scholarly journals Resistance mechanisms of Cryptococcus spp. and plant compounds as tools to combat them

2021 ◽  
Vol 10 (2) ◽  
pp. e57810212819
Author(s):  
Suéllen Pedrosa da Silva ◽  
Clarice Barbosa Lucena da Costa ◽  
José Dayvid Ferreira da Silva ◽  
Robson Raion de Vasconcelos Alves ◽  
Guilherme Antonio de Souza Silva ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Public Health Problem ◽  
Antimicrobial Activities ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Fungal Resistance ◽  
Ergosterol Synthesis ◽  
Cryptococcus Spp ◽  
Etiological Agents ◽  
Basidiomycete Fungi

Cryptococcus is a genus of dimorphic basidiomycete fungi found in the form of yeasts and filaments. Cryptococcosis has as main etiological agents the species Cryptococcus neoformans and Cryptococcus gattii. This disease is considered a public health problem and has becoming more alarming because of the limitations of antimicrobials available to its treatment, in addition to an increase in reports of fungal resistance. In this sense, the present review sought to survey information on the resistance mechanisms of Cryptococcus spp. against the main drugs used in cryptococcosis therapy as well as on the antimicrobial activities of plants against these fungi. Studies have reported that several mechanisms may be involved in fungal resistance to drugs including drug inactivation by enzymes, expression of efflux pumps and others drug transporters, as well as changes in the drug target and/or implementation of alternative metabolic pathways. As an alternative to conventional antimicrobials, substances and molecules extracted from plants have demonstrated potential for controlling these pathogens. These phytochemicals can trigger the inhibition and/or death of Cryptococcus through morphological changes on fungi cells, inhibition of ergosterol synthesis, cell leakage, capsular decrease, interference in cell division, reduction of activity of several enzymes such as laccase and urease, inhibition of biofilm formation, among others. In this sense, plants are an important source of bioactive compounds with antimicrobial activity that can be studied in the search for new drugs that are increasingly effective, specific and less toxic in the control of cryptococcosis.

scholarly journals Green propolis as an adjuvant against nontuberculous mycobacteria

Rodriguésia ◽  
2021 ◽  
Vol 72 ◽  
Author(s):  
Suzane Olachea Allend ◽  
Lisiane Volcão ◽  
Carolina da Silva Canielles ◽  
Israel Barbosa ◽  
Dara Biatobock ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Nontuberculous Mycobacteria ◽  
Ethanol Extract ◽  
Antimycobacterial Activity ◽  
Antimicrobial Activities ◽  
Resistance Mechanisms ◽  
The Other ◽  
New Drugs ◽  
Mycobacterium Chelonae

Abstract Natural products have been touted as important tools because of their vast potential for the development of compounds with antimicrobial activity and the possible inhibitory activity and/or adjuvant resistance mechanisms. Propolis has been empirically used for many years for the treatment of diseases, mainly due to its antioxidant, anti inflammatory and antimicrobial activities. This study aimed to evaluate the in vitro antimycobacterial activity of the ethanol extract of propolis alone and in combination with rifampicin (RIF), amikacin (AMI) and ciprofloxacin (CIP). The ethanol extract of propolis showed antibacterial activity against Mycobacterium chelonae and M. kansasii and was capable of increasing AMI, RIF and CIP activity in combination. On the other hand, compared to M. absecessus, M. fortuitum and M. avium, the extract was not active at 200 µg/mL and did not show pronounced adjuvant capacity when evaluated in association with the drugs. Based on these results, it can be concluded that the ethanol extract of propolis could be an alternative in the development of new drugs and can be used complementary with the current mycobacteriosis treatment.

4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB

2019 ◽  
Vol 19 (8) ◽  
pp. 567-578 ◽  
Author(s):  
Marcus Vinicius Nora de Souza ◽  
Thais Cristina Mendonça Nogueira
Keyword(s):  
Treatment Time ◽  
Public Health Problem ◽  
New Drugs ◽  
Global Public Health ◽  
Synthesis Mechanism ◽  
Highly Active ◽  
Latent Disease ◽  
Resistant Strains ◽  
Chemical Class ◽  
Global Public Health Problem

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

Recent Status and Advancements in the Development of Antifungal Agents: Highlights on Plant and Marine Based Antifungals

2019 ◽  
Vol 19 (10) ◽  
pp. 812-830 ◽  
Author(s):  
P. Marie Arockianathan ◽  
Monika Mishra ◽  
Rituraj Niranjan
Keyword(s):  
Cell Wall ◽  
Antifungal Agents ◽  
Fungal Diseases ◽  
Fungal Cell Wall ◽  
Fungal Resistance ◽  
Ergosterol Biosynthesis ◽  
Fungal Cell ◽  
Ergosterol Synthesis ◽  
Glucan Synthesis ◽  
Anti Fungal

