RARE-EARTH SALTS AS EMERGING ANTI-INFECTIVE PLATFORMS: ANTIMICROBIAL AND ANTILEISHMANIAL ACTIVITY OF GADOLINIUM, NEODYMIUM, AND SAMARIUM COMPOUNDS

Rare-earth-based compounds have attracted increasing interest as bioactive inorganic platforms due to their distinctive coordination chemistry and potential interactions with microbial and parasitic targets. This study evaluated the preliminary antimicrobial, antileishmanial, and cytotoxic profiles of three rare-earth compounds: D1 (samarium oxide), D2 (gadolinium carbonate), and D3 (neodymium). Antimicrobial activity was assessed by the agar well diffusion method against methicillin-resistant Staphylococcus aureus ATCC 33591, Enterococcus faecalis ATCC 29212, and Candida albicans SC5314 at 4000 µg/mL, using cefoxitin, vancomycin, and amphotericin B as positive controls. Antileishmanial activity was evaluated against promastigotes of Leishmania amazonensis IFLA/BR/1967/PH8 using the resazurin reduction assay after 24 h of exposure to 62.25–1000 µg/mL of D1–D3. Cytotoxicity was assessed in RAW 264.7 macrophages over the same concentration range, and selectivity indices (SI) were calculated as CC₅₀/IC₅₀. All compounds produced measurable inhibition zones, with greater activity against Gram-positive bacteria than C. albicans. D3 showed the largest zones against MRSA, E. faecalis, and C. albicans (21.1 ± 0.742, 24.8 ± 1.643, and 11.7 ± 0.671 mm, respectively), followed by D2 and D1. D3 was also the most active compound against L. amazonensis, with an IC₅₀ of 85.28 µg/mL, followed by D2 (121.1 µg/mL) and D1 (228.9 µg/mL), whereas amphotericin B showed substantially greater potency (IC₅₀ = 0.4466 µg/mL). In RAW 264.7 macrophages, CC₅₀ values were 248.3, 248.0, and 189.0 µg/mL for D1, D2, and D3, respectively, compared with 3.585 µg/mL for amphotericin B. SI values were 1.08, 2.05, 2.22, and 8.03, respectively. Overall, the compounds demonstrated preliminary in vitro antimicrobial and antileishmanial activity, with D3 showing the most favorable profile. However, their modest selectivity indices and the use of promastigotes highlight the need for further evaluation, including MIC, MBC, MFC, intracellular amastigote assays, physicochemical characterization, mechanism-of-action studies, and formulation strategies.

This work was supported by the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) (E-26/200.815/2021; E-26/010.000981/2019; E-26/010.002362/2019; E-26/211.269/2021; E-26/211.207/2021) and the National Council for Scientific and Technological Development (CNPq) (301069/2018-2; 304774/2021-9; 401692/2023-0; 440852/2023-4; 444089/2023).