Antibacterial and antibiofilm activities of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one derivatives against multidrug-resistant Staphylococcus aureus clinical isolates.

AIMS: Antimicrobial resistance is one of the highest priorities in global public health with Staphylococcus aureus among the most important microorganisms due to its rapidly evolving antimicrobial resistance. Despite all the efforts of antimicrobial stewardship, research and development of new antimicrobials are still imperative. The thiazolidine ring is considered a privileged structure for the development of new antimicrobials. This study aimed to compare the antibacterial effects of two analogue series of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one against multidrug-resistant Staph. aureus clinical isolates. METHODS AND RESULTS: The derivatives 1a, 2a and 2b exhibited MIC between 1-32 µg ml-1 , with time-to-kill curves showing a bactericidal effect up to 24 h. In the antibiofilm assay, the most active derivatives were able to inhibit about 90% of biofilm formation. The 4-thioxo-thiazolidine-2-one derivatives were more active against planktonic cells, while the thiazolidine-2,4-dione derivatives were able to disrupt about 50% of the preformed biofilm. In the in vivo infection model using Caenorhabditis elegans as a host, the derivatives 1a, 2a and 2b increased nematode survival with a concentration-dependent effect. Exposure of Staph. aureus to the derivatives 2a and 2b induced surface changes and decrease cell size. None of the derivatives was cytotoxic for human peripheral blood mononuclear cells (PBMC) but showed moderate cytotoxicity for L929 fibroblasts. CONCLUSION: The 5-(3,4-dichlorobenzylidene)-4-thioxothiazolidin-2-one (2b) was the most active derivative against Staph. aureus and showed higher selective indices. SIGNIFICANCE AND IMPACT OF THE STUDY: 4-thioxo-thiazolidin-2-one is a promising scaffold for the research and development of new antimicrobial drugs against multidrug-resistant Staph. aureus.

Anticancer activity of monoterpenes: a systematic review.

Secondary metabolites have been recognized for centuries as medicinal agents, in particular monoterpenes which have been the target of research in the discovery of antineoplastic drugs, as they have potential antitumor effect and low toxicity and are used as additives in foods and cosmetics. Another advantage of monoterpenes is structural diversity, which gives greater plasticity when interacting with cells. The purpose of this review was to summarize and critically discuss the anticancer potential of monoterpenes and their respective mechanisms of action. A systematic review of articles in the MEDLINE/PubMed, Web of Science, Scopus and Science Direct electronic databases was independently conducted by three reviewers using the combination of the following keywords: monoterpenes AND anticancer AND in vitro. Restriction in selecting articles followed pre-established inclusion and exclusion criteria by the reviewers, and also a time limitation with works published between 2015 and 2019 being selected. In total, 39 works were deemed eligible for inclusion in the final review. Monoterpenes have cytotoxic activity in a wide variety of tumor cell lines, and mainly appear to exert this effect by inducing apoptosis caused by oxidative stress. In addition, improved use of monoterpenes when used in drug delivery systems and the synergistic effect with conventional chemotherapeutic drugs are reported. These findings validate this class of compounds as a promising source of chemotherapeutic drugs yet to be explored.

Production of cupcake-like dessert containing microbial biosurfactant as an emulsifier.

This work describes the application of the biosurfactant from Candida bombicola URM 3718 as a meal additive like cupcake. The biosurfactant was produced in a culture medium containing 5% sugar cane molasses, 5% residual soybean oil and 3% corn steep liquor. The surface and interfacial tension of the biosurfactant were 30.790 ± 0.04 mN/m and 0.730 ± 0.05 mN/m, respectively. The yield in isolated biosurfactant was 25 ± 1.02 g/L and the CMC was 0.5 g/L. The emulsions of the isolated biosurfactant with vegetable oils showed satisfactory results. The microphotographs of the emulsions showed that increasing the concentration of biosurfactant decreased the oil droplets, increasing the stability of the emulsions. The biosurfactant was incorporated into the cupcake dessert formulation, replacing 50%, 75% and 100% of the vegetable fat in the standard formulation. Thermal analysis showed that the biosurfactant is stable for cooking cupcakes (180 °C). The biosurfactant proved to be promising for application in foods low in antioxidants and did not show cytotoxic potential in the tested cell lines. Cupcakes with biosurfactant incorporated in their dough did not show significant differences in physical and physical-chemical properties after baking when compared to the standard formulation. In this way, the biosurfactant has potential for application in the food industry as an emulsifier for flour dessert.

