Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species

2019 ◽  
Vol 18 (27) ◽  
pp. 2338-2346 ◽  
Author(s):  
Eduardo Seiji Yamamoto ◽  
Jéssica Adriana Jesus ◽  
Adriana Bezerra-Souza ◽  
Márcia Dalastra Laurenti ◽  
Susan Pereira Ribeiro ◽  
...  
Keyword(s):  
New World ◽  
Parasite Species ◽  
Cutaneous Lesion ◽  
Leishmania Species ◽  
Health Condition ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Leishmanicidal Activity ◽  
Line Drug

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis.

scholarly journals In vitro interaction between paromomycin sulphate and four drugs with leishmanicidal activity against three New World Leishmania species

2013 ◽  
Vol 69 (1) ◽  
pp. 150-154 ◽  
Author(s):  
E. de Morais-Teixeira ◽  
M. K. Gallupo ◽  
L. F. Rodrigues ◽  
A. J. Romanha ◽  
A. Rabello
Keyword(s):  
New World ◽  
Leishmania Species ◽  
Leishmanicidal Activity ◽  
In Vitro Interaction

scholarly journals Ethnopharmacology Study of Plants from Atlantic Forest with Leishmanicidal Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Beatriz Mendes Santos ◽  
Adriana Bezerra-Souza ◽  
Sonia Aragaki ◽  
Eliana Rodrigues ◽  
Eric Umehara ◽  
...  
Keyword(s):  
Atlantic Forest ◽  
Skin Diseases ◽  
Common Knowledge ◽  
Health Condition ◽  
New Drugs ◽  
Cutaneous Lesions ◽  
Vegetative Organs ◽  
New Information ◽  
Hexane Extracts

Leishmaniasis is an infectious disease caused by a protozoan belonging toLeishmaniagenus. Different clinical outcomes can be observed depending on the parasite species and patient’s health condition. The outcomes can range from single cutaneous lesions to lethal visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and, in some cases, the second-line drug, amphotericin B, is used. Beside the toxicity of both classes of drugs, in some areas of the world, parasites are resistant to antimonial. These detrimental features make fundamental the discovery and characterization of new drugs or plant extracts with leishmanicidal effects. Brazil is a well-known country for its biodiversity. Additionally, the common knowledge inherited for generations in small villages makes Brazil a source of new information and resources for the discovery and development of new drugs. Based on ethnopharmacology, elderlies were interviewed about plants they commonly used for skin diseases and infections. Five native plants from Atlantic forest were indicated; EtOH andn-hexane extracts were prepared with the vegetative organs of the plants and assayed against promastigote and amastigote forms ofL. (L.) amazonensis. The major molecules of each extract were detected using qualitative nuclear magnetic resonance. Among all tested extracts, then-hexane extract from the leave ofEugenia uniflora(Myrtaceae), enriched in myricitrin and quercitrin flavonoids, was the most effective againstL. (L.) amazonensisamastigotes. This data supports the ethnopharmacology approach as a successful tool for the discovery of new drugs with leishmanicidal effects.

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

scholarly journals Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3523
Author(s):  
Wancheng Guo ◽  
Haiqin Wang ◽  
Peng Chen ◽  
Xiaokai Shen ◽  
Boxin Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Stem Cell ◽  
New Drugs ◽  
Cell Therapies ◽  
High Relapse Rate ◽  
High Incidence ◽  
Poorly Differentiated ◽  
Identification And Characterization

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

scholarly journals Antiangiogenic potential of Jatropha curcas latex in the chick chorioallantoic membrane model

2019 ◽  
Vol 29 (1) ◽  
pp. 32157
Author(s):  
Luciane Madureira Almeida ◽  
Elisa Flávia Luiz Cardoso Bailão ◽  
Illana Reis Pereira ◽  
Fabrício Alves Ferreira ◽  
Patrícia Lima D'Abadia ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Jatropha Curcas ◽  
Physicochemical Characterization ◽  
Chorioallantoic Membrane ◽  
Angiogenesis Inhibitor ◽  
Negative Control ◽  
New Drugs ◽  
Membrane Model ◽  
Chick Chorioallantoic Membrane

