scholarly journals Blue biotechnology – drugs from our o ceans

2010 ◽  
pp. 107-110
Author(s):  
Lekha Menon Margassery
Keyword(s):  
Fungal Infections ◽  
The Elderly ◽  
Blood Stream ◽  
New Drugs ◽  
Drug Resistant ◽  
Modern Life ◽  
Major Health ◽  
Transplant Patients ◽  
The Earth ◽  
Anti Fungal

Fungi are one of the major health concerns in modern life. It is known that up to 20% of patients with blood stream infections in intensive care units are affected by disease producing fungi such as Candida and Aspergillus, sometimes dominating the infections in doses that could be lethal. Patients who are immune-compromised/ immune-suppressed – including the elderly, HIV-infected patients, chemotherapy recipients, and transplant patients - are more prone to fungal infections. There are anti-fungal drugs available, but they are expensive and can have severe side effects such as nephrotoxicity (kidney damage). In addition, a major concern is that fungi such as Candida can become drug-resistant. Therefore there is a pressing need to identify new drugs to treat fungi and the diseases associated with them. Oceans cover about 70% of the earth and it is highly diverse in terms of its wealth – the marine organisms. It has been seen ...

Current Pharmaceutical Aspects of Synthetic Quinoline Derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Rukhsana Tabassum ◽  
Muhammad Ashfaq ◽  
Hiroyuki Oku
Keyword(s):  
Fungal Infections ◽  
Biological Activities ◽  
Chemical Properties ◽  
New Drugs ◽  
Quinoline Derivatives ◽  
Wide Range ◽  
Anti Cancer ◽  
Anti Fungal ◽  
Physical And Chemical ◽  
And Chemical Properties

Abstract:: Quinoline derivatives are considered as broad spectrum pharmacological compounds that exhibit wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications it is very popular compound to design new drugs for treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer’s disease and diabetes . In this review our major focus is to pay attention on biological activities of quinoline compounds in treatment of these diseases such as, anti-viral, anti-cancer, anti-malarial, anti-bacterial, anti-fungal, anti-tubercular and anti-diabetic.

Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents

1998 ◽  
Vol 9 (4) ◽  
pp. 480-497 ◽  
Author(s):  
H. Tsai ◽  
L.A. Bobek
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Artificial Saliva ◽  
Therapeutic Agents ◽  
Fungal Species ◽  
Drug Resistant ◽  
Opportunistic Fungi ◽  
Ergosterol Synthesis ◽  
Function Relationship ◽  
Anti Fungal

Histatins constitute a group of small, cationic multifunctional proteins present in the saliva of human and some nonhuman primates. The most significant function of histatins may be their anti-fungal activity against Candida albicans and Cryptococcus neoformans. Histatins have been extensively studied at both the protein and gene levels. The structure-function relationship of histatins with respect to their candidacidal activity has also been studied by means of recombinant histatin variants, as well as by chemically synthesized histatin fragments. The mechanism of histatins' action on Candida albicans is not clear, but it appears to be different from that of azole-based anti-fungal drugs which interrupt ergosterol synthesis. During the past 20 years, fungal infections have become more prevalent as a result of the emergence of AIDS, as well as, paradoxically, modern medical advances. The toxicity of current anti-fungal medicine, the emergence of drug-resistant strains, and the availability of only a few types of anti-fungal agents are the major disadvantages of current anti-fungal therapy. Therefore, the importance of the search for new, broad-spectrum anti-fungals with little or no toxicity cannot be overemphasized. The following properties make histatins promising anti-fungal therapeutic agents: (1) They have little or no toxicity; (2) they possess high cidal activities against azole-resistant fungal species and most of the fungal species tested; and (3) their candidacidal activity is similar to that of azole-based antifungals. Current research efforts focus on the development of improved histatins with enhanced cidal activity and stability, and of suitable and effective histatin delivery systems. These and other approaches may help to outpace the growing list of drug-resistant and opportunistic fungi causing life-threatening, disseminating diseases. The histatins with improved protective properties may also be used as components of artificial saliva for patients with salivary dysfunction.

