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Erythema nodosum-like lesions in a renal transplant recipient

Yap FB, Lee BR

Arch Dermatol, 2011 Jun;147(6):735-40.
PMID: 21690541 DOI: 10.1001/archdermatol.2011.128-a
Matched MeSH terms: Amebiasis/drug therapy
Fulltext Cobalt nanoparticles as novel nanotherapeutics against Acanthamoeba castellanii

Anwar A, Numan A, Siddiqui R, Khalid M, Khan NA

Parasit Vectors, 2019 Jun 03;12(1):280.
PMID: 31159839 DOI: 10.1186/s13071-019-3528-2

BACKGROUND: Species of Acanthamoeba are facultative pathogens which can cause sight threatening Acanthamoeba keratitis and a rare but deadly brain infection, granulomatous amoebic encephalitis. Due to conversion of Acanthamoeba trophozoites to resistant cyst stage, most drugs are found to be ineffective at preventing recurrence of infection. This study was designed to test the antiacanthamoebic effects of different cobalt nanoparticles (CoNPs) against trophozoites and cysts, as well as parasite-mediated host cell cytotoxicity.
METHODS: Three different varieties of CoNPs were synthesized by utilizing hydrothermal and ultrasonication methods and were thoroughly characterized by X-ray diffraction and field emission scanning electron microscopy. Amoebicidal, encystation, excystation, and host cell cytopathogenicity assays were conducted to study the antiacanthamoebic effects of CoNPs.
RESULTS: The results of the antimicrobial evaluation revealed that cobalt phosphate Co3(PO4)2 hexagonal microflakes, and 100 nm large cobalt hydroxide (Co(OH)2) nanoflakes showed potent amoebicidal activity at 100 and 10 µg/ml against Acanthamoeba castellanii as compared to granular cobalt oxide (Co3O4) of size 35-40 nm. Furthermore, encystation and excystation assays also showed consistent inhibition at 100 µg/ml. CoNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release without causing significant damage to human cells when treated alone.
CONCLUSIONS: To our knowledge, these findings determined, for the first time, the effects of composition, size and morphology of CoNPs against A. castellanii. Co3(PO4)2 hexagonal microflakes showed the most promising antiamoebic effects as compared to Co(OH)2 nanoflakes and granular Co3O4. The results reported in the present study hold potential for the development of antiamoebic nanomedicine.

Matched MeSH terms: Amebiasis/drug therapy
The treatment of amoebiasis with metronidazole in Malaysia

O'Holohan DR, Hugoe-Mathews J

Ann Trop Med Parasitol, 1970 Dec;64(4):475-9.
PMID: 5276552
Matched MeSH terms: Amebiasis/drug therapy*
Brain-eating Amoebae Infection: Challenges and Opportunities in Chemotherapy

Mungroo MR, Anwar A, Khan NA, Siddiqui R

Mini Rev Med Chem, 2019;19(12):980-987.
PMID: 30868950 DOI: 10.2174/1389557519666190313161854

Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as "brain-eating amoebae". The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections.

Matched MeSH terms: Amebiasis/drug therapy*
Fulltext PLGA nanoparticles loaded with Gallic acid- a constituent of Leea indica against Acanthamoeba triangularis

Mahboob T, Nawaz M, de Lourdes Pereira M, Tian-Chye T, Samudi C, Sekaran SD, et al.

