Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

Abstract

Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in μg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.

Anticancer and antileishmanial in vitro activity of gold(I) complexes with 1,3,4‐oxadiazole‐2(3H)‐thione ligands derived from δ‐D‐gluconolactone

“…In the case of skin melanoma‐derived cell line B16‐F10, results show that complexes 9 and 10 (triethylphosphine derivatives) are more cytotoxic and selective than the triphenylphosphine analogue compounds 11 and 12 , presenting IC 50 values of 2.0 ± 0.2 and 3.2 ± 0.2 μ m , with selectivity indexes of 10.6 and 6.9, respectively. Similar evidence was previously found in the literature, where triethylphosphine derivatives have shown better activity, possibly because of steric factors, a result that is consistent with past works of other leading authors (Chaves et al., 2014, 2015, 2016; de Almeida et al., 2017; Garcia et al., 2016). Furthermore, in the case of skin melanoma (B16‐F10), if we compare the results for compounds 9 and 10 , we see that compound 9 is slightly more active than compound 10 (with IC 50 of 2 ± 0.2, µ m compared to 3.2 ± 0.2 µ m from compound 10 ).…”

“…The significance of this work lies in the design and synthesis of novel ligands using multiple biologically active groups in order to enhance the overall effectivity and selectivity of the gold(I) complexes. Our research group already reported several studies describing gold(I) complexes with different ligands based on different substrates, such as benzyl and benzoyl chloride (Chaves et al., 2014), alcohols and fatty acids (de Almeida et al., 2017), some monosaccharides (Chaves et al., 2015), and adamantane (Garcia et al., 2016); all of them showed selective cytotoxicity against tumor‐derived cell lines and were more effective than cisplatin. Some of these compounds also presented antileishmanial activity against Leishmania infantum and Leishmania braziliensis intracellular amastigotes and axenic promastigotes (Chaves et al., 2016).…”

Gold Drugs with {Au(PPh3)}+ Moiety: Advantages and Medicinal Applications

“…Complexes 49 and 50 among others (Figure 8), with ligands derived from carbohydrates, were also evaluated for their antitubercular activity. [66] Interestingly, 49 was more active than the analogous {Au(PEt 3 )} + complex, but the opposite was found for complex 50 and its {Au(PEt 3 )} + derivative. 49 was the most active in all of the Au compounds studied in this report (MIC 90 = 2.50 μg/mL) including the [ClÀ Au(PPh 3 )] parent compound (MIC 90 = 25.00 μg/mL).…”

“…Both 48 and the analogous {Au(PEt 3 )} + complex were tested (IC 90 =1.204 and 1.050 μM) and while the {Au(PEt 3 )} + complex was slightly more active, 48 was more selective towards M. tuberculosis than Vero cells (SI=7.310 and 4.983 respectively). Complexes 49 and 50 among others (Figure 8), with ligands derived from carbohydrates, were also evaluated for their antitubercular activity [66] . Interestingly, 49 was more active than the analogous {Au(PEt 3 )} + complex, but the opposite was found for complex 50 and its {Au(PEt 3 )} + derivative.…”

An ion-imprinted thiocyanato-functionalized mesoporous silica for preconcentration of gold(III) prior to its quantitation by slurry sampling graphite furnace AAS

“…The numerous applications of gold, which is classified as a toxic element, necessitate the development of reliable and precise analytical procedures for its determination in various environmental samples [1].…”