786728] [PMID: 34917620]
[http://dx.doi.org/10.3390/antib10010010] [PMID: 33803078]
[http://dx.doi.org/10.1016/j.bmcl.2009.05.052] [PMID: 19500976]
[http://dx.doi.org/10.1016/j.ejmech.2010.07.012] [PMID: 20705365]
[http://dx.doi.org/10.1016/j.bmcl.2014.07.089] [PMID: 25155551]
[http://dx.doi.org/10.1021/jm300100d] [PMID: 22435708]
[http://dx.doi.org/10.1016/j.ejmech.2015.04.051] [PMID: 25965776]
[http://dx.doi.org/10.1007/s00018-016-2451-3] [PMID: 28083595]
[http://dx.doi.org/10.1038/cr.2017.155] [PMID: 29219147]
[http://dx.doi.org/10.1016/j.bioorg.2016.09.002] [PMID: 27656775]
[http://dx.doi.org/10.1002/cmdc.201402189] [PMID: 24976143]
[http://dx.doi.org/10.1007/s10495-017-1410-2] [PMID: 28840369]
[http://dx.doi.org/10.2147/JIR.S333451] [PMID: 35002275]
[http://dx.doi.org/10.3390/biom10060816] [PMID: 32466476]
[http://dx.doi.org/10.3390/ijms22137079] [PMID: 34209248]
[http://dx.doi.org/10.1021/jm901021k] [PMID: 19761212]
[http://dx.doi.org/10.1080/14756366.2019.1605364] [PMID: 31072147]
[http://dx.doi.org/10.3390/ijms21249623] [PMID: 33348757]
[http://dx.doi.org/10.5935/1984-6835.20120051]
[http://dx.doi.org/10.22270/ajprd.v7i6.616]
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[http://dx.doi.org/10.1039/b908937c] [PMID: 19830279]
[http://dx.doi.org/10.1111/j.1476-5381.1961.tb01080.x] [PMID: 19108149]
[http://dx.doi.org/10.1159/000158820] [PMID: 2242448]
[http://dx.doi.org/10.1016/j.ejmech.2016.10.052] [PMID: 27823888]
[http://dx.doi.org/10.1111/cbdd.13757] [PMID: 32657521]
[http://dx.doi.org/10.1182/blood.2020007651] [PMID: 33786587]
[http://dx.doi.org/10.1016/j.ejmech.2021.113472] [PMID: 33940463]