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The biological activity of essential oils and their major components is well documented. Essential oils such as oregano and cinnamon are known for their effect against bacteria, fungi, and even viruses. The mechanism of action is proposed to be related to membrane and external cell structures, including cell walls. This study aimed to evaluate the biological activity of seven essential oils and eight of their major components against Gram-negative and Gram-positive bacteria, filamentous fungi, and protozoans. The antimicrobial activity was evaluated by determination of the Minimal Inhibitory Concentration for Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Salmonella Typhimurium, Shigella sonnei, Aspergillus niger, Aspergillus ochraceus, Alternaria alternata, and Fusarium oxysporium, the half-maximal inhibitory concentration (IC50) for Trypanosoma cruzi and Leishmania mexicana, and the median lethal dose (LD50) for Giardia lamblia. Results showed that oregano essential oil showed the best antibacterial activity (66–100 µg/mL), while cinnamon essential oil had the best fungicidal activity (66–116 µg/mL), and both showed excellent antiprotozoal activity (22–108 µg/mL). Regarding the major components, thymol and carvacrol were also good antimicrobials (23–200 µg/mL), and cinnamaldehyde was an antifungal compound (41–75 µg/mL). The major components were grouped according to their chemical structure as phenylpropanoids, terpenoids, and terpinenes. The statistical analysis of the grouped data demonstrated that protozoans were more susceptible to the essential oils, followed by fungi, Gram-positive bacteria, and Gram-negative bacteria. The analysis for the major components showed that the most resistant microbial group was fungi, which was followed by bacteria, and protozoans were also more susceptible. Principal Component Analysis for the essential oils demonstrated the relationship between the biological activity and the microbial group tested, with the first three components explaining 94.3% of the data variability. The chemical structure of the major components was also related to the biological activity presented against the microbial groups tested, where the three first principal components accounted for 91.9% of the variability. The external structures and the characteristics of the cell membranes in the different microbial groups are determinant for their susceptibility to essential oils and their major components

Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted drug design has been implemented in scientific research for drug repurposing, allowing for reduced costs and time. Therefore, the objective of this work was to search for analogs of FDA-approved drugs with activity against Trypanosoma cruzi through ligand-based virtual screening and their biological evaluation against blood trypomastigotes. The compound TD-095 (LC50 = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC50 = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC50 = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC50 = 69.70 and 39.69 µM) and LK-284 (LC50 = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs. Molecular dynamics simulations predicted the stability of the compounds in complex with their respective proteins. Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA.

In this study, a drug repurposing strategy was implemented with the aim of identifying new trypanocidal agents against Trypanosoma cruzi (T. cruzi). A total of 924 Food and Drug Administration (FDA)-approved drugs were screened by molecular docking on three sites of trypanothione synthetase (TS), including the catalytic site, a blind docking site, and a potential allosteric site. Selected compounds were further evaluated through in vitro and in vivo assays. Tadalafil, Zafirlukast, Raltegravir, and Olmesartan had better trypanocidal activity than the reference drugs Benznidazole and Nifurtimox in the in vitro evaluation against the trypomastigote form. Additionally, these drugs were able to decrease parasitemia by 20–50% in mice in an acute treatment. Molecular dynamics simulations (MDS) at 120 ns helped link findings from in vitro/in vivo experiments to a potential mechanism of action targeting T. cruzi trypanothione synthetase (TcTS). Therefore, the results encourage the use of these drugs to develop new anti-T. cruzi agents.

Aedes aegypti is a vector for the arbovirus responsible for yellow fever, Zika and Chikungunya virus. Essential oils and their constituents are known for their larvicidal properties and are strong candidates for mosquito control. This work aimed to develop a quantitative structure–activity study and molecular screening for the search and design of new larvicidal agents. Twenty-five monoterpenes with previously evaluated larvicidal activity were built and optimized using computational tools. QSAR models were constructed through genetic algorithms from the larvicidal activity and the calculation of theoretical descriptors for each molecule. Docking studies on acetylcholinesterase (AChE) and sterol carrier protein (SCP-2) were also carried out. Results demonstrate that the epoxide groups in the structure of terpenes hinder larvicidal activity, while lipophilicity plays an important role in enhancing biological activity. Larvicidal activity correlates with the interaction of the sterol-carrier protein. Of the 25 compounds evaluated, carvacrol showed the highest larvicidal activity with an LC50 of 8.8 µg/mL. The information included in this work contributes to describing the molecular, topological, and quantum mechanical properties related to the larvicidal activity of monoterpenes and their derivatives.

American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects approximately 6–7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients’ treatment abandonment. Therefore, there is a need for new and better treatments. In this work, the molecular docking of nine hundred twenty-four FDA-approved drugs on three different sites of trypanothione reductase of T. cruzi (TcTR) was carried out to find potential trypanocidal agents. Finally, biological evaluations in vitro and in vivo were conducted with the selected FDA-approved drugs. Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20–50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against T. cruzi infection.

