Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used in an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objectives: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "inhouse" library of both AGH and TSC derivatives and their structurally-related compounds. Methods: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD^® software. Results: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC₅₀ values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are in progress, which will help choose the best hits for in vivo experiments.

The discovery of antibiotics was a revolutionary feat that provided countless health bene-fits. The identification of penicillin by Alexander Fleming initiated the era of antibiotics, represent-ed by constant discoveries that enabled effective treatments for the different classes of diseases caused by bacteria. However, the indiscriminate use of these drugs allowed the emergence of re-sistance mechanisms of these microorganisms against the available drugs. In addition, the constant discoveries in the 20th century generated a shortage of new molecules, worrying health agencies and professionals about the appearance of multidrug-resistant strains against available drugs. In this context, the advances of recent years in molecular biology and microbiology have allowed new per-spectives in drug design and development, using the findings related to the mechanisms of bacterial resistance to generate new drugs that are not affected by such mechanisms and supply new mole-cules to be used to treat resistant bacterial infections. Besides, a promising strategy against bacterial resistance is the combination of drugs through adjuvants, providing new expectations in designing new antibiotics and new antimicrobial therapies. Thus, this manuscript will address the main mech-anisms of bacterial resistance under the understanding of medicinal chemistry, showing the main active compounds against efflux mechanisms, and also the application of the use of drug delivery systems, and finally, the main potential natural products as adjuvants or with promising activity against resistant strains.

Drought stress is a critical factor affecting plant growth and development. Understanding the effects of drought on the physiology of medicinal plants can contribute to the implementation of better water management techniques and promote a sustainable production. This study aimed to evaluate the influence of water stress on the growth and development of Mentha spicata L. plants. A completely randomized design was used, with two water conditions: irrigated and non-irrigated. The water deficit negatively affected the dry weight of roots and shoots, with a decrease in the transpiration rate and chlorophyll content, potentially impairing the photosynthetic activity. However, the essential oil production was not affected in plants subjected to water deficiency, indicating that the essential oil production may be more resilient to drought stress in this species.

Cereus jamacaru DC. is an endemic cactus of the Brazilian semiarid region empirically used by humans for forage, food and medicinal purposes. In this paper, we characterize the physicochemical and phytochemical profile of the C. jamacaru cladode and fruits, outlining their nutritional implications. We evaluate the basic physicochemical characteristic of the fruits and the main classes of chemical compounds present in aqueous and ethanolic extracts from cladode, peel, and pulp of ripe and semi-ripe fruits through qualitatively and quantitatively methods. We analyze the data through descriptive statistics and variance analysis. The fruits have appropriate pH, acidity, and total soluble solid levels for the fruit processing industry and fresh consumption. We identified the presence of saponins, tannins, flavones, flavonols, and xanthones in all samples, but alkaloids and steroids were both detected in cladodes exclusively. The phenolic compound and flavonoid contents vary according to the extraction method and sample class. The cladodes and pulp of ripe fruits have the highest flavonoid levels, while the content of phenolic compounds had a high level in peels of ripe and semi-ripe fruits. The presence of these bioactive compounds implies that C. jamacaru products have relevant pharmacological interest and functionality for human (fruits) and domestic ruminant (cladodes) food. These applications can boost the agricultural-economic exploration of C. jamacaru and contribute to income generation, and improve human and animal nutrition.