Search

A series of new metal complexes, [Cu(ITZ) 2 Cl 2 ] ⋅ 5H 2 O (1) , [Cu(NO 3 ) 2 (ITZ) 2 ] ⋅ 3H 2 O ⋅ C 4 H 10 O (2) and [Cu(ITZ) 2 )(PPh 3 ) 2 ]NO 3  ⋅ 5H 2 O (3) were synthesized by a reaction of itraconazole (ITZ) with the respective copper salts under reflux. The metal complexes were characterized by elemental analyses, molar conductivity, 1 H and 13 C{ 1 H} nuclear magnetic resonance, UV-Vis, infrared and EPR spectroscopies. The antifungal activity of these metal complexes was evaluated against the main sporotrichosis agents: Sporothrix brasiliensis, Sporothrix schenkii, and Sporothrix globosa. All three new compounds inhibited the growth of S. brasiliensis and S. schenckii at lower concentrations than the free azole, with complex 2 able to kill all species at 4 μM and induce more pronounced alterations in fungal cells. Complexes 2 and 3 exhibited higher selectivity and no mutagenic effect at the concentration that inhibited fungal growth and affected fungal cells. The strategy of coordinating itraconazole (ITZ) to copper was successful, since the corresponding metal complexes were more effective than the parent drug. Particularly, the promising antifungal activity of the Cu-ITZ complexes makes them potential candidates for the development of an alternative drug to treat mycoses., (© 2024 Wiley-VCH GmbH.)

Currently the only drug available to treat Chagas disease in Brazil is benznidazole (BZN). Therefore, there is an urgent need to discover and develop new anti- Trypanosoma cruzi candidates. In our continuous effort to enhance clinical antiparasitic drugs using synergistic strategy, BZN was coordinated to silver and copper ions to enhance its effectiveness to treat that illness. In this work, the syntheses of four novel metal-BZN complexes, [Ag(BZN) 2 ]NO 3 ·H 2 O (1), [CuCl 2 (BZN)(H 2 O)]·1/2CH 3 CN (2), [Ag(PPh 3 ) 2 (BZN) 2 ]NO 3 ·H 2 O (3), and [Cu(PPh 3 ) 2 (BNZ) 2 ]NO 3 ·2H 2 O (4), and their characterization using multiple analytical and spectroscopic techniques such as Infrared (FTIR), Nuclear Magnetic Resonance ( 1 H, 13 C, 31 P), UV-Visible (UV-Vis), Electron Paramagnetic Resonance (EPR), conductivity and elemental analysis are described. IC 50 (Half-maximal inhibitory concentration) values of Ag-BZN compounds are about five to ten times lower than benznidazole itself in both proliferation stages of the parasite (epimastigotes and amastigotes). The cytotoxicity of both compounds in human cells (fibroblasts and hepatocytes) are comparable to BZN, indicating that Ag-BZN complexes can be more selective than BZN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A series of new transition metal coordination polymers, [Zn(Ac) 2 (FLZ) 2 ] n (1) , [Zn(FLZ) 2 (Cl) 2 ] n (2), {[Zn(FLZ) 2 ](NO 3 ) 2 } n (3), [Cu(FLZ) 2 (CH₃COO) 4 ] n (4) , {[Cu(FLZ) 2 Cl 2 ]} n (5) and {[Cu(FLZ) 2 ](NO 3 ) 2 } n (6), were synthesized by the reaction of fluconazole (FLZ) with the respective zinc or copper salts under mild conditions. The molecular structure of these compounds was elucidated by several analytical and spectroscopy techniques such as elemental analyses, 1 H and 13 C{ 1 H} nuclear magnetic resonance, electronic paramagnetic resonance, and infrared spectroscopy. Single-crystal X-ray diffraction confirmed the structure of the compounds 2, 4, 5 and 6 in solid state. The antichagasic activity of these compounds was evaluated against different forms of Trypanosoma cruzi. Compound 2 exhibited the highest activity against intracellular amastigotes. The ultrastructural changes in epimastigotes and intracellular amastigotes were investigated. These promising biological results demonstrated that the zinc or copper coordination polymers can form very active anti-parasitic compounds. The resulting compounds are more effective than the free azole drug and, consequently, great candidates for the treatment of Chagas disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although there are various treatment options for cancer, this disease still has caused an increasing number of deaths, demanding more efficient, selective and less harmful drugs. Several classes of ruthenium compounds have been investigated as metallodrugs for cancer, mainly after the entry of imidazolH [ trans -RuCl 4 -(DMSO-S)(imidazole)] (NAMI-A) and indazolH [ trans -RuCl 4 -(Indazol) 2 ] (KP1019) in clinical trials. In this sense, Ru II complexes with general formula [Ru(L1-3)(bipy) 2 ]PF 6 (1-3) (L1 = ethyl 3-(6-methyl-2-oxo-2 H -chromen-3-yl)-3-oxopropanoate, L2 = ethyl 3-(7-(diethylamino)-2-oxo-2 H -chromen-3-yl)-3-oxopropanoate, L3 = ethyl 3-(8-methoxy-2-oxo-2 H -chromen-3-yl)-3-oxopropanoate and bipy = bipyridine) have been synthesized. The crystal structure of 2 revealed that the Ru II atom lies on a distorted octahedral geometry with the deprotonated ligand (L2 - ) coordinated through β-ketoester group oxygen atoms. In vitro cytotoxic activity of the compounds was evaluated against 4T1 (murine mammary carcinoma) and B16-F10 (murine metastatic melanoma) tumor cells, and the non-tumor cell line BHK-21 (baby hamster kidney). Coordination with Ru II resulted in expressive enhancement of cytotoxic activity. The precursors were inactive below 100 μM and the final Ru II complexes (1-3) showed IC 50 ranging from 2.0 to 12.8 μM; 2 being the most potent compound. DNA interaction studies revealed a greater capacity of the complexes to interact with DNA than the ligands, where, 2 exhibited the highest K b constant of 2.2 × 10 4 M -1 . Fluorescence investigation demonstrated that 1-3 are capable of quenching the fluorescence emission of the EtdBr-DNA complex up to 40%. Molecular docking showed that the interaction of 1-3 between the DNA base pairs from the coumarin portion was with scores of 67.28, 68.62 and 64.88, respectively, and 75.45 for ellipticine, suggesting an intercalative mode of binding. Our findings show that the Ru II complexes are eligible for continuing to be investigated as potential antitumor compounds.