The developing resistance in fungi has become a key challenge, which is being faced nowadays with the available antifungal agents in the market. Further search for novel compounds from different sources has been explored to meet this problem. The current review describes and highlights recent advancement in the antifungal drug aspects from plant and marine based sources. The current available antifungal agents act on specific targets on the fungal cell wall, like ergosterol synthesis, chitin biosynthesis, sphingolipid synthesis, glucan synthesis etc. We discuss some of the important anti-fungal agents like azole, polyene and allylamine classes that inhibit the ergosterol biosynthesis. Echinocandins inhibit β-1, 3 glucan synthesis in the fungal cell wall. The antifungals poloxins and nikkomycins inhibit fungal cell wall component chitin. Apart from these classes of drugs, several combinatorial therapies have been carried out to treat diseases due to fungal resistance. Recently, many antifungal agents derived from plant and marine sources showed potent activity. The renewed interest in plant and marine derived compounds for the fungal diseases created a new way to treat these resistant strains which are evident from the numerous literature publications in the recent years. Moreover, the compounds derived from both plant and marine sources showed promising results against fungal diseases. Altogether, this review article discusses the current antifungal agents and highlights the plant and marine based compounds as a potential promising antifungal agents.

scholarly journals Thiourea and Guanidine Compounds and their Iridium Complexes in Drug-Resistant Cancer Cell Lines: Structure-Activity Relationships and Direct Luminescent Imaging

2019 ◽  
Author(s):  
Samuel J. Thomas ◽  
Barbora Balonova ◽  
Jindrich Cinatl ◽  
Mark Wass ◽  
Christopher Serpell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Nature Medicine ◽  
Cancer Cell Lines ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Iridium Complexes ◽  
Safety Issues ◽  
Structure Activity Relationships ◽  
Structure Activity

<p>Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. We have systematically synthesised a set of thiourea compounds and their guanidine analogues, and elucidated structure-activity relationships in terms of cellular toxicity in three ovarian cancer cell lines and their cisplatin-resistant sub-lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea- and guanidine-based materials.</p>

Sterol 14α-Demethylase from Trypanosomatidae Parasites as a Promising Target for Designing New Antiparasitic Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Paulo Fernando da Silva Santos-Júnior ◽  
Martine Schmitt ◽  
João Xavier de Araújo-Júnior ◽  
Edeildo Ferreira da Silva-Júnior
Keyword(s):  
Combined Therapy ◽  
Experimental Studies ◽  
New Drugs ◽  
Host Cells ◽  
Sar Studies ◽  
Promising Target ◽  
Ic50 Value ◽  
Leishmania Spp ◽  
Etiological Agents ◽  
Antiparasitic Agents

: Trypanosomatidae family belongs to the Kinetoplastida order, which consists of obligatory parasites that affect plants and all classes of vertebrates, especially humans and insects. Among the heteroxenic parasites, Leishmania spp., Trypanosoma cruzi, and T. brucei are protozoa of most significant interest for medicinal chemistry, being etiological agents of Leishmaniasis, Chagas, and Sleep Sickness diseases, respectively. Currently, inefficient pharmacotherapy, especially in chronic phases and low selectivity towards parasite/host cells, justifies the need to discover new drugs to treat them effectively. Among other targets, the sterol 14α-demethylase (CYP51), an enzyme responsible for ergosterol's biosynthesis in Trypanosomatidae parasites, has received more attention in the development of new bioactive compounds. In this context, antifungal ravuconazole proved to be the most promising drug among this class against T. cruzi, being used in combined therapy with Bnz in clinic trials. Non-antifungal inhibitors, such as VFV and VNF, have shown promising results against T. cruzi and T.brucei, respectively, being tested in Bnz-combined therapies. Among the experimental studies involving azoles, compound (15) was found to be the most promising derivative, displaying an IC50 value of 0.002 µM against amastigotes from T. cruzi, in addition to being non-toxic and highly selective towards TcCYP51 (< 25 nM). Interestingly, imidazole analog (16) was active against infectious forms of these three parasites, demonstrating Ki values of 0.17, 0.02, and 0.36 nM for CYP51 from T. cruzi, T. brucei, and L. infantum. Finally, this review will address promising inhibitors targeting sterol 14α-demethylase (CYP51) from Trypanosomatidae parasites, highlighting SAR studies, interactions with this target, and recent contributions and advances in the field, as well.

