A5029853082- Amoebic Infections and Treatments
- Legionella and Acanthamoeba research
- Parasitic Infections and Diagnostics
- Heme Oxygenase-1 and Carbon Monoxide
- Diagnosis and treatment of tuberculosis
- Parasites and Host Interactions
- Research on Leishmaniasis Studies
- Antibiotic Resistance in Bacteria
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pancreatitis Pathology and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Metal-Catalyzed Oxygenation Mechanisms
- Vibrio bacteria research studies
- Redox biology and oxidative stress
- Veterinary medicine and infectious diseases
- Enzyme function and inhibition
- Trypanosoma species research and implications
- Viral gastroenteritis research and epidemiology
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- Helminth infection and control
- Parasitic infections in humans and animals
- Coccidia and coccidiosis research
Center for Discovery
2013-2024
University of California, San Diego
2015-2024
National Institute of Pharmaceutical Education and Research
2024
University of Montana
2014-2023
Universidade Estadual Paulista (Unesp)
2020
Bangur Institute of Neurosciences
2016
Institute of Post Graduate Medical Education and Research
2016
University of California, San Francisco
2006-2014
Indian Council of Medical Research
2005
National Institute of Cholera and Enteric Diseases
1998-2004
Giardiasis is one of the most common causes diarrheal disease worldwide. Treatment primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up 20% cases, making development alternative antigiardials an important goal. To this end, we have screened a chemical library 746 approved human drugs 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 that caused...
Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), albendazole used in control programs for these diseases, but mainly effective against the microfilarial stage have minimal no effect on adult worms. Adult Onchocerca volvulus Brugia malayi worms (macrofilariae) live up 15 years, reproducing allowing infection persist a population. Therefore,...
Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for treatment of giardiasis amebiasis, with metronidazole 1 being most commonly used drug worldwide. However, failures in occur up to 20% cases development resistance is concern. We have re-examined 'old' nitroimidazoles as foundation systematic next-generation derivatives. Using this approach, derivatisation...
ABSTRACT Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri . The drug of choice in treating PAM antifungal antibiotic amphotericin B, but its use associated with severe adverse effects. Moreover, few patients treated B have survived PAM. Therefore, fast-acting and efficient drugs are urgently needed for treatment To facilitate screening this pathogen, an automated, high-throughput methodology was developed validated...
It has been 50 years since the first case of primary amoebic meningoencephalitis (PAM), an acute and rapidly fatal disease central nervous system (CNS), was reported in Australia. is now known that aetiological agent PAM Naegleria fowleri, amoeba commonly as 'the brain-eating amoeba'. N. fowleri infects humans different ages who are contact with water contaminated this micro-organism. distributed worldwide found growing bodies freshwater tropical subtropical environments. The number cases...
Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites bacteria reported, improved second-generation analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way efficiently assemble new libraries of analogues. Several metronidazole-triazole conjugates (Mtz-triazoles) have identified with excellent broad...
Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM particularly devastating infection. In absence economic inducements to invest development anti-PAM drugs pharmaceutical industry, drug discovery largely relies on 'repurposing'—a cost effective strategy apply known for rare or neglected...
The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such sleeping sickness, Chagas' disease, and malaria. homology the human cathepsins suggests that inhibitors originally developed for latter may be source promising lead compounds former. We describe here screening unique ∼ 2,100-member cathepsin inhibitor library against five thought relevant in diseases. Compounds active enzymes were subsequently...
ABSTRACT Entamoeba histolytica and Giardia lamblia are anaerobic protozoan parasites that cause amebiasis giardiasis, two of the most common diarrheal diseases worldwide. Current therapy relies on metronidazole, but resistance has been reported drug significant adverse effects. Therefore, it is critical to search for effective, better-tolerated antiamebic antigiardial drugs. We synthesized several examples a recently class Hsp90 inhibitors evaluated these compounds as potential leads...
Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia Entamoeba histolytica. These wreak havoc on epithelium lining small intestines (G. lamblia) colon (E. histolytica) causing giardiasis amebiasis, respectively. In addition, there less but far more deadly pathogens such as Naegleria fowleri that thrive warm waters...
Primary amebic meningoencephalitis (PAM) is a fatal infection caused by the free-living ameba Naegleria fowleri, popularly known as "brain-eating ameba". The drugs of choice in treating PAM are antifungal amphotericin B and an antileishmanial miltefosine, but these not FDA-approved for this indication use associated with severe adverse effects. Moreover, very few patients treated combination therapy have survived PAM. Therefore, development efficient critical unmet need to avert future...
Naegleria fowleri is a free-living amoeba that can also act as an opportunistic pathogen causing severe brain infection, primary amebic meningoencephalitis (PAM), in humans. The high mortality rate of PAM (exceeding 97%) attributed to (i) delayed diagnosis, (ii) lack safe and effective anti-N. drugs, (iii) difficulty delivering drugs the brain. Our work addresses identification new molecular targets may link anti-Naegleria drug discovery existing pharmacopeia brain-penetrant drugs. Using...
Current treatments for Acanthamoeba keratitis rely on a combination of chlorhexidine gluconate, propamidine isethionate, and polyhexamethylene biguanide. These disinfectants are nonspecific inherently toxic, which limits their effectiveness. Furthermore, in 10% cases, recurrent infection ensues due to the difficulty killing both trophozoites double-walled cysts. Therefore, development efficient, safe, target-specific drugs capable preventing is critical unmet need averting blindness. Since...
Primary amebic meningoencephalitis, caused by brain infection with a free-living ameba, Naegleria fowleri, leads to extensive inflammation of the and death within 3–7 days after symptoms begin. Treatment primary meningoencephalitis relies on amphotericin B in combination other drugs, but use is associated severe adverse effects. Despite fatality rate over 97%, economic incentive invest development antiamebic drugs pharmaceutical industry lacking. Development safe rapidly acting remains...
Parasitic infections are a major source of human suffering, mortality, and economic loss, but drug development for these diseases has been stymied by the significant expense involved in bringing though clinical trials to market. Identification single compounds active against multiple parasitic pathogens could improve incentives as well simplifying treatment regimens. We recently performed screen repurposed protozoan parasite Entamoeba histolytica, causative agent amebic dysentery, identified...
Introduction: Naegleria fowleri is responsible for primary amebic meningoencephalitis (PAM) which has a fatality rate of >97%. Because the rarity disease, pharmaceutical companies do not pursue new drug discovery PAM. Yet, it possible that infection underreported and finding better would have an impact on people suffering from this deadly infection.Areas covered: This paper reports efforts undertaken by different academic groups over last 20 years to test compounds against N. fowleri. The...