Background: Parasitic diseases, particularly Chagas disease caused by Trypanosoma cruzi, primarily affect developing countries but are now spreading to wealthier nations due to changing migration patterns. With approximately 8 to 9 million cases annually and a rise in drug resistance and side effects, there is an urgent need for new therapeutic approaches. Objectives: This study aimed to identify potential pharmacological compounds to target the TATA Binding Protein (TBP) of T. cruzi. Methods: Over eleven thousand FDA-approved pharmacological compounds were analyzed using in silico methods, including homology modeling, molecular docking, and molecular dynamics simulations. In addition, in vitro assays were conducted to assess the trypanocidal activity of promising candidates against T. cruzi epimastigotes and their selectivity toward macrophage J774.2. Results: Two compounds, DB00890 and DB07635, emerged as promising candidates, demonstrating significant potential against T. cruzi TBP. Compound DB00890 had trypanocidal activity against T. cruzi epimastigotes, with IC50 values of 70.4 µM (SI 2.84) and 37.3 µM (SI 5.36) for the NINOA and A1 strains, respectively. Conclusions: Our findings suggest DB00890 is a promising candidate for the development of new agents against Chagas disease, with the potential for targeted therapies that minimize side effects. These results provide a strong foundation for further research into novel treatments for parasitic diseases caused by T. cruzi.

Chagas disease, caused by the protozoan Trypanosoma cruzi, represents a significant public health challenge, particularly in Latin America’s endemic regions. The limited efficacy and frequent adverse effects of current treatments underscore the need for novel therapeutic options. This research explores marine natural compounds as potential candidates for Chagas disease treatment using virtual screening and in silico evaluation methods. Techniques such as molecular docking, drug-likeness evaluation, and pharmacokinetic analysis were employed to identify promising anti-parasitic compounds. Among the candidates, chandrananimycin A, venezueline A, and dispacamide demonstrated high binding affinities to key targets in T. cruzi alongside favorable docking scores and compliance with essential drug-likeness criteria. Pharmacokinetic profiling further supported their therapeutic potential, revealing desirable properties like effective absorption and minimal toxicity. These findings underscore the promise of marine-derived compounds as a valuable source of new drugs, emphasizing the need for further in vitro and in vivo investigations to elucidate their molecular mechanisms and optimize their development as viable treatments for Chagas disease.

Infection with the protozoan parasite Trypanosoma cruzi causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency of these drugs for its safer use. Background/Objective: Glyburide, glipizide, and gliquidone, hypoglycemic drugs for diabetes treatment, were previously predicted to bind to dihydrofolate reductase-thymidylate synthase from T. cruzi by in silico docking analysis; they also showed antiproliferative effects against T. cruzi epimastigotes, the stage of the insect vector. In the present study, the potential parasiticidal effect of these antidiabetic drugs was tested in monotherapy and bi-therapy with BNZ in human cells in vitro and in animals. Methods: Evaluation was performed in (a) a model of in vitro infection of T. cruzi trypomastigotes using human fibroblasts as host cells and (b) in mice infected with T. cruzi. Results: The antidiabetic drugs in monotherapy showed antiparasitic effects in preventing infection progression (trypomastigotes release), with an IC50 of 8.4–14.3 µM in comparison to that of BNZ (0.26 µM) in vitro. However, in bi-therapy, the presence of just 0.5 or 1 µM of the antidiabetics decreased the BNZ IC50 by 5–10 times to 0.03–0.05 µM. Remarkably, the antidiabetic drugs in monotherapy decreased the infection in mice by 40–60% in a similar extent to BNZ (80%). In addition, the combination of BNZ plus antidiabetics perturbed the antioxidant metabolites in epimastigotes. Conclusions: These results identified antidiabetics as potential drugs in combination therapy with BNZ to treat T. cruzi infection.

A series of 2-benzylsulfanyl benzothiazole (BTA) derivatives were synthesized and fully characterized and in vitro tested against two strains of T. cruzi (NINOA and INC-5), exhibiting good activities at low concentrations.

The larvicidal activity of essential oils cinnamon (Cinnamomum verum J. Presl), Mexican lime (Citrus aurantifolia Swingle) cumin (Cuminum cyminum Linnaeus), clove (Syzygium aromaticum (L.) Merr. & L.M.Perry), laurel (Laurus nobilis Linnaeus), Mexican oregano (Lippia berlandieri Schauer) and anise (Pimpinella anisum Linnaeus)) and their major components are tested against larvae and pupae of Culex quinquefasciatus Say. Third instar larvae and pupae are used for determination of lethality and mortality. Essential oils with more than 90% mortality after a 30-min treatment are evaluated at different time intervals. Of the essential oils tested, anise and Mexican oregano are effective against larvae, with a median lethal concentration (LC50) of 4.7 and 6.5 µg/mL, respectively. Anise essential oil and t-anethole are effective against pupae, with LC50 values of 102 and 48.7 µg/mL, respectively. Oregano essential oil and carvacrol also have relevant activities. A kinetic analysis of the larvicidal activity, the oviposition deterrent effect and assays of the effects of the binary mixtures of chemical components are undertaken. Results show that anethole has synergistic effects with other constituents. This same effect is observed for carvacrol and thymol. Limonene shows antagonistic effect with β-pinene. The high larvicidal and pupaecidal activities of essential oils and its components demonstrate that they can be potential substitutes for chemical compounds used in mosquitoes control programs.