Four new piperine derivatives, PC1-PC4, were synthesized, and their structures were fully characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopies. Quantum chemical calculations were performed using density functional theory (DFT) with the B3LYP-D3/6-31G(d,p) and 6-311+G(2d,p) basis sets. Electronic properties, such as the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) and some global chemical reactivity descriptors, were evaluated to study the reactivity and stability of the compounds. 1H and 13C NMR chemical shifts were calculated by using the gauge-invariant atomic orbital (GIAO) method and compared with experimental values. In addition, the compounds were evaluated in an antifungal study against Candida, Trichophyton and Microsporum strains, and only PC4 showed 70% inhibition in ten tested strains, with a minimum inhibitory concentration (MIC) ranging from 1.23-2.46 μmol mL-1 and a minimum fungicide concentration (MFC) ranging from 9.84-19.68 μmol mL-1, and presented a fungistatic effect.

A series of fifteen new piperine-derived diesters was synthesized through the substitution reaction between the salt of piperic acid, obtained through piperine basic hydrolysis, with the δ-chloro-esters, obtained through the cleavage of tetrahydrofuran (THF) with acyl chlorides in the presence of ZnCl2. The final compounds were obtained with yields ranging from 50 to 84% and were characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). The new compounds were evaluated in silico in regard to their ADME (absorption, distribution, metabolism, and excretion) properties, and in vitro for their antimicrobial activity against bacteria strains (Staphylococcus aureus and Pseudomonas aeruginosas), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger). The results from the in silico studies of Lipinski’s rule of five showed that most compounds present good pharmacological possibilities, and the results from in vitro antimicrobial activity showed that 8 of the 15 synthesized compounds displayed antimicrobial activity, inhibiting the growth of 40-80% of tested strains, with a minimum inhibitory concentration (MIC) interval ranging from 1024 to 256 µg mL−1.

Ten imides derived from safrole, 4a-4j, were synthesized and their structures were fully characterized by infrared (IR) spectroscopy, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) analysis. Among the ten imides studied, eight are new. The compounds were evaluated in an in silico study and showed strong to moderate antifungal activity against various strains of Candida and Cryptococcus. In particular, compounds 4b, 4c and 4h exhibited strong antifungal activity, with minimum inhibitory concentration (MICs) between 0.17-0.73 µmol mL-1. The compound 4j exhibited antifungal activity with MIC 1.28 µmol mL-1 for all strains tested. In silico studies of the parameters of Lipinski’s rule of five indicated that these compounds are potential new drug candidates. The predict oral bioavailability can be evaluated through these parameters. In addition, a computational study helped assigning the stereochemistry of compound 4j, where the synthesized mixture is composed by two stereoisomers, 4j(1) (SRR) and 4j(2) (RSS).

Piperine, previously extracted from black pepper (Piper nigrum L.), was used as a precursor for the synthesis of twelve new diester derivatives. The final products were obtained through the bimolecular nucleophilic substitution reaction (SN2) of the alkyl 2-chloroacetates and the salt of piperic acid, obtained from the basic hydrolysis of piperine. The compounds were synthesized with yields of 55-84% and characterized by infrared spectroscopy and 1H and 13C nuclear magnetic resonance. The evaluation of the compounds’ potential as new drug candidates was done through an in silico study of ADME properties (absorption, distribution, metabolization and excretion) and evaluation of antimicrobial activity against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), yeasts (Candida albicans and Candida tropicalis) and filamentous fungi (Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger). The in silico study showed that the compounds were good drug candidates and antimicrobial evaluation demonstrated that 9 of the 12 compounds exhibited a minimum inhibitory concentration (MIC) ranging 1024-256 μg mL-1.

Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR), 1H and 13C nuclear magnetic resonance (NMR). The compounds were evaluated in an in silico study and showed strong to moderate antibacterial activity against several strains of Staphylococcus aureus. In particular, three compounds exhibited excellent antibacterial activity, with minimum inhibitory concentrations (MICs) between 16 and 64 µg mL-1. Furthermore, two of the nine compounds showed antifungal activity, with MIC of 1024 and 512 µg mL-1. In silico studies of the parameters of Lipinski's rule of five indicate that these compounds have potential to be new drug candidates.

A series of ten new compounds have been synthetized in satisfactory yields (85-95%) through the treatment of isopropyl mesoionic 1,3-thiazolium-5-thiolate with 2-chloro-N-arylacetamides and characterized by elemental analysis, infrared (IR), 1H and 13C nuclear magnetic resonance (NMR) spectroscopies. The newly synthesized compounds were evaluated as new drug candidates in in silico study and for their antifungal activity against several strains of Candida albicans. In silico study indicates that no compound has potential to be a new drug while four compounds showed medium to strong activity with minimum inhibitory concentration (MIC) range of 256-1024 µg mL-1.

Uma série de 21 derivados, 1,3,4-oxadiazolinas, foi sintetizada pela ciclização de N-acilhidrazonas com anidrido acético e avaliada in vitro quanto à sua atividade antifúngica contra seis espécies de Candida: Candida albicans (ATCC 90028 e LM V-42), Candida krusei (ATCC 6258 e LM 12 C) e Candida tropicalis (ATCC 13803 e LM 14). As espécies de Candida foram consideradas sensíveis a uma série dos compostos, os quais inibiram o crescimento de 50 a 90%, com um intervalo de concentração inibitória mínima (MIC) de 64 a 512 µg mL-1. As estruturas dos compostos foram totalmente confirmadas e caracterizadas pelas técnicas de infravermelho com transformada de Fourier (FTIR), ressonância magnética nuclear (NMR) de ¹H e 13C, e espectrometria de massa (MS).

A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains: Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C. tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration (MIC) in the range of 64-512 µg mL-1. The compounds' structures were fully confirmed and characterized by Fourier transform infrared spectroscopy (FTIR), ¹H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS).