Abstract
Thiosemicarbazones (TSCNs) constitute a broad family of compounds (R1R2C=N-NH-C(S)- NR3R4), particularly attractive because many of them display some biological activity against a wide range of microorganisms and cancer cells. Their activity can be related to their electronic and structural properties, which offer a rich set of donor atoms for metal coordination and a high electronic delocalization providing different binding modes for biomolecules. Heterocycles such as pyrrole, imidazole and triazole are present in biological molecules such as Vitamine B12 and amino acids and could potentially target multiple biological processes. Considering this, we have explored the chemistry and biological properties of thiosemicarbazones series and their complexes bearing heterocycles such as pyrrole, imidazole, thiazole and triazole. We focus at the chemistry and cytotoxicity of those derivatives to find out the structure activity relationships, and particularly we analyzed those examples with the TSCN units in which the mechanism of action information has been profoundly studied and pathways determined, to promote future studies for heterocycle derivatives.
Keywords: Biological-activity, Coordination, Heterocycles, Metallodrugs, Structure-activity relationship, Thiosemicarbazones.
Graphical Abstract
[http://dx.doi.org/10.1016/j.ejmech.2019.03.024] [PMID: 30904782]
[http://dx.doi.org/10.1021/acs.chemrev.8b00396] [PMID: 30489072]
[http://dx.doi.org/10.1016/j.cct.2003.11.004]
[http://dx.doi.org/10.1021/acs.chemrev.8b00338] [PMID: 30507157]
[http://dx.doi.org/10.1021/cr3001252] [PMID: 23425067]
[http://dx.doi.org/10.1016/j.ccr.2008.07.004]
[http://dx.doi.org/10.1371/journal.pone.0188767] [PMID: 29652894]
[http://dx.doi.org/10.2174/1389557519666191029130310] [PMID: 31660812]
[http://dx.doi.org/10.3892/ol.2017.5995] [PMID: 28599449]
[http://dx.doi.org/10.1016/j.bmc.2006.06.013] [PMID: 16806947]
[http://dx.doi.org/10.1016/j.ejmech.2014.03.086] [PMID: 24727464]
[http://dx.doi.org/10.1002/zaac.201200012]
[http://dx.doi.org/10.1002/1521-3749(200110)627:10<2377:AID-ZAAC2377>3.0.CO;2-O]
[http://dx.doi.org/10.1021/ic051018j] [PMID: 16471964]
[http://dx.doi.org//10.1039/a908712e]
[http://dx.doi.org/10.1016/j.inoche.2006.12.024]
[http://dx.doi.org/10.1007/s12039-014-0699-4]
[http://dx.doi.org/10.1016/j.foodchem.2015.05.124] [PMID: 26213029]
[http://dx.doi.org/10.1016/j.jorganchem.2011.11.028]
[http://dx.doi.org/10.1039/c3ay40381e]
[http://dx.doi.org/10.1007/s002800050793] [PMID: 9654110]
[http://dx.doi.org/10.1128/AAC.04601-14] [PMID: 25712353]
[http://dx.doi.org/10.5455/musbed.20140101090010]
[http://dx.doi.org/10.3109/14756366.2012.688043] [PMID: 22651798]
[http://dx.doi.org/10.1134/S1070428019010135]
[http://dx.doi.org/10.1016/j.ica.2004.02.013]
[http://dx.doi.org/10.3390/ph13030037] [PMID: 32138202]
[http://dx.doi.org/10.1039/C8NJ04041A]
[http://dx.doi.org/10.1016/j.bmcl.2014.09.084] [PMID: 25451998]
[http://dx.doi.org/10.1021/acsomega.9b03778] [PMID: 32095716]
[http://dx.doi.org/10.14233/ajchem.2016.20127]
[http://dx.doi.org/10.1016/j.jinorgbio.2005.07.018] [PMID: 16188319]
[http://dx.doi.org/10.3390/molecules181012645] [PMID: 24129274]
[http://dx.doi.org/10.1016/j.molstruc.2018.11.025]
[http://dx.doi.org/10.4236/ojmc.2018.82004]
[http://dx.doi.org/10.1002/ardp.201900033] [PMID: 31475759]
[http://dx.doi.org/10.1016/B978-008044992-0.00510-1]
[http://dx.doi.org/10.1002/jhet.2565]
[http://dx.doi.org/10.1016/j.ica.2017.04.008]
[http://dx.doi.org/10.1590/S1984-82502016000200008]
[http://dx.doi.org/10.1016/j.poly.2017.06.024]
[http://dx.doi.org/10.1002/jhet.3253]
[http://dx.doi.org/10.1016/j.ejmech.2017.12.040] [PMID: 29329071]
[http://dx.doi.org/10.1021/acs.chemrestox.8b00204] [PMID: 30484632]
[http://dx.doi.org/10.1039/c3cs60386e] [PMID: 24492745]
[http://dx.doi.org/10.1016/j.ejmech.2014.11.033] [PMID: 25563511]
[http://dx.doi.org/10.1016/j.bmcl.2013.08.028] [PMID: 23988353]
[http://dx.doi.org/10.1186/s40360-018-0266-6] [PMID: 30522526]
[http://dx.doi.org/10.1016/j.ejmech.2018.04.003] [PMID: 29656201]
[http://dx.doi.org/10.1016/j.molstruc.2020.127951]
[http://dx.doi.org/10.1039/c2dt31199b] [PMID: 22955178]
[http://dx.doi.org/10.1002/cbic.201900545] [PMID: 31746118]
[http://dx.doi.org/10.1016/j.bmcl.2012.02.084] [PMID: 22444681]
[http://dx.doi.org/10.1021/acs.joc.5b00956] [PMID: 26332253]
[http://dx.doi.org/10.1016/j.jinorgbio.2019.110875] [PMID: 31706223]
[http://dx.doi.org/10.2174/1573406411666150514101026] [PMID: 25974080]
[http://dx.doi.org/10.1016/j.jinorgbio.2018.02.014] [PMID: 29510336]
[http://dx.doi.org/10.1039/C5RA04498G]
[http://dx.doi.org/10.1016/j.ejmech.2017.12.024] [PMID: 29287249]
[http://dx.doi.org/10.1002/aoc.3813]
[http://dx.doi.org/10.1021/jm049147h] [PMID: 15828843]
[http://dx.doi.org/10.1111/j.1749-6632.1965.tb12545.x] [PMID: 5323377]
[http://dx.doi.org/10.1186/1743-422X-5-64] [PMID: 18498627]
[http://dx.doi.org/10.1021/jm2006047] [PMID: 21721528]
[http://dx.doi.org/10.1021/jm900528d] [PMID: 19637923]
[http://dx.doi.org/10.1016/j.ica.2019.04.019]
[http://dx.doi.org/10.1016/j.molstruc.2019.126904]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.09.084] [PMID: 30227206]