AIMS: To perform a physicochemical and phytochemical characterization of Jatropha curcas latex and to investigate its antiangiogenic potential. METHODS: We performed an initial physicochemical characterization of J. curcas latex using thermal gravimetric analyses and Fourier Transform Infrared spectroscopy. After that, phenols, tannins and flavonoids were quantified. Finally, the potential of J. curcas latex to inhibit angiogenesis was evaluated using the chick chorioallantoic membrane model. Five groups of 20 fertilized chicken eggs each had the chorioallantoic membrane exposed to the following solutions: (1) water, negative control; (2) dexamethasone, angiogenesis inhibitor; (3) Regederm®, positive control; (4) 25% J. curcas latex diluted in water; (5) 50% J. curcas latex diluted in water; and (6) J. curcas crude latex. Analysis of the newly-formed vascular net was made through captured images and quantification of the number of pixels. Histological analyses were performed to evaluate the inflammation, neovascularization, and hyperemia parameters. The results were statically analyzed with a significance level set at p ˂0.05.RESULTS: Physicochemical characterization showed that J. curcas latex presented a low amount of cis-1.4-polyisoprene, which reduced its elasticity and thermal stability. Phytochemical analyses of J. curcas latex identified a substantial amount of phenols, tannins, and flavonoids (51.9%, 11.8%, and 0.07% respectively). Using a chick chorioallantoic membrane assay, we demonstrated the antiangiogenic potential of J. curcas latex. The latex induced a decrease in the vascularization of the membranes when compared with neutral and positive controls (water and Regederm®). However, when compared with the negative control (dexamethasone), higher J. curcas latex concentrations showed no significant differences.CONCLUSIONS: J. curcas latex showed low thermal stability, and consisted of phenols, tannins, and flavonoids, but little or no rubber. Moreover, this latex demonstrated a significant antiangiogenic activity on a chick chorioallantoic membrane model. The combination of antimutagenic, cytotoxic, antioxidant and antiangiogenic properties makes J. curcas latex a potential target for the development of new drugs.

scholarly journals Characterization of bacteriocin and chitinase producing bacterial isolates with broad-spectrum antimicrobial activities

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Muhammad Yasir ◽  
Basit Zeshan ◽  
Nur Hardy A. Daud ◽  
Izzah Shahid ◽  
Hafza Khalid
Keyword(s):  
Antimicrobial Activity ◽  
Inhibitory Activity ◽  
Antifungal Drugs ◽  
Proteinase K ◽  
Diffusion Method ◽  
List Type ◽  
Bacterial Isolates ◽  
E Coli ◽  
Inhibitory Potential

Abstract There is a need for more efficient and eco-friendly approaches to overcome increasing microbial infections. Bacteriocins and chitinases from Bacillus spp. can be powerful alternatives to conventional antibiotics and antifungal drugs, respectively. The purpose of this study was to assess the inhibitory potential of bacteriocins and chitinase enzymes against multiple resistant bacterial and fungal pathogens. Bacterial isolates were selected by growth on minimal salts medium and after that were morphologically and biochemically characterized. The physiochemical characterization of bacteriocins was carried out. The inhibitory potential of bacteriocins towards six pathogenic bacteria was determined by the well diffusion assay while chitinase activity towards three fungal strains was determined by the dual plate culture assay. Two bacterial strains (WW2P1 and WRE4P2), out of nine showed inhibition of K. pneumonia, P. aeruginosa, E. coli and MRSA while WW4P2 was positive against S. typhimurium and E. coli and WRE10P2 against P. aeruginosa, S. pneumoniae. Two bacterial isolates (WW3P1 and WRE10P2) were chosen for further study on the basis of their antifungal activities. Of these, WW3P1 isolate was more effective against A. fumigatus as well as A. niger. The proteinaceous nature of the bacteriocins was confirmed by treatment of the crude extract with proteinase K. It was found that the inhibitory activity of strain WW3P1 against E. coli was highest at 20 °C, and against S. pneumoniae it was at 20 °C and pH 10 after treatment with EDTA. Inhibition by strain the WRE10P2 against P. aeruginosa was highest at 20 °C and pH 14. It was found that EDTA increased the inhibitory activity of strain WW2P1 against P. aeruginosa, K. pneumoniae and E. coli by 2 ± 0.235, 3.5 ± 0.288, 2.5 ± 1.040 times, respectively, of strain WRE4P2 against P. aeruginosa and E. coli by 2.5 ± 0.763, 2.7 ± 0.5 times, respectively, and of strain WRE10P2 against S. pneumoniae by 3 ± 0.6236 times. The isolates have promising inhibitory activity, which should be further analyzed for the commercial production of antimicrobials. Article highlights The current study aimed to isolate the microbiome from wheat plant (Triticum aestivum L.), to screen for bacteriocin production and to assess its antimicrobial activity against human pathogens. Forty-one phenotypically different bacterial colonies were subjected to bacteriocin purification from which 25 colonies showed positive reactions. These 25 bacterial isolates were screened against six different human bacterial pathogens using the well diffusion method to check the antimicrobial activity. Out of nine bacterial isolates, WW3P1 and WRE10P2 were able to degrade the chitin and utilize it as their sole energy source. Strain WRE4P2 exhibited partial inactivation in its activity against MRSA after treatment with proteinase K.

scholarly journals The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

2011 ◽  
Vol 106 (4) ◽  
pp. 475-478 ◽  
Author(s):  
Eliane de Morais-Teixeira ◽  
Quesia Souza Damasceno ◽  
Mariana Kolos Galuppo ◽  
Alvaro José Romanha ◽  
Ana Rabello
Keyword(s):  
Leishmania Species ◽  
Leishmanicidal Activity
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