Considering the relevance of natural products to the development of new drugs, this study focuses on the species Sida rhombifolia (L.), Malvaceae, widely used as a traditional remedy in several countries. The species is used to treat several diseases such as fevers, skin diseases, stomach pain, diarrhea, gum infection, conjunctivitis, urinary infections and inflammation. Many researchers around the word have investigated its pharmacological potential, and many uses have been confirmed. In spite of that, the phytochemical composition of its extracts is still poorly investigated. This research aims to make advances on the understanding of the constituents of S. rhombifolia identifying its alkaloidal compounds using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-QTOF-MS/MS). By analyzing its alkaloidal fraction, it was possible to identify: 11-cryptolepine carboxylic acid (1), cryptolepine (2), quindoline (3), 11 methoxyquidoline (4), quindolinone (5), cryptolepinone (6), and 11-quindoline methyl ester (7). The alkaloids 1 and 7 are being reported for the first time from Sida genus. Based on the antimicrobial potential of cryptolepinone-type alkaloids, we prepared by semi-synthesis two cryptolepinone derivatives: 10-methylcryptolepinone (8) and the unreported compound 10-ethylcryptolepinone (9). Both derivatives were tested against fungal and bacterial strains and 10-methylcryptolepinone (8) showed strong activity against Cryptococcus neoformans, Candida albicans, Candida tropicalis, Aspergillus fumigatus and Aspergillus flavus.

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.

Abstract Aspergillus genus causes many diseases, and the species Aspergillus flavus is highly virulent. Treatment of aspergillosis involves azole derivatives such as voriconazole and polyenes such as amphotericin B. Due to an increase in fungal resistance, treatments are now less effective; the search for new compounds with promising antifungal activity has gained importance. The aims of this study were to evaluate the effects of the synthetic amide 2-chloro-N-phenylacetamide (A1Cl) against strains of Aspergillus flavus and to elucidate its mechanism of action. Thus, the minimum inhibitory concentration, minimum fungicidal concentration, conidial germination, associations with antifungal agents, cell wall activities, membrane activities and molecular docking were evaluated. A1Cl presented antifungal activity against Aspergillus flavus strains with a minimum inhibitory concentration of between 16 and 256 μg/mL and a minimum fungicidal concentration between 32 and 512 μg/mL. The minimum inhibitory concentration of A1Cl also inhibited conidial germination, but when associated with amphotericin B and voriconazole, it promoted antagonistic effects. Binding to ergosterol on the fungal plasma membrane is the likely mechanism of action, along with possible inhibition of DNA synthesis through the inhibition of thymidylate synthase. It is concluded that the amide 2-chloro-N-phenylacetamide has promising antifungal potential.

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.

New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 µg mL−1 against all fungal strains, while 7h showed a very good MIC of 256 µg mL−1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 µg mL−1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 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.

Abstract Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

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.

RESUMOAo longo do tempo, se modificou a etiologia das onicomicoses, leveduras do gênero Candida têm emergido como agentes etiológicos importantes. O objetivo desse trabalho foi determinar a frequência de onicomicoses causadas por leveduras em João Pessoa, Paraíba, Brasil de 1999 a 2010. Um estudo retrospectivo de janeiro de 1999 a dezembro de 2010 avaliou os resultados de exames micológicos diretos (EMD) positivos para leveduras provenientes de onicomicoses, realizados no Laboratório Clínico Hemato(r). As mulheres foram as mais afetadas por onicomicoses, as unhas dos pés são os alvos preferidos e ocorrem preferencialmente em adultos. As leveduras prevalentes foram Candida tropicalis e C. krusei.

ABSTRACTOver time, as the etiology of onychomycosis has developed, yeasts from the genus Candida have emerged as important etiological agents. This study aimed to determine the frequency of yeast caused onychomycosis in Joao Pessoa, Paraíba, Brazil from 1999 to 2010. A retrospective study from January 1999 to December 2010 evaluated the results of onychomycosis positive direct mycological exams (DME) - for yeast and realized in the Hemato(r) Clinical Laboratory. Women were the most affected by onychomycosis which occur preferentially in adults, and the toenails are the favorite yeast targets. The prevalent yeasts were Candida tropicalis and C. krusei.

