Displaying publications 41 - 60 of 100 in total

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  1. Fulltext Antiamoebic activity of plant-based natural products and their conjugated silver nanoparticles against Acanthamoeba castellanii (ATCC 50492)
    Anwar A, Ting ELS, Anwar A, Ain NU, Faizi S, Shah MR, et al.
    AMB Express, 2020 Feb 03;10(1):24.
    PMID: 32016777 DOI: 10.1186/s13568-020-0960-9
    Acanthamoeba spp. are the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis (GAE). The current options to treat Acanthamoeba infections have limited success. Silver nanoparticles show antimicrobial effects and enhance the efficacy of their payload at the specific biological targets. Natural folk plants have been widely used for treating diseases as the phytochemicals from several plants have been shown to exhibit amoebicidal effects. Herein, we used natural products of plant or commercial sources including quercetin (QT), kolavenic acid (PGEA) isolated from plant extracts of Polyalthia longifolia var pendula and crude plant methanolic extract of Caesalpinia pulcherrima (CPFLM) as antiacanthamoebic agents. Furthermore, these plant-based materials were conjugated with silver nanoparticles (AgNPs) to determine the effects of the natural compounds and their nanoconjugates against a clinical isolate of A. castellanii from a keratitis patient (ATCC 50492) belonging to the T4 genotype. The compounds were conjugated with AgNPs and characterized by using ultraviolet visible spectrophotometry and atomic force microscopy. Quercetin coated silver nanoparticles (QT-AgNPs) showed characteristic surface plasmon resonance band at 443 nm and the average size distribution was found to be around 45 nm. The natural compounds alone and their nanoconjugates were tested for the viability of amoebae, encystation and excystation activity against A. castellanii. The natural compounds showed significant growth inhibition of A. castellanii while QT-AgNPs specifically exhibited enhanced antiamoebic effects as well as interrupted the encystation and excystation activity of the amoebae. Interestingly, these compounds and nanoconjugates did not exhibit in vitro cytotoxic effects against human cells. Plant-based compounds and extracts could be an interesting strategy in development of alternative therapeutics against Acanthamoeba infections.
  2. Fulltext Metronidazole conjugated magnetic nanoparticles loaded with amphotericin B exhibited potent effects against pathogenic Acanthamoeba castellanii belonging to the T4 genotype