Adoptive Immune Cell Therapy for the Control of Fungal Infections in Hematopoietic Stem Cell Transplant Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4358-4358
Author(s):  
Lung-Ji Chang ◽  
Yin Liang ◽  
Lily Lien ◽  
Chun- Rong Tong ◽  
Lu-Jia Dong ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Fungal Infections ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Immune Effector ◽  
Effector Cells ◽  
Transplant Patients ◽  
Fungal Antigens ◽  
Anti Fungal

Abstract Similar to virus infections, fungal infections are commonly seen in immunosuppressed transplant patients and can be life-threatening. Invasive Aspergillosis and Candidiasis are principal fungal infections among hematopoietic stem cell transplant (HSCT) patients, but Aspergillosis and other molds are the leading cause of deaths by fungal infections in immunocompromised allogeneic HSCT patients. The most effective treatment for fungal infections is preemptive and empirical anti-fungal therapies using agents such as fluconazole and amphotericin B deoxycholate (AmB-D). However, the success rate of antifungal therapy is generally low (in the 30–40% range) and associated with high toxicity. Both diagnosis and treatment for fungal infections are expensive and often ineffective. While improved formulations of AmB-D, second-generation triazoles, and echinocandins may be tolerable, newer generations of anti-fungal agents are very expensive. In animal studies, it has been shown that Aspergillosis can be successfully treated using Aspergillus-specific cytotoxic T cells (CTLs). Therefore, it is conceivable that CTLs specific to fungal antigens are effective in controlling fungal infections in allogeneic HSCT patients. To explore anti-fungal immune cell therapy, we used two different approaches to generate fungus-specific immune cells: Trichoderma and Rhizopus fungal lysates as antigen source to pulse dendritic cells (DCs), and pooled antigenic peptides to pulse DCs. The antigen-primed DCs were then co-cultured with lymphocytes to generate antigen-specific immune effector cells. The ex vivo generated anti-fungal immune cells displayed antigen-specific effector functions as illustrated by intracellular IFN-γ and CD107a staining. Interestingly, the fungus-specific immune effector cells are mostly CD4 T cells for all three species of fungal antigens. In a pilot clinical study, patients were selected when diagnosed with invasive aspergillosis based on galactomannan and beta-glucan assays, radiographs, CT scans, and/or blood cultures, or after an extended unsuccessful anti-fungal treatment with non-tolerable organ toxicity. Early indications suggest that the infusion of anti-fungal immune cells is safe, with therapeutic efficacy based on objective clinical evidence and importantly, is cost-effective. Nevertheless, more effective diagnosis and surveillance tools are needed to document the effectiveness of our anti-fungal immune cell treatment.

scholarly journals An Emerging Multi-Drug Resistant Yeast Like Fungus Candida auris Infections in ICUs

2020 ◽  
Vol 8 (02) ◽  
pp. 1-2
Author(s):  
Rajeshwar Reddy Kasarla
Keyword(s):  
Diabetes Mellitus ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Fungal Pathogens ◽  
Metabolic Disorders ◽  
Fungal Infections ◽  
Drug Resistant ◽  
Candida Auris ◽  
Anti Fungal ◽  
Transplantation Procedures

 The incidence of fungal infections in recent years is increasing rapidly and there is an emergence of newer fungal pathogens and anti-fungal drug resistance due to multiple predisposing reasons such as prolonged and indiscriminate use of antibiotic therapy, immunosuppressive corticosteroid therapy, aggressive use of ant-cancer drugs, bone marrow and organ transplantation procedures, and underlying conditions like immunodeficiency diseases (E.g., AIDS) and metabolic disorders such as diabetes mellitus.

scholarly journals The role and importance of fungal infections in intensive care units, ICU

2003 ◽  
Vol 56 (11-12) ◽  
pp. 537-541 ◽  
Author(s):  
Milanka Tatic ◽  
Danica Stanic-Canji ◽  
Biljana Draskovic ◽  
Aleksandar Komarcevic ◽  
Djordje Gajdobranski
Keyword(s):  
Intensive Care ◽  
Mortality Rate ◽  
Intensive Care Units ◽  
Fungal Infections ◽  
Clinical Manifestations ◽  
Blood Stream ◽  
Fungal Colonization ◽  
Transplant Patients ◽  
Tract Infections ◽  
Inadequate Nutrition