Este é o primeiro relato de atividade antibacteriana de Hyptis martiusii Benth. Neste estudo, o extrato etanólico de H. martiusii foi avaliado para atividade antimicrobiana contra linhagens de Escherichia coli, Pseudomonas aeruginosa e Staphylococcus aureus. O crescimento de todas as bactérias testadas foi inibido pelo extrato. O diâmetro das zonas de inibição variaram de 13 - 20 mm. Os valores da CIM e CBM variaram de 128 a > 1024 mg/mL e 256 a > 1024 mg/mL, respectivamente. Devido a isso, podemos indicar que o extrato etanólico de H. martiusii pode ser usado como um agente anti-Staphylococcus. Quando comparado com outros antibióticos como meticilina e gentamicina, o extrato foi mais efetivo, demonstrando ser um promissor agente antibacteriano.

This is the first report about the antibacterial activity of Hyptis martiusii Benth. In this study the ethanol extract of H. martiusii was tested for its antimicrobial activity against strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The growth of all bacterial strains tested was inhibited by the extract. The diameter of inhibition zones varied from 13 to 20 mm for the extract. The MIC and MBC values ranged from 128 to > 1024mg/mL and 256 to > 1024 mg/mL, respectively. It is therefore suggested that extracts from H. martiusii could be used as an anti-Staphylococcus agent. Compared with methicillin and gentamicin, the extract was more effective, being a promising antibacterial agent.

Otite externa aguda é a inflamação do conduto auditivo externo, e plantas medicinais podem ser utilizadas, na cultura popular, para seu tratamento. OBJETIVO: Avaliar atividade antimicrobiana in vitro de Aleolanthus suaveolens, Caryophyllus aromaticus, Cymbopogon citratus, Matricaria chamomila, Pithecellobium avaremotemo, Plectranthus amboinicus e Ruta graveolens sobre agentes etiológicos de otite externa. CASUÍSTICA E MÉTODOS: A concentração inibitória mínima de extratos e óleos destas plantas foi obtida em amostras de otite externa. RESULTADOS: Staphylococcus aureus em 10 culturas, Pseudomonas aeruginosa em 8, Pseudomonas aeruginosa e Staphylococcus aureus, em associação, em 5 culturas e Candida albicans e Candida krusei em 4 culturas. P. aeruginosa foi resistente a todos os extratos e óleos essenciais testados; os extratos de A. suaveolens, P. avaremotemo e de R. graveolens foram inativos, o óleo essencial de C. aromaticus e M. chamomila foram ativos contra 3 cepas de S. aureus e as cepas de Candida; Sete das cepas de S. aureus foram sensíveis ao extrato de P. amboinicus, mas o óleo não mostrou atividade, 4 cepas de S.aureus e as cepas de Candida foram sensíveis ao óleo essencial de R. graveolens. CONCLUSÃO: Algumas plantas apresentaram resultados satisfatórios, dependendo do agente etiológico, porém se faz necessário estudos mais detalhados, para melhorar o aproveitamento destas plantas.

Acute Otitis Externa is an inflammation of the outer auditory meatus, and according to popular saying, medicinal plant extracts can be used in its treatment. AIM: to assess the in vitro antimicrobial activity of the following plants: Aleolanthus suaveolens; Caryophyllus aromaticus; Cymbopogon citratus; Matricaria chamomila; Pithecellobium avaremotemo; Plectranthus amboinicus and Ruta graveolens on the germs that cause otitis externa. MATERIALS AND METHODS: the minimum inhibitory concentration of extracts and oils from these plants was obtained from otitis externa samples. RESULTS: Staphylococcus aureus in 10 cultures, Pseudomonas aeruginosa in 8, Pseudomonas aeruginosa and Staphylococcus aureus together in 5 cultures and Candida albicans and Candida krusei in 4 cultures. P. aeruginosa was resistant to all oils and extracts tested; extracts from A. suaveolens, P. avaremotemo and R. graveolens were inactive; the essential oil from C. aromaticus and M. chamomila were active against 3 strains of S. aureus and the Candida strains; seven of the S. aureus strains were sensitive to the P. amboinicus extract; however, the oil was inactive against 4 S. aureus strains and the Candida strains were sensitive to the R. graveolens essential oil. CONCLUSION: depending on the etiological agent, some plants presented satisfactory results, however we still need more detailed studies in order to better use these plants.

