Pristine Photopolymerizable Gelatin Hydrogels: A Low-Cost and Easily Modifiable Platform for Biomedical Applications.

The study addresses the challenge of temperature sensitivity in pristine gelatin hydrogels, widely used in biomedical applications due to their biocompatibility, low cost, and cell adhesion properties. Traditional gelatin hydrogels dissolve at physiological temperatures, limiting their utility. Here, we introduce a novel method for creating stable hydrogels at 37 °C using pristine gelatin through photopolymerization without requiring chemical modifications. This approach enhances consistency and simplifies production and functionalization of the gelatin with bioactive molecules. The stabilization mechanism involves the partial retention of the triple-helix structure of gelatin below 25 °C, which provides specific crosslinking sites. Upon activation by visible light, ruthenium (Ru) acts as a photosensitizer that generates sulphate radicals from sodium persulphate (SPS), inducing covalent bonding between tyrosine residues and "locking" the triple-helix conformation. The primary focus of this work is the characterization of the mechanical properties, swelling ratio, and biocompatibility of the photopolymerized gelatin hydrogels. Notably, these hydrogels supported better cell viability and elongation in normal human dermal fibroblasts (NHDFs) compared to GelMA, and similar performance was observed for human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). As a proof of concept for functionalization, gelatin was modified with selenous acid (GelSe), which demonstrated antioxidant and antimicrobial capacities, particularly against E. coli and S. aureus. These results suggest that pristine gelatin hydrogels, enhanced through this new photopolymerization method and functionalized with bioactive molecules, hold potential for advancing regenerative medicine and tissue engineering by providing robust, biocompatible scaffolds for cell culture and therapeutic applications.

Following the Trace of Cyclodextrins on the Selenium and Tellurium Odyssey.

There is an urgent need to develop safer and more effective modalities for the treatment of numerous pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Over the past decades, cyclodextrins (CDs) have gathered great attention as potential drug carriers due to their ability to enhance their bioactivities and properties. Likewise, selenium (Se) and tellurium (Te) have been extensively studied during the last decades due to their possible therapeutical applications. Although there is limited research on the relationship between Se and Te and CDs, herein, we highlight different representative examples of the advances related to this topic as well as give our view on the future directions of this emerging area of research. This review encompasses three different aspects of this relationship: (1) modification of the structure of the different CDs; (2) formation of host-guest interaction complexes of naïve CDs with Se and Te derivatives in order to overcome specific limitations of the latter; and (3) the use of CDs as catalysts to achieve novel Se and Te compounds.

Selenization of Small Molecule Drugs: A New Player on the Board.

There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research.

Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties.

Cancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they are not always effective or safe, often failing to achieve the desired results. This is why it is necessary to continue the search for new therapies. One of the strategies for obtaining new antitumor drugs is the use of 1,4-naphthoquinone as a scaffold in synthetic or natural products with antitumor activity. This review focuses on compiling studies related to the antitumor activity of 1,4-naphthoquinone and its natural and synthetic derivatives over the last 10 years. The work describes the main natural naphthoquinones with antitumor activity and classifies the synthetic naphthoquinones based on the structural modifications made to the scaffold. Additionally, the formation of metal complexes using naphthoquinones as a ligand is considered. After a thorough review, 197 synthetic compounds with potent biological activity against cancer have been classified according to their chemical structures and their mechanisms of action have been described.

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas.

Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC50 values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer.

Formulation Studies with Cyclodextrins for Novel Selenium NSAID Derivatives.

Commercial cyclodextrins (CDs) are commonly used to form inclusion complexes (ICs) with different molecules in order to enhance their water solubility, stability, and bioavailability. Nowadays, there is strong, convincing evidence of the anticancer effect of selenium (Se)-containing compounds. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their further evaluation and clinical use. In this work, we study the enhancement of solubility with CD complexes for a set of different nonsteroidal anti-inflammatory drug (NSAID) derivatives with Se as selenoester or diacyl diselenide chemical forms, with demonstrated antitumoral activity. The CD complexes were analyzed via nuclear magnetic resonance (NMR) spectroscopic techniques. In order to obtain additional data that could help explain the experimental results obtained, 3D models of the theoretical CD-compound complexes were constructed using molecular modeling techniques. Among all the compounds, I.3e and II.5 showed a remarkable increase in their water solubility, which could be ascribed to the formation of the most stable interactions with the CDs used, in agreement with the in silico studies performed. Thus, the preliminary results obtained in this work led us to confirm the selection of ß and γ-CD as the most suitable for overcoming the pharmaceutical drawbacks of these Se derivatives.