Introduction The incidence of fungal infections is constantly increasing, especially in Intensive Care Units (ICU). On the one hand ICU are places for treatment of most difficult, often immunodeficient patients, and on the other hand their treatment often requires invasive procedures, support of vital organs and adequate monitoring. Epidemiology In approximately 78% of patients the cause of infection are Candida species with mortality rate of 57%. Less common causative agents are Aspergillus species, but with very high mortality rate of up to 100%. Pathogenesis Candida albicans is a normal inhabitant of the oropharingeal and digestive systems. Hospitalization, trauma, loss of immunity and use of strong antibiotics facilitate fungal colonization. Inadequate nutrition, poor perfusion, ischemia and corticosteroids therapy lead to damage of intestinal mucosa. Combined with improper production of IG A, it predisposes to translocation of fungi through mucosa and invasion of the blood stream. Clinical manifestations Most common forms are urinary tract infections, intraabdominal candidiasis, disseminated candidiasis and candidemia. Diagnosis Diagnosis of fungal infections is very difficult. It is based on clinical picture, microbiological, histological, radiological, serologic and molecular examinations. Treatment Treatment is usually based on systemic antimycotic agents (Amphotericin B, Azoles: Fluconazole, Flucytosine). Prophylactic treatment is still a matter of debate. It is not routinely recommended in ICU, but is commonly used in transplant patients.

Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery

2017 ◽  
Vol 17 (19) ◽  
pp. 2129-2142 ◽  
Author(s):  
Renata Płocinska ◽  
Malgorzata Korycka-Machala ◽  
Przemyslaw Plocinski ◽  
Jaroslaw Dziadek
Keyword(s):  
Drug Resistance ◽  
Dna Replication ◽  
Drug Targets ◽  
Rapid Development ◽  
New Drugs ◽  
Drug Resistant ◽  
Antituberculosis Drug ◽  
Nucleotide Synthesis ◽  
Antituberculosis Therapy ◽  
Optimal Drug

Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and the search for optimal drug targets are top priority areas of tuberculosis research. Factors: Key characteristics of mycobacteria include: slow growth, the ability to transform into a metabolically silent - latent state, intrinsic drug resistance and the relatively rapid development of acquired drug resistance. These factors make finding an ideal antituberculosis drug enormously challenging, even if it is designed to treat drug sensitive tuberculosis strains. A vast majority of canonical antibiotics including antituberculosis agents target bacterial cell wall biosynthesis or DNA/RNA processing. Novel therapeutic approaches are being tested to target mycobacterial cell division, twocomponent regulatory factors, lipid synthesis and the transition between the latent and actively growing states. Discussion and Conclusion: This review discusses the choice of cellular targets for an antituberculosis therapy, describes putative drug targets evaluated in the recent literature and summarizes potential candidates under clinical and pre-clinical development. We focus on the key cellular process of DNA replication, as a prominent target for future antituberculosis therapy. We describe two main pathways: the biosynthesis of nucleic acids precursors – the nucleotides, and the synthesis of DNA molecules. We summarize data regarding replication associated proteins that are critical for nucleotide synthesis, initiation, unwinding and elongation of the DNA during the replication process. They are pivotal processes required for successful multiplication of the bacterial cells and hence they are extensively investigated for the development of antituberculosis drugs. Finally, we summarize the most potent inhibitors of DNA synthesis and provide an up to date report on their status in the clinical trials.

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 A Pharmacological Analysis of the Activity and Failure of the Medical Treatment of High-Grade Osteosarcoma

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 141
Author(s):  
Alessandro Comandone ◽  
Antonella Boglione ◽  
Tiziana Comandone ◽  
Fausto Petrelli
Keyword(s):  
Bone Cells ◽  
Age Groups ◽  
The Elderly ◽  
New Drugs ◽  
High Grade ◽  
Secondary Resistance ◽  
Orthopedic Surgeons ◽  
Close Cooperation ◽  
High Grade Osteosarcoma ◽  
Effective Drugs

Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.

scholarly journals Herbal Products and Their Active Constituents Used Alone and in Combination with Antifungal Drugs against Drug-Resistant Candida sp.

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 655
Author(s):  
Anna Herman ◽  
Andrzej Przemysław Herman
Keyword(s):  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Membrane Transporters ◽  
Drug Resistant ◽  
Herbal Products ◽  
Active Constituents ◽  
Over Expression ◽  
Candida Sp ◽  
Current State

Clinical isolates of Candida yeast are the most common cause of opportunistic fungal infections resistant to certain antifungal drugs. Therefore, it is necessary to detect more effective antifungal agents that would be successful in overcoming such infections. Among them are some herbal products and their active constituents.The purpose of this review is to summarize the current state of knowledge onherbal products and their active constituents havingantifungal activity against drug-resistant Candida sp. used alone and in combination with antifungal drugs.The possible mechanisms of their action on drug-resistant Candida sp. including (1) inhibition of budding yeast transformation into hyphae; (2) inhibition of biofilm formation; (3) inhibition of cell wall or cytoplasmic membrane biosynthesis; (4) ROS production; and (5) over-expression of membrane transporters will be also described.

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