Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 503, P. 215608 - 215608

Published: Jan. 2, 2024

Language: Английский

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Facing diseases caused by trypanosomatid parasites: rational design of multifunctional oxidovanadium(IV) complexes with bioactive ligands

Frontiers in Chemical Biology, Journal Year: 2024, Volume and Issue: 2

Published: Jan. 16, 2024

Searching for new prospective drugs against Chagas disease (American trypanosomiasis) and Leishmaniasis, a series of five heteroleptic vanadium compounds, [V IV O(L-H)(mpo)], where L are 8-hydroxyquinoline derivatives mpo is 2-mercaptopyridine N -oxide, synthesized characterized. Comprehensive characterizations conducted in solid state solution. The compounds evaluated on epimastigotes trypomastigotes Trypanosoma cruzi promastigotes Leishmania infantum , alongside VERO cells, as mammalian cell model. exhibit activity both forms T. L. with the trypomastigote infective stage displaying highest sensitivity. most selective compound O(L2-H)(mpo)], L2 = 5-chloro-7-iodo-8-hydroxyquinoline, globally shows adequate selectivity towards parasite was selected to carry out further in-depth biological studies. O(L2-H)(mpo)] significantly impacted infection potential cell-derived hindered replication amastigote form. Low total uptake by parasites preferential accumulation soluble proteins fraction, negligible localization DNA determined. A trypanocide effect observed across various concentrations compound. generation oxidative stress induction mitochondria-dependent apoptosis proposed main mechanisms parasite’s death V O compounds. Both theoretical predictions experimental data support hypothesis that inhibiting parasite-specific enzyme NADH-fumarate reductase plays crucial role trypanocidal action these complexes. Globally, O(L-H)(mpo)] complexes could be considered interesting anti- agents deserve research.

Language: Английский

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Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

Antibiotics, Journal Year: 2023, Volume and Issue: 12(3), P. 619 - 619

Published: March 20, 2023

In the context of global health issue caused by growing occurrence antimicrobial resistance (AMR), need for novel agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source antibiotics. Here, we report computer-aided drug design (CADD) based on 'scaffold-hopping' approach synthesis antibacterial evaluation fac-Re(I) tricarbonyl bearing clotrimazole (ctz) as monodentate ligand. The prepared molecules were selected following pre-screening in silico analysis according to modification 2,2'-bipyridine (bpy) ligand coordination sphere complexes. CADD pointed chiral 4,5-pinene 5,6-pinene bipyridine derivatives most promising candidates. corresponding synthesized, tested toward methicillin-sensitive -resistant S. aureus strains, obtained results evaluated with regard their binding affinity homology model MurG enzyme. Overall, title species revealed very similar minimum inhibitory concentration (MIC) bactericidal (MBC) values those reference compound used scaffold our approach. docking scores advocate viability de novo design, potential strategy more cost- time-efficient discovery new

Language: Английский

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New insights on transition metal coordination compounds with biological active azole and nitroimidazole derivatives

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 494, P. 215360 - 215360

Published: Aug. 1, 2023

Language: Английский

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Multifunctional Organometallic Compounds Active against Infective Trypanosomes: Ru(II) Ferrocenyl Derivatives with Two Different Bioactive Ligands