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability. The development of biomaterials with antioxidant capacity is poised to overcome this roadblock. Moreover, in the treatment of chronic inflammation, material-based strategies would allow the controlled and targeted release of antioxidants into the affected tissue. In this review, we revise the main causes and effects of oxidative stress, and survey antioxidant biomaterials used for the treatment of chronic wounds, neurodegenerative diseases, cardiovascular diseases (focusing on cardiac infarction, myocardial ischemia-reperfusion injury and atherosclerosis) and osteoporosis. We anticipate that these developments will lead to the emergence of new technologies for tissue engineering, control of oxidative stress and prevention of diseases associated with oxidative stress.

Novel Pitolisant-Derived Sulfonyl Compounds for Alzheimer Disease.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder characterized by cognitive decline, memory loss, behavioral changes, and other neurological symptoms. Considering the urgent need for new AD therapeutics, in the present study we designed, synthesized, and evaluated multitarget compounds structurally inspired by sulfonylureas and pitolisant with the aim of obtaining multitarget ligands for AD treatment. Due to the diversity of chemical scaffolds, a novel strategy has been adopted by merging into one structure moieties displaying H3R antagonism and acetylcholinesterase inhibition. Eight compounds, selected by their binding activity on H3R, showed a moderate ability to inhibit acetylcholinesterase activity in vitro, and two of the compounds (derivatives 2 and 7) were also capable of increasing acetylcholine release in vitro. Among the tested compounds, derivative 2 was identified and selected for further in vivo studies. Compound 2 was able to reverse scopolamine-induced cognitive deficits with results comparable to those of galantamine, a drug used in clinics for treating AD. In addition to its efficacy, this compound showed moderate BBB permeation in vitro. Altogether, these results point out that the fragment-like character of compound 2 leads to an optimal starting point for a plausible medicinal chemistry approach for this novel strategy.

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation.

The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay. The new Se-NSAID derivatives bearing this unique combination showed antioxidant activity in a time- and dose-dependent manner, and also displayed different antiproliferative profiles in a panel of eight cancer cell lines as determined by the MTT assay. Ibuprofen derivative 5 was not only the most antioxidant agent, but also selectively induced toxicity in all the cancer cell lines tested (IC50 < 10 µM) while sparing nonmalignant cells, and induced apoptosis partially without enhancing the caspase 3/7 activity. Furthermore, NSAID derivative 5 significantly suppressed tumor growth in a subcutaneous colon cancer xenograft mouse model (10 mg/kg, TGI = 72%, and T/C = 38%) without exhibiting any apparent toxicity. To our knowledge, this work constitutes the first report on in vitro and in vivo anticancer activity of an unprecedented Se-NSAID hybrid derivative and its rational use for developing precursors for bioisosteric selenocompounds with appealing therapeutic applications.

Exploring Novel Drug Combinations: The Therapeutic Potential of Selanyl Derivatives for Leishmania Treatment.

This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of Leishmania major (L. major) and Leishmania infantum (L. infantum). The L. infantum strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives (A4, A5, A6 and A8) presented IC50 values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The A4-A6 and A8 derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds A6 and A8 presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds A6 and A8 present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism.

Preparation of Selenium-Based Drug-Modified Polymeric Ligand-Functionalised Fe3O4 Nanoparticles as Multimodal Drug Carrier and Magnetic Hyperthermia Inductor.

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

Novel Acylselenourea Derivatives: Dual Molecules with Anticancer and Radical Scavenging Activity.

Oxidative stress surrounding cancer cells provides them with certain growth and survival advantages necessary for disease progression. In this context, Se-containing molecules have gained attention due to their anticancer and antioxidant activity. In our previous work, we synthesized a library of 39 selenoesters containing functional groups commonly present in natural products (NP), which showed potent anticancer activity, but did not demonstrate high radical scavenger activity. Thus, 20 novel Se derivatives resembling NP have been synthesized presenting acylselenourea functionality in their structures. Radical scavenger activity was tested using DPPH assay and in vitro protective effects against ROS-induced cell death caused by H2O2. Additionally, antiproliferative activity was evaluated in prostate, colon, lung, and breast cancer cell lines, along with their ability to induce apoptosis. Compounds 1.I and 5.I showed potent cytotoxicity against the tested cancer cell lines, along with high selectivity indexes and induction of caspase-mediated apoptosis. These compounds exhibited potent and concentration-dependent radical scavenging activity achieving DPPH inhibition similar to ascorbic acid and trolox. To conclude, we have demonstrated that the introduction of Se in the form of acylselenourea into small molecules provides strong radical scavengers in vitro and antiproliferative activity, which may lead to the development of promising dual compounds.

Next generation of selenocyanate and diselenides with upgraded leishmanicidal activity.

Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.

Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors.

In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a-19a and 1b-19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment.