A series of new metal complexes, [Zn(KTZ) 2 (Ac) 2 ]·H 2 O (1) , [Zn(KTZ) 2 Cl 2 ]·0.4CH 3 OH (2), [Zn(KTZ) 2 (H 2 O)(NO 3 )](NO 3 ) (3), [Cu(KTZ) 2 (Ac) 2 ]·H 2 O (4) , [Cu(KTZ) 2 Cl 2 ]·3.2H 2 O (5), [Cu(KTZ) 2 (H 2 O)(NO 3 )](NO 3 )·H 2 O (6), were synthesized by a reaction of ketoconazole (KTZ) with their respective zinc or copper salts under mild conditions. Similarly, six corresponding metal-CTZ (clotrimazole) complexes [Zn(CTZ) 2 (Ac) 2 ]·4H 2 O (7) , [Zn(CTZ) 2 Cl 2 ] (8), [Zn(CTZ) 2 (H 2 O)(NO 3 )](NO 3 )·4H 2 O (9), [Cu(CTZ) 2 (Ac) 2 ]·H 2 O (10) , [Cu(CTZ) 2 Cl 2 ]·2H 2 O (11), [Cu(CTZ) 2 (H 2 O)(NO 3 )](NO 3 )·2H 2 O (12), were obtained. These metal complexes were characterized by elemental analyses, molar conductivity, 1 H and 13 C{ 1 H} nuclear magnetic resonance, UV/Vis, and infrared spectroscopies. Further, the crystal structure for complexes 7 and 10 was determined by single-crystal X-ray diffraction. The antifungal activity of these metal complexes was evaluated against three fungal species of medical relevance: Candida albicans, Cryptococcus neoformans, and Sporothrix brasiliensis. Complexes 1 and 3 exhibited the greatest antifungal activity with a broad spectrum of action at low concentrations and high selectivity. Some morphological changes induced by these metal complexes in S. brasiliensis cells included yeast-hyphae conversion, an increase in cell size and cell wall damage. The strategy of coordination of clinic drugs (KTZ and CTZ) to zinc and copper was successful, since the corresponding metal complexes were more effective than the parent drug. Particularly, the promising antifungal activities displayed by Zn-KTZ complexes make them potential candidates for the development of an alternative drug to treat mycoses., (Copyright © 2021 Elsevier Inc. All rights reserved.)