Mouthwash containing a biosurfactant and chitosan: An eco-sustainable option for the control of cariogenic microorganisms.

The aim of the present study was to determine the antimicrobial action and toxicity of mouthwashes formulated with a biosurfactant, chitosan of a microbial origin and peppermint (Mentha piperita) essential oil (POE). Chitosan was extracted from the biomass of a fungus from the order Mucorales grown in yam bean broth. Three biosurfactants produced by Pseudomonas aeruginosa UCP 0992 (PB), Bacillus cereus UCP 1615 (BB) and Candida bombicola URM 3718 (CB) were tested. Six mouthwashes were prepared, the active ingredients of which were the biosurfactant, chitosan and POE. The minimum inhibitory concentration (MIC) was determined for the test substances separately, in combinations and in the mouthwash formulas. The toxicity of the mouthwashes was tested using MTT (3-(4,5-dimethylthiazole-2-il)-2,5-diphenyltetrazolium bromide) for the L929 (mouse fibroblast) and RAW 264.7 (mouse macrophage) cell lines. All substances tested had a MIC for cariogenic microorganisms. The combinations of the CB and PB biosurfactants with chitosan demonstrated an additive effect on the majority of microorganisms tested. The toxicity of the mouthwashes was significantly lower than that of the commercial mouthwash. The present findings demonstrate that mouthwashes containing natural products constitute a safe, effective, natural alternative to commercially available mouthwashes for the control of oral microorganisms.

Characterization of the biochemical, physiological, and medicinal properties of Streptomyces hygroscopicus ACTMS-9H isolated from the Amazon (Brazil).

Actinomycetes are known to produce numerous secondary bioactive metabolites of pharmaceutical interest. The purpose of this study was to isolate, characterize, and investigate the antibacterial, antifungal, and anticancer activities of metabolites produced by Actinobacteria isolated from the rhizosphere of Paullinia cupana. The Actinobacteria was identified as Streptomyces hygroscopicus ACTMS-9H. Based on a bioguided study, the methanolic biomass extract obtained from submerged cultivation had the most potent antibacterial, antifungal, and cytotoxic activities. This extract was partitioned with n-hexane, ethyl acetate, and 2-butanol. Elaiophylin was isolated from the methanolic biomass extract, and its molecular formula was determined (C54H88O18) based on 1H and 13C NMR, IR and MS analyses. The 2-butanol phase was fractionated into four fractions (EB1, EB2A, EB2B, and EB3M). Chemical prospecting indicated the presence of alkaloids, saponins, and reducing sugars in the methanolic extract and 2-butanol phase. The elaiophylin displayed anticancer activity in HEp-2 and HL-60 cells with an IC50 of 1 µg/mL. The EB1 fraction was selectively toxic to HL-60 cells with IC50 of 9 ng/mL. Bioautography showed that the EB1 fraction contained an alkaloid with antibacterial and antifungal activities (MIC values ≤1.9 and <3.9 µg/mL, respectively). In conclusion, the EB1 fraction and elaiophylin of S. hygroscopicus have potent antimicrobial, antifungal, and anticancer activities.

N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression.

BACKGROUND: Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells. METHODS: Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR. RESULTS: NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased. CONCLUSION: The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.

Synthesis and in vitro evaluation of (R), (S) and (R/S)-2-hexyne-1,4-diol, a natural product produced by fungus Clitocybe catinus, and related analogs as potential anticancer agents.

The search for natural products and related analogs as potential anticancer agents has seen a significant growth worldwide. Since small sized propargylic diols can be found in nature and chemically synthesized, their evaluation against cancer cells has been of great interest, being a topic of relevance to be investigated. For this purpose, a scalable approach aiming at the synthesis of several propargylic diols and their bioactivity against seven tumor cell lines were evaluated. Interestingly, when the compound 1a, a natural product produced by fungus Clitocybe catinus, was tested in its racemic mixture a more effective activity was observed if compared when enantiopure R-1a or S-1a were tested separately.