Since the beginning of history, natural products have been an abundant source of bioactive molecules for the treatment of different diseases, including cancer. Many allyl derivatives, which have shown anticancer activity both in vitro and in vivo in a large number of cancers, are bioactive molecules found in garlic, cinnamon, nutmeg, or mustard. In addition, synthetic products containing allyl fragments have been developed showing potent anticancer properties. Of particular note is the allyl derivative 17-AAG, which has been evaluated in Phase I and Phase II/III clinical trials for the treatment of multiple myeloma, metastatic melanoma, renal cancer, and breast cancer. In this Perspective, we compile extensive literature evidence with descriptions and discussions of the most recent advances in different natural and synthetic allyl derivatives that could generate cancer drug candidates in the near future.

Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds.

Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer's disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound 13a showed concentration- and time-dependent radical scavenging activity. Additionally, compounds 14a and 17a showed high activity in the melanoma and ovarian cancer cell lines, with LD50 values below 9.2 µM. Interestingly, in the AChEI test, compound 14a showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10-6 cm/s). Molecular dynamics simulations of the aspirin derivatives (14a and 14b) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as 14a, might become very promising candidates to treat both cancer and AD.

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases.

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain uncollected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Unfortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen-derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT.

Seleno-aspirin compound AS-10 promotes histone acetylation ahead of suppressing androgen receptor transcription, G1 arrest, and apoptosis of prostate cancer cells.

BACKGROUND: The novel selenium-aspirin compound AS-10 was recently reported by us with a cancer cell killing potency three orders of magnitude greater than aspirin in pancreatic cancer cell lines with caspase-mediated apoptosis and a reasonable selectivity against malignant cells. Although we also observed its cytocidal activity against PC-3 and DU145 androgen receptor (AR)-negative and P53-null/mutant aggressive human prostate cancer (PCa) cell lines in NCI-60 screen, the potential involvement and targeting of AR and P53 pathways that are intact in early-stage prostate carcinogenesis has not been examined, nor its primary molecular signaling after exposure. METHODS: Human LNCaP PCa cells with functional AR and intact P53 were used to examine their cell cycle and cell fate responses to AS-10 exposure and upstream molecular signaling events including histone acetylation as a known aspirin effect. The AR-positive 22Rv1 human PCa cells were used to validate key findings. RESULTS: In addition to confirming AS-10's superior cytocidal potency than aspirin against all four PCa cell lines, we report a rapid (within 5 min) promotion of histone acetylation several hours ahead of the suppression of AR and prostate-specific antigen (PSA, coded by KLK3 gene) in LNCaP and 22Rv1 cells. AS-10 decreased AR and KLK3 mRNA levels without impacting pre-existing AR protein degradation or nuclear translocation in LNCaP cells. Sustained exposure to AS-10 arrested cells predominantly in G1 , and induced caspase-mediated apoptosis without necrosis. The death induced by AS-10 in LNCaP cells was attenuated by nontranscriptional activation of P53 protein or Jun N-terminal Kinase cellular stress signaling and was mitigated modestly by glutathione-boosting antioxidant N-acetylcysteine. AS-10 synergized with histone deacetylase inhibitor SAHA to suppress AR/PSA abundance and kill LNCaP cells. RNA-seq confirmed AR suppression at the transcriptional level and suggested multiple oncogene, cyclin, and CDK/CKI transcriptional actions to contribute to the cellular consequences. CONCLUSIONS: AS-10 promotes histone acetylation as its probable primary mechanism of action to induce PCa cell-cycle arrest and apoptosis, regardless of AR and P53 status. Nevertheless, the inhibition of AR signaling through mechanisms distinct from canonical AR antagonists may hold promise for combinatorial use with androgen deprivation therapy regimens or AR-axis targeting drugs.

Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments.

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed.

Unveiling a New Selenocyanate as a Multitarget Candidate with Anticancer, Antileishmanial and Antibacterial Potential.

Currently, cancer, leishmaniasis and bacterial infections represent a serious public health burden worldwide. Six cinnamyl and benzodioxyl derivatives incorporating selenium (Se) as selenocyanate, diselenide, or selenide were designed and synthesized through a nucleophilic substitution and/or a reduction using hydrides. Ferrocene was also incorporated by a Friedel-Crafts acylation. All the compounds were screened in vitro for their antiproliferative, antileishmanial, and antibacterial properties. Their capacity to scavenge free radicals was also assessed as a first approach to test their antioxidant activity. Benzodioxyl derivatives 2a-b showed cytotoxicity against colon (HT-29) and lung (H1299) cancer cell lines, with IC50 values below 12 µM, and were also fairly selective when tested in nonmalignant cells. Selenocyanate compounds 1-2a displayed potent antileishmanial activity in L. major and L. infantum, with IC50 values below 5 µM. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 µg/mL. Ferrocene-containing selenide 2c was also identified as a potent antileishmanial agent with radical scavenging activity. Remarkably, derivative 2a with a selenocyanate moiety was found to act as a multitarget compound with antiproliferative, leishmanicidal, and antibacterial activities. Thus, the current work showed that 2a could be an appealing scaffold to design potential therapeutic drugs for multiple pathologies.