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(25), P. 11667 - 11687

Published: June 11, 2024

Human African trypanosomiasis (HAT, sleeping sickness) and American (Chagas disease) are endemic zoonotic diseases caused by genomically related trypanosomatid protozoan parasites (Trypanosoma brucei Trypanosoma cruzi, respectively). Just a few old drugs available for their treatment, with most of them sharing poor safety, efficacy, pharmacokinetic profiles. Only fexinidazole has been recently incorporated into the arsenal treatment HAT. In this work, new multifunctional Ru(II) ferrocenyl compounds were rationally designed as potential agents against these pathogens including in single molecule 1,1′-bis(diphenylphosphino)ferrocene (dppf) two bioactive bidentate ligands: pyridine-2-thiolato-1-oxide ligand (mpo) polypyridyl ligands (NN). Three [Ru(mpo)(dppf)(NN)](PF6) derivatives chloride counterion synthesized fully characterized solid state solution. They showed vitro activity on bloodstream T. (EC50 = 31–160 nM) cruzi trypomastigotes 190–410 nM). Compounds lowest EC50 values when compared to whole set metal-based previously developed us. addition, several Ru good selectivity toward parasites, particularly highly proliferative form brucei. Interaction DNA generation reactive oxygen species (ROS) ruled out targets modes action compounds. Biochemical assays silico analysis led insight that they able inhibit NADH-dependent fumarate reductase from cruzi. One representative hit induced mild oxidation low molecular weight thiols The stable at least 72 h different media more lipophilic than both ligands, mpo NN. An initial assessment therapeutic efficacy one potent selective candidates, [Ru(mpo)(dppf)(bipy)]Cl, was performed using murine infection model acute trypanosomiasis. This compound lacks toxicity applied animals dose/regimen described, but unable control parasite proliferation vivo, probably because its rapid clearance or biodistribution extracellular fluids. Future studies should investigate pharmacokinetics vivo involve further research gain deeper mechanism

Language: Английский

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Metallomics: An Essential Tool for the Study of Potential Antiparasitic Metallodrugs

ACS Omega, Journal Year: 2024, Volume and Issue: 9(14), P. 15744 - 15752

Published: March 25, 2024

Metallomics is an emerging area of omics approaches that has grown enormously in the past few years. It integrates research related to metals biological systems, symbiosis with genomics and proteomics. These can provide in-depth insights into mechanisms action potential metallodrugs, including their physiological metabolism molecular targets. Herein, we review most significant advances concerning cellular uptake subcellular distribution assays different metallodrugs activity against Trypanosma cruzi, protozoan parasite causes Chagas disease, a pressing health problem high-poverty areas Latin America. Furthermore, first multiomics metallomics, proteomics, transcriptomics for comprehensive study anti-Trypanosoma cruzi are described.

Language: Английский

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Facile synthesis, characterization, molecular and dynamic optical properties of metronidazole and sulfamethoxazole adducts of tricarbonyl(1-5-η-2-methoxycyclohexadienylium)iron

Discover Chemistry., Journal Year: 2025, Volume and Issue: 2(1)

Published: April 28, 2025

Language: Английский

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Tricarbonyl rhenium(i) complexes with 8-hydroxyquinolines: structural, chemical, antibacterial, and anticancer characteristics

RSC Advances, Journal Year: 2024, Volume and Issue: 14(25), P. 18080 - 18092

Published: Jan. 1, 2024

Twelve tricarbonyl Re( i ) complexes with bidentate 8-hydroxyquinolinato and monodentate diazole ligands were synthesized, characterized by scXRD, IR, NMR, UV-Vis methods, checked for antibacterial anticancer activity.

Language: Английский

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Resurgence and Repurposing of Antifungal Azoles by Transition Metal Coordination for Drug Discovery

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(10), P. 2398 - 2398

Published: Sept. 28, 2023

Coordination compounds featuring one or more antifungal azole (AA) ligands constitute an interesting family of candidate molecules, given their medicinal polyvalence and the viability drug complexation as a strategy to improve repurpose available medications. This review reports work performed in field coordination derivatives AAs synthesized for medical purposes by discussing corresponding publications emphasizing most promising discovered so far. The resulting overview highlights efficiency metallic species, well potential still lying this research area.

Language: Английский

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Synthesis, structural characterization and antitrypanosomal activity of ferrocenyl-based imines with (2 or 4)-nitrophenyl-2-furan group

Inorganic Chemistry Communications, Journal Year: 2024, Volume and Issue: 167, P. 112714 - 112714

Published: June 10, 2024

Language: Английский

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