Cytotoxic activity of marine algae against cancerous cells

This paper presents an investigation on the cytotoxic activity in human tumor cell from dichloromethane, chloroform, methanol, ethanol, water extracts, and hexane and chloroform fractions from green, brown and red algae collected at Riacho Doce Beach, north coast of Alagoas, Brazil, against the cancer cells K562 (chronic myelocytic leukemia), HEp-2 (laryngeal epidermoid carcinoma) and NCI-H292 (human lung mucoepidermoid carcinoma) through the MTT colorimetric method. The dichloromethane extract and chloroform fraction of Hypnea musciformis showed the best cytotoxic activity against K562 (3.8±0.2 µg.mL-1 and 6.4±0.4 µg.mL-1, respectively). Dichloromethane extracts of Dictyota dichotoma (16.3±0.3 µg.mL-1) and the chloroform fraction of H. musciformis (6.0±0.03 µg.mL-1) and chloroform fraction of P. gymnospora (8.2±0.4) were more active against HEp-2 as well as ethanol extracts of P. gymnospora (15.9±2.8 µg.mL-1) and chloroform fraction of H. musciformis (15.0±1.3 µg.mL-1) against the cell NCI-H292. The constituents with higher anticancer action are present in the extracts of dichloromethane and chloroform and in the chloroform fraction of H. musciformis, Digenea simplex, P. gymnospora, and D.dichotoma. In the case of the seaweed S. vulgare, the anticancer constituents are present in the aqueous extract.

Antimicrobial, antiproliferative and proapoptotic activities of extract, fractions and isolated compounds from the stem of Erythroxylum caatingae plowman.

In the study, we have examined the antitumor and antimicrobial activities of the methanol extract, the fractions, a fraction of total alkaloids and two alkaloids isolated from the stem of Erythroxylum caatingae Plowman. All test fractions, except the hexane fractions, showed antimicrobial activity on gram-positive bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice was observed in these fractions and 6ß-Benzoyloxy-3α-(3,4,5- trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC-1 was used to verify the mechanism of action of the compounds of E. caatingae that showed cytotoxicity less than 30 µg/mL in leukemic cells. After 48 h of incubation, we observed that the acetate: methanol (95:5), acetate, and chloroform fractions, as well as the catuabine B, increased in the number of cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the mitochondrial membrane by incorporation of JC-1 showed that most cells during incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and 59.2%) were stained, suggesting the involvement of an intrinsic pathway of apoptosis.

Cytotoxic effect and apoptosis induction by Bothrops leucurus venom lectin on tumor cell lines.

Neoplastic transformation is the abnormal proliferation of cells. These transformations are often related to changes in cell surface glycoconjugates which can be detected by lectins. We evaluated the anti-tumor potential of BlL, a galactoside-binding lectin isolated from Bothrops leucurus venom as well as its cytotoxicity and hemolysis activity. The phosphatidylserine externalization and mitochondrial membrane potential were also determined. BlL exhibited cytotoxic activity against all tumor cell lines tested by induced phosphatidylserine externalization and mitochondrial depolarization, indicating cell death by apoptosis.

Cytotoxic, antitumor and leukocyte migration activities of resveratrol and sitosterol present in the hidroalcoholic extract of Cissus sicyoides L., Vitaceae, leaves

Cissus sicyoides L. pertains to the Vitaceae family. It is popularly known as "insulina, cipo-pucá, bejuco caro, puci, anil trepador". A vasoconstrictor effect and an antibacterial activity have also been allocated to it. In Brazil, C. sicyoides was evaluated for its anticonvulsant and anti-diabetc properties. Phytochemistry studies identified and isolated sitosterol and resveratrol compounds from its aerial parts which are pointed out as having antitumor activities. The goal of this study was to investigate the cytotoxic and antitumor activities of Cissus sicyoides hydroalcoholic extract as well as its ability to repair leukocytes cells to injured tissue. Cissus sicyoides did not demonstrate cytotoxic activity but showed an inhibition of tumor growth in face of the tumors tested. The extract had a strong chemotactic effect on the twenty four hours period after treatment. The hidroalchoolic extract of Cissus sicyoides presented antitumor activity which was prompted by T lymphocytes recruitment to the local lesion and suggests a new pathway to antitumor activity by activation of lymphoid lineage.

