Molecular Modeling and In Vitro Evaluation of Piplartine Analogs against Oral Squamous Cell Carcinoma.

Cancer is a principal cause of death in the world, and providing a better quality of life and reducing mortality through effective pharmacological treatment remains a challenge. Among malignant tumor types, squamous cell carcinoma-esophageal cancer (EC) is usually located in the mouth, with approximately 90% located mainly on the tongue and floor of the mouth. Piplartine is an alkamide found in certain species of the genus Piper and presents many pharmacological properties including antitumor activity. In the present study, the cytotoxic potential of a collection of piplartine analogs against human oral SCC9 carcinoma cells was evaluated. The analogs were prepared via Fischer esterification reactions, alkyl and aryl halide esterification, and a coupling reaction with PyBOP using the natural compound 3,4,5-trimethoxybenzoic acid as a starting material. The products were structurally characterized using 1H and 13C nuclear magnetic resonance, infrared spectroscopy, and high-resolution mass spectrometry for the unpublished compounds. The compound 4-methoxy-benzyl 3,4,5-trimethoxybenzoate (9) presented an IC50 of 46.21 µM, high selectively (SI > 16), and caused apoptosis in SCC9 cancer cells. The molecular modeling study suggested a multi-target mechanism of action for the antitumor activity of compound 9 with CRM1 as the main target receptor.

Antimicrobial Activity of 4-Chlorocinnamic Acid Derivatives.

The microbial resistance of fungi and bacteria is currently considered a major public health problem. Esters derived from cinnamic acid have a broad spectrum of pharmacological properties that include antimicrobial activity. In this study, a collection of structurally related 4-chlorocinnamic acid esters was prepared using Fischer esterification reactions, alkyl or aryl halide esterification, and Mitsunobu and Steglich reactions. All of the esters were submitted to antimicrobial tests against strains of the species Candida albicans, Candida glabrata, Candida krusei, Candida guilliermondii, Pseudomonas aeruginosa, and Staphylococcus aureus. The compounds also were subjected to molecular docking study with the enzyme 14α-demethylase. Twelve esters derived from 4-chlorocinnamic acid were obtained, with yields varying from 26.3% to 97.6%, three of which were unpublished. The ester methyl 4-chlorocinnamate (1) presented activity against S. aureus at the highest concentration tested. In the antifungal evaluation, all of the esters were bioactive, but methoxyethyl 4-chlorocinnamate (4) and perillyl 4-chlorocinnamate (11) were the most potent (MIC = 0.13 and 0.024 µmol/mL, respectively). The data of molecular docking suggested that all the compounds present good affinity towards the active site related to antifungal activity. Therefore, the esters tested may be inhibitors of the enzyme 14α-demethylase. In addition, the results demonstrate that substituents of short alkyl chains with presence of heteroatom, such as oxygen, or those with a perillyl type terpenic substructure promote better antifungal profiles.

Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants.

Depression is a disease that has affected a high proportion of the world's population and people of different ages, incapacitating them from good performance at work and in social relationships, and causing emotional disorders to millions of families. Therefore, the search for new therapeutic agents is considered a priority for the discovery of more effective forms of treatment. In this review, studies of essential oils and their constituents in experimental models related to depression are discussed. The mechanisms of action of the oils and the presence of psychoactive constituents in their chemical compositions are discussed. The data in the review show the therapeutic potential of essential oils and their chemical constituents for use in depressive disorders. Advanced studies using humans are needed to confirm the antidepressant properties described in animals.