Sci Rep, 2020 06 02;10(1):8954.
PMID: 32488154 DOI: 10.1038/s41598-020-65728-0

Acanthamoeba, a genus that contains at least 24 species of free-living protozoa, is ubiquitous in nature. Successful treatment of Acanthamoeba infections is always very difficult and not always effective. More effective drugs must be developed, and medicinal plants may have a pivotal part in the future of drug discovery. Our research focused on investigating the in vitro anti- acanthamoebic potential of Leea indica and its constituent gallic acid in different concentrations. Water and butanol fractions exhibited significant amoebicidal activity against trophozoites and cysts. Gallic acid (100 µg/mL) revealed 83% inhibition of trophozoites and 69% inhibition of cysts. The butanol fraction induced apoptosis in trophozoites, which was observed using tunnel assay. The cytotoxicity of the fractions and gallic acid was investigated against MRC-5 and no adverse effects were observed. Gallic acid was successfully loaded within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with 82.86% encapsulation efficiency, while gallic acid showed 98.24% in vitro release at 48 hours. Moreover, the gallic acid encapsulated in the PLGA nanoparticles exhibited 90% inhibition against trophozoites. In addition, gallic acid encapsulated nanoparticles showed reduced cytotoxicity towards MRC-5 compared to gallic acid, which evidenced that natural product nanoencapsulation in polymeric nanoparticles could play an important role in the delivery of natural products.

Matched MeSH terms: Amebiasis/drug therapy*
Fulltext Gold Nanoparticle-Conjugated Cinnamic Acid Exhibits Antiacanthamoebic and Antibacterial Properties

Anwar A, Siddiqui R, Shah MR, Khan NA

Antimicrob Agents Chemother, 2018 09;62(9).
PMID: 29967024 DOI: 10.1128/AAC.00630-18

trans-Cinnamic acid (CA) is a natural organic compound. Using amoebicidal assays, for the first time we showed that CA affected the viability of the protist pathogen Acanthamoeba castellanii Conjugation with gold nanoparticles (AuNPs) enhanced the antiamoebic effects of CA. CA-coated AuNPs (CA-AuNPs) also exhibited significant excystation and encystation activity, compared to CA and AuNPs alone. Pretreatment of amoebae with CA-AuNPs inhibited A. castellanii-mediated host cell cytotoxicity. Moreover, CA-AuNPs exhibited potent effects against methicillin-resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1 and protected host cells against bacteria-mediated host cell death.

Matched MeSH terms: Amebiasis/drug therapy
Single-dose and short course regimens of metronidazole in the treatment of amoebiasis in Malaysia

O'Holohan DR, Hugoe-Matthews J

Ann Trop Med Parasitol, 1972 Jun;66(2):181-6.
PMID: 4338870
Matched MeSH terms: Amebiasis/drug therapy*
Antiamoebic activity of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one library against Acanthamoeba castellanii

Shahbaz MS, Anwar A, Saad SM, Kanwal, Anwar A, Khan KM, et al.

Parasitol Res, 2020 Jul;119(7):2327-2335.
PMID: 32476058 DOI: 10.1007/s00436-020-06710-7

Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.

Matched MeSH terms: Amebiasis/drug therapy
Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole

Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA

Parasitol Res, 2018 Jan;117(1):265-271.
PMID: 29218442 DOI: 10.1007/s00436-017-5701-x

Infectious diseases are the leading cause of morbidity and mortality, killing more than 15 million people worldwide. This is despite our advances in antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising technology to enhance drug efficacy and formation of effective vehicles for drug delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes), and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were synthesized successfully and characterized by ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba castellanii belonging to the T4 genotype using amoebicidal assay and host cell cytotoxicity assay. Viability assays revealed that silver nanoparticles conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited significant antiamoebic properties compared with drugs alone or AgNPs alone (P drugs inhibited amoebae-mediated host cell cytotoxicity as determined by measuring lactate dehydrogenase release. Overall, here we present the development of a new formulation of more effective antiamoebic agents based on AgNPs coated with drugs that hold promise for future applications.

Matched MeSH terms: Amebiasis/drug therapy*
Fulltext Antimicrobial activities of green synthesized gums-stabilized nanoparticles loaded with flavonoids

Anwar A, Masri A, Rao K, Rajendran K, Khan NA, Shah MR, et al.

Sci Rep, 2019 02 28;9(1):3122.
PMID: 30816269 DOI: 10.1038/s41598-019-39528-0

Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100-225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.

Matched MeSH terms: Amebiasis/drug therapy