Cissus sicyoides pertence à família das Vitaceae. É conhecido popularmente como "insulina, cipó-puca, bejuco caro, puci, anil trepador". Esta planta apresenta efeito vasoconstritor eatividade antibacteriana. No Brasil, C. sicyoides foi avaliado pelas suas propriedades anticonvulsivante e anti-diabética. Estudos fitoquímicos identificaram e isolaram a partir de suas partes aéreas o sitoesterol e o resveratrol compostos que são apontados por apresentar atividade antitumoral. O objetivo deste estudo foi investigar as atividades citotóxica e antitumoral do extrato hidroalcoólico Cissus sicyoides bem como a sua capacidade de recrutar leucócitos para os tecidos lesados. Cissus sicyoides não demonstrou atividade citotóxica, mas apresentou uma inibição do crescimento tumoral frente aos tumores testados. O extrato teve um forte efeito quimiotático 24 h após o tratamento. O extrato hidroalcoólico de Cissus sicyoides apresentou atividade antitumoral, relacionada ao recrutamento de linfócitos T para o local da lesão sugerindo que esta atividade esteve relacionada à ativação da linhagem linfóide.

Atividade antimicrobiana de Lippia alba (Mill. ) N. E. Brown (Verbenaceae) / Antimicrobial activity of Lippia alba (Mill. ) N. E. Brown (Verbenaceae)

Lippia alba (Mill.) N. E. Brown (Verbenaceae), amplamente distribuída em todo o território brasileiro, é conhecida popularmente como erva cidreira e utilizada na medicina popular como analgésica, febrífuga, antiinflamatória, antigripal e nas afecções hepáticas. Extratos brutos foram preparados a partir de plantas cultivadas, de modo padronizado, em horta medicinal do Laboratório de Fitoterapia da Empresa Pernambucana de Pesquisa Agropecuária (IPA) para a verificação da atividade antimicrobiana, in vitro, pelo método de difusão em disco de papel. A concentração inibitória mínima (CIM) foi determinada para os extratos que exibiram melhores atividades. Os resultados obtidos mostraram que os extratos clorofórmico, acetônico e etanólico da raiz foram ativos frente a Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Mycobacterium smegmatis, Candida albicans e Monilia sitophila e os extratos hexânicos, etanólicos e metanólicos das folhas inibiram S. aureus, M. luteus, B. subtilis, M. smegmatis e M. sitophila. A menor concentração inibitória (CIM = 31,2 µg/mL), foi obtida para o extrato clorofórmico da raiz frente a B. subtilis e M. luteus.

Lippia alba (Mill.) N. E. Brown (Verbenaceae), commonly known as "erva cidreira", is widely distributed throughout Brazil and is used in folk medicine as an analgesic, anti-inflammatory, cold remedy, as well as to reduce fevers and treat hepatic afflictions. Crude extracts of L. alba were prepared from plants cultivated in the medicinal garden of the Laboratório de Fitoterapia of the Empresa Pernambucana de Pesquisa Agropecuária (IPA), State of Pernambuco, Brazil, using standard techniques to test their in vitro antibacterial activity using the paper disk-diffusion method. The minimum inhibitory concentration (MIC) was determined for those extracts demonstrating the highest activity. The results demonstrated that the chloroform, acetone and ethanol extracts of root material were active against the growth of Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Mycobacterium smegmatis, Candida albicans and Monilia sitophila, while the hexane, ethanol and methanol extracts of leaves inhibited the growth of S. aureus, M. luteus, B. subtilis, M. smegmatis and M. sitophila. The lowest inhibitory concentration (MIC = 31.2 µg/mL) was obtained with the chloroform root extract against B. subtilis and M. luteus.