Respiratory infections caused by Haemophilus influenzae β-lactamase positive carrying blaTEM gene

2020 ◽  
Vol 30 (Supplement_2) ◽  
Author(s):  
J Valério ◽  
H Ferreira ◽  
C Chaves ◽  
F Rodrigues ◽  
N Osório
Keyword(s):  
Antibiotic Therapy ◽  
Respiratory Infections ◽  
Clinical Pathology ◽  
Resistance Mechanisms ◽  
Important Data ◽  
Ampicillin Resistance ◽  
Phenotypic Profile ◽  
Antimicrobial Susceptibility Profile ◽  
Activity Screening ◽  
Etiological Agents

Abstract Introduction One of the main etiological agents of respiratory infections is H. Influenzae. The group of antibiotics most used to the treatment of H. influenzae infections is β-lactams. The most common β-lactam resistance is to ampicillin, characterized by the production of TEM (95%) and ROB (5%) β-lactamases, designated enzymatic resistance. Objectives Characterize the susceptibility profile of H. influenzae to β-lactam antibiotics, to evaluate the enzymatic resistance by the β-lactamase production and to correlate the phenotypic profile with the presence of the blaTEM. Methodology Total of 152 isolates of H. influenzae from respiratory infections were evaluated: 88 from expectorations, 56 from bronchial aspirates and 8 from bronchoalveolar lavage, collected in Clinical Pathology Service of Centro Hospitalar e Universitário de Coimbra. The results of the antimicrobial susceptibility profile and the β-lactamase screening were also provided. In order to investigate the blaTEM, DNA was extracted from the isolates and the detection was performed using the PCR technique. Results The prevalence of the blaTEM in the isolates was 31.6%, of these 33.3% showed resistance to ampicillin and 57.9% were positive in β-lactamase activity screening and blaTEM carriers. There was a statistically significance between the presence of the gene with ampicillin resistance and β-lactamase activity screening. Conclusion β-lactamase TEM production was the main mechanism of enzymatic resistance which demonstrates the high spread of the blaTEM among isolates of H. influenzae. The results found suggest that the negative strains for this β-lactamase but that presented β-lactamases with activity and resistance to β-lactams should have other β-lactamases as ROB or others. However strains with β-lactamase negative should have other mechanisms promoting the resistance as PBP3. This study provides important data on the antibiotic therapy, to minimize the expression of resistance mechanisms and problems associated with treatment.

scholarly journals Inhibitory Spectra and Modes of Antimicrobial Action of Gallotannins from Mango Kernels (Mangifera indicaL.)

2011 ◽  
Vol 77 (7) ◽  
pp. 2215-2223 ◽  
Author(s):  
Christina Engels ◽  
Andreas Schieber ◽  
Michael G. Gänzle
Keyword(s):  
Staphylococcus Aureus ◽  
Wild Type Strain ◽  
Antimicrobial Activities ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Wild Type ◽  
Gram Positive Bacteria ◽  
Food Borne ◽  
Membrane Bound ◽  
Bacteria And Fungi

ABSTRACTThis study investigated the antimicrobial activities and modes of action of penta-, hexa-, hepta-, octa-, nona-, and deca-O-galloylglucose (gallotannins) isolated from mango kernels. The MICs and minimum bactericidal concentrations (MBCs) against food-borne bacteria and fungi were determined using a critical dilution assay. Gram-positive bacteria were generally more susceptible to gallotannins than were Gram-negative bacteria. The MICs of gallotannins againstBacillus subtilis,Bacillus cereus,Clostridium botulinum,Campylobacter jejuni,Listeria monocytogenes, andStaphylococcus aureuswere 0.2 g liter−1or less; enterotoxigenicEscherichia coliandSalmonella entericawere inhibited by 0.5 to 1 g liter−1, and lactic acid bacteria were resistant. The use of lipopolysaccharide mutants ofS. entericaindicated that the outer membrane confers resistance toward gallotannins. Supplementation of LB medium with iron eliminated the inhibitory activity of gallotannins againstStaphylococcus aureus, and siderophore-deficient mutants ofS. entericawere less resistant toward gallotannins than was the wild-type strain. Hepta-O-galloylglucose sensitizedLactobacillus plantarumTMW1.460 to hop extract, indicating inactivation of hop resistance mechanisms, e.g., the multidrug resistance (MDR) transporter HorA. Carbohydrate metabolism ofLactococcus lactisMG1363, a conditionally respiring organism, was influenced by hepta-O-galloylglucose when grown under aerobic conditions and in the presence of heme but not under anaerobic conditions, indicating that gallotannins influence the respiratory chain. In conclusion, the inhibitory activities of gallotannins are attributable to their strong affinity for iron and likely additionally relate to the inactivation of membrane-bound proteins.

scholarly journals Solution Structures and Dynamic Assembly of the 24-Meric Plasmodial Pdx1–Pdx2 Complex

