Explore the vast range of titles available.

Background. Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. Aims. In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)3(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. Methods. The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. Results. Three of the Mn complexes investigated (4–6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. Conclusions. Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future.

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.

The first examples of Ru(II) η6‐arene (benzene and p‐cymene) complexes containing a bidentate triazolylidene‐triazolide ligand have been prepared and fully characterized. Their antiproliferative effect has been investigated against tumour cells A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116dox (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The Ru complex bearing the p‐cymene arene group exhibited a stronger antiproliferative effect across all tested cell lines, while the benzene‐containing complex displayed higher selectivity toward tumor cells. Both complexes induced apoptosis, likely through ROS production (in the benzene complex), and inhibited tumorigenic processes, including cell migration and angiogenesis. In zebrafish models, they showed strong selectivity for cancer cells with minimal toxicity to healthy cells, effectively reducing the proliferation of HCT116 colorectal cancer cells. This study provides the first in vivo evidence of the anticancer potential of Ru triazolylidenes in zebrafish models. The anticancer potential of Ru(II) complexes with bidentate triazolylidene‐triazolide ligands has been demonstrated against A2780 (ovarian carcinoma), and HCT116 (colorectal carcinoma) tumor cell lines. The work provides an in‐depth evaluation of these complexes, examining their in vitro antiproliferative activity, mechanisms of inducing cell death, cell migration, anti‐angiogenic effects, and therapeutic performance in vivo zebrafish xenograft models.

The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2Ru1 and [Ru(bipy)22(μ-C12H8N6-N,N)][CF3SO3]4Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L−1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.

Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η6-arene)Ru(L)Cl][X] X = CF3SO3 (JHOR10) and PF6 (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.

Mexico is one of the three areas of the world with the greatest terrestrial and cultural biological diversity. The diversity of Mexican medicinal flora has been studied for a long time and several bioactive compounds have been isolated. The investigation of marine resources, and particularly the potential of Mexican marine resources, has not been intensively investigated, even though the Yucatan Peninsula occupies 17.4% of the total of the Mexican coast, with great biological diversity in its coasts and the ocean. There are very few studies on the chemistry of natural products from marine organisms that were collected along the coasts of the Yucatan Peninsula and most of them are limited to the evaluation of the biological activity of their organic extracts. The investigations carried out on marine species from the Yucatan Peninsula resulted in the identification of a wide structural variety of natural products that include polyketides, terpenoids, nitrogen compounds, and biopolymers with cytotoxic, antibacterial, antifouling, and neurotoxic activities. This review describes the literature of bioprospecting and the exploration of the natural product diversity of marine organisms from the coasts of the Yucatan Peninsula up to mid-2019.

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).Graphical abstract

Invasive fungal infections, especially those caused by Candida spp., have been classified as a serious global threat. The emergence of species intrinsically resistant to current drugs, along with the increase in acquired resistance, places significant pressure on the need to develop novel and more effective antifungal agents. A limited number of studies have shown the potential of palladium organometallic complexes as promising antifungal alternatives. Although the mechanism of antifungal activity of these complexes remains unaddressed, the findings support the idea that designing palladium (II) complexes could represent the next generation of antifungals. In this work, we synthesized four cyclopalladated complexes, 1a , 1b , 2a , and 2b, from Schiff base–amine phosphanes and evaluated their antifungal potential. Specifically, we assessed their spectrum of activity against several medically relevant Candida spp., their capacity to overcome resistance to current antifungal drugs, antibiofilm properties, uptake by fungal cells, in vivo toxicity, and intracellular effects. The most promising complexes, 1b and 2b , induce strong oxidative stress and lipid peroxidation, inhibit lipolysis, and disrupt vacuole integrity. Moreover, the rational design of the complexes allowed us to infer important structure–activity relationships. Our findings highlight the potential of palladium complexes as promising scaffolds for future antifungal therapeutic strategies and open new horizons for further development.

Multidrug-resistant (MDR) Klebsiella pneumoniae, classified by the World Health Organization (WHO) as a critical priority pathogen, represents a global health thereat requiring novel antimicrobials urgently. Here we evaluated the in vitro antimicrobial activity of a novel iridium-based compound (OMKP-3), against MDR K. pneumoniae. OMKP-3 exhibited robust antimicrobial activity in M9 minimal media (MIC=6.25μg/mL) and rapid bactericidal effect (MBC=12.5μg/mL) against the tested MDR K. pneumoniae strains. OMKP-3 showed antibiofilm ability and was active against multiple MDR Gram-negative pathogens, including Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa and Serratia marcescens (MIC range:6.25-25μg/mL). Importantly, OMKP-3 showed no cytotoxicity against mammalian cells after 24 hours of exposure. When combined with polymyxin B, OMKP-3 acted as an adjuvant, enhancing polymyxin B activity (FIC≤0.5). OMKP-3 was less prone to induce high-level resistance in MDR K. pneumoniae compared to ciprofloxacin, and supressed the growth of resistant bacteria at a low and non-cytotoxic concentration (4xMIC). K. pneumoniae strains harboring truncated Ompk35/36 porin genes exhibited higher OMKP-3 MICs, indicating that these porins may serve as an important entry pathway. Spectrometry analysis revealed that OMKP-3 was able to accumulate intracellularly (1.57μg/mL), with minimal Resistance-Nodulation-Division (RND) efflux pump extrusion involvement. Furthermore, analysis of the resistant mutant, harboring a mutation in the outer membrane protein DegS, together with fluorescence microscopy, suggests that OMKP-3 induces membrane-associated damage. No cross-resistance between OMKP-3 and commonly used antibiotics was observed. Collectively, these findings identify OMKP-3 as a promising novel antimicrobial agent against MDR K. pneumoniae, likely acting through an unexplored bacterial target.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredOeiras Municipality and ITQB-NOVA, Innovalley Proof-of-concept award 2nd and 3rd EditionsFCT - Fundação para a Ciência e a Tecnologia, I.P. (MOSTMICRO-ITQB R&D Unit), UID/PRR/4612/2025LS4FUTURE Associated Laboratory, DOI 10.54499/LA/P/0087/2020