Diante da problemática da resistência microbiana as pesquisas apontam para o uso de novos antibióticos que sejam eficazes ante os patógenos emergentes. Este trabalho objetiva testar frente a bactérias gram-positivas (Staphylococcus aureus), bactérias gram-negativas (Escherichia coli e Pseudomonas aeruginosa) e fungos leveduriformes (Candida albicans), a atividade antimicrobiana e a concentração inibitória mínima (CIM) de fitoconstituintes de Ocotea duckei Vattimo, do lapachol, seus derivados semi-sintéticos, alfa-lapachona, beta-nor-lapachona, beta-lapachona, alfa-nor-lapachona, beta-3-iodo-lapachona e alfa-3-iodo-lapachona, assim como 07 derivados nitrogenados obtidos a partir do lapachol por semi-síntese e de imidas cíclicas similares ao alcalóide filantimida. Os resultados obtidos estimulam o aprofundamento dos estudos para algumas dessas substâncias a exemplo do lapachol e seus análogos que demonstraram atividade antimicrobiana, de modo que os produtos que se apresentaram ativos para S. aureus, foram lapachol e o extrato etanólico de Ocotea duckei, para E. coli foi a iangambina e para a Candida albicans foram as imidas. As demais substâncias não apresentaram atividade antimicrobiana para as cepas testadas.

Regarding the problem of microbial resistance, the researches point to the use of new antibiotic which can be active against the emergent pathogens. This work aims to test the activity against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli e Pseudomonas aeruginosa) and leveduriform fungi (Candida albicans), and also the Minimum Inhibitory Concentration (MIC) of the constituent of Ocotea duckei Vattimo, lapachol and its synthetic derivatives alpha-lapachone, beta-nor-lapachone, beta-lapachone, alpha-nor-lapachone, beta-3-iodin-lapachone and alpha-3-iodin-lapachone, as well as seven nitrogenated derivatives of lapachol obtained through semi synthesis. The achieved results stimulate the deepening of the studies for some of theses substances such as lapachol and its analogous which demonstrated antimicrobial activity. The substances which were active against S. aureus, were lapachol and the ethanolic extract of Ocotea duckei Vattimo, against Escherichia coli iangambin and against C. albicans the imides. The other substances did not show any activity against the tested bacteria.

Os óleos essenciais apresentam atividade antimicrobiana contra uma variedade de bactérias e fungos, incluindo espécies resistentes a antibióticos e antimicóticos. Neste contexto, este trabalho objetiva a avaliação da atividade de antimicrobiana do óleo essencial de Mentha x villosa Hudson (hortelã-da-folha-miúda) - seu componente majoritário (rotundifolona) e quatro análogos sintéticos da rotundifolona (epóxi-limoneno epóxi-pulegona, epóxi-carvona e (+)-pulegona) frente a cepas padrão de Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 76645 e uma cepa de Staphylococcus aureus meticilina - resistente - MRSA (171c) de clínica humana. Como método, foi utilizada a difusão em placas com médio sólido. Os resultados mostraram que o óleo de Mentha x villosa, rotundifolona, epóxi-limoneno e (+)-pulegona, são semelhante em função da atividade antimicrobiana para as cepas de S. aureus e C.albicans testadas. Todos os produtos apresentaram potencial antimicrobiano com atividade antibacteriana para S. aureus ATCC 25923 e atividade antifúngica para C. albicans ATCC 76645. Nenhum dos produtos apresentou atividade antimicrobiana para as cepas de E. coli ATCC 25922 e P. aeruginosa ATCC 27853, representantes das bactérias Gram negativas.

Essential oils present antimicrobial activity against a variety of bacteria and yeasts, including species resistant to antibiotics and antifungicals. In this context, this work aims at the evaluation of the antimicrobial activity of the essential oil of Mentha x villosa Hudson ("hortelã da folha miúda"), its major component (rotundifolone) and four similar analogues of rotundifolone (limonene oxide, pulegone oxide, carvone epoxide and (+)-pulegone) against strain standards of Staphylococcus aureus ATCC 25923, E. coli ATCC 25922, Pseudomona aeruginosa ATCC 27853, Candida albicans ATCC 76645 and one strain of meticilin - resistant Staphylococcus aureus - MRSA (171c) from human clinic. The method of the diffusion in plates with solid medium was used. The results showed that the oil of Mentha x villosa, rotundifolone, limonene oxide and (+)-pulegone, are similar regarding the antimicrobial activity against the tested strains of S. aureus and C. albicans. All of the products present antimocrobial potential with antibacterial activity for S. aureus ATCC 25923 and antifungal activity for C. albicans ATCC 76645. None of the products presented antimicrobial activity for the strains of E. coli ATCC 25922 and P. aeruginosa ATCC 27853, representatives of the Gram negative bacteria.