2020 ◽  
Vol 21 (17) ◽  
pp. 5971
Author(s):  
Najeeb Ullah ◽  
Hina Andaleeb ◽  
Celestin Nzanzu Mudogo ◽  
Sven Falke ◽  
Christian Betzel ◽  
...  
Keyword(s):  
Drug Targets ◽  
Pyridoxal Phosphate ◽  
Plasmodium Species ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Enzyme Complex ◽  
Solution Structures ◽  
Dynamic Assembly ◽  
Bioanalytical Techniques ◽  
Initial Drug

Plasmodium species are protozoan parasites causing the deadly malaria disease. They have developed effective resistance mechanisms against most antimalarial medication, causing an urgent need to identify new antimalarial drug targets. Ideally, new drugs would be generated to specifically target the parasite with minimal or no toxicity to humans, requiring these drug targets to be distinctly different from the host’s metabolic processes or even absent in the host. In this context, the essential presence of vitamin B6 biosynthesis enzymes in Plasmodium, the pyridoxal phosphate (PLP) biosynthesis enzyme complex, and its absence in humans is recognized as a potential drug target. To characterize the PLP enzyme complex in terms of initial drug discovery investigations, we performed structural analysis of the Plasmodium vivax PLP synthase domain (Pdx1), glutaminase domain (Pdx2), and Pdx1–Pdx2 (Pdx) complex (PLP synthase complex) by utilizing complementary bioanalytical techniques, such as dynamic light scattering (DLS), X-ray solution scattering (SAXS), and electron microscopy (EM). Our investigations revealed a dodecameric Pdx1 and a monodispersed Pdx complex. Pdx2 was identified in monomeric and in different oligomeric states in solution. Interestingly, mixing oligomeric and polydisperse Pdx2 with dodecameric monodisperse Pdx1 resulted in a monodispersed Pdx complex. SAXS measurements revealed the low-resolution dodecameric structure of Pdx1, different oligomeric structures for Pdx2, and a ring-shaped dodecameric Pdx1 decorated with Pdx2, forming a heteromeric 24-meric Pdx complex.

scholarly journals Clerodendrum inerme (L.) Gaertn. Extract Exerts Anticancer Activity on Lung Cancer Cells

2018 ◽  
Vol 17 (2) ◽  
pp. 191-196
Author(s):  
Mahendra Kumar Chouhan ◽  
Pramod Jayadevappa Hurakadle ◽  
Harsha Vasudev Hegde
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Morphological Changes ◽  
New Drugs ◽  
Lung Cancer Cells ◽  
Lung Cancer Cell ◽  
Standard Drug ◽  
Efficient Treatment ◽  
Hydroalcoholic Extract ◽  
Antitumor Properties

Cancer is the leading cause of death word wide. Recently there are no new drugs for safe and efficient treatment. Clerodendrum inerme (L.) Gaertn. (Verbenaceae) plant is being used by the ethnic people for cancer treatment. In this study, cytotoxic and antiproliferative potential of hydroalcoholic (methanol and water; 70:30 v/v) extract of C. inerme were evaluated. Various anticancer investigations performed like, lung cancer cell A-549 culture, dye exclusion assay, MTT assay, morphological changes and compatibility with RBC, confirmed the presence of the moiety that have the cytotoxic and antiproliferative potential. Compatibility with RBC was observed, when treated with standard drug doxorubicin, and hydroalcoholic extract of C. inerme at 259.5 μg/ml concentration (IC50). In addition, the same treatment reveled, decrease in cytotoxic efficacy and cell viability against lung cancer cells. Furthermore, change in the cell morphology also suggesting potent antitumor properties of C. inerme. Dhaka Univ. J. Pharm. Sci. 17(2): 191-196, 2018 (December)

scholarly journals Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 715
Author(s):  
Julia Bespyatykh ◽  
Dmitry Bespiatykh ◽  
Maja Malakhova ◽  
Ksenia Klimina ◽  
Andrey Bespyatykh ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Resistance ◽  
Morphological Changes ◽  
Cell Structure ◽  
Model Organism ◽  
Good Alternative ◽  
Acid Group ◽  
New Drugs ◽  
Antituberculosis Drugs ◽  
Aureolic Acid

Mycobacterium tuberculosis is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, antibiotics of the aureolic acid group were tested on a model organism Mycobacterium smegmatis. We presumed that antibiotics of this group may be potential G4 ligands. However, this was not confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed morphological changes in the cell structure upon treatment. Transcriptomic analysis documented increased expression of MSMEG_3743/soj and MSMEG_4228/ftsW, involved in cell division. Therefore, drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a septum. Additionally, a decrease in the transcription level of several indispensable genes, such as nitrate reductase subunits (MSMEG_5137/narI and MSMEG_5139/narX) and MSMEG_3205/hisD was shown. We concluded that the mechanism of action of aureolic acid and its related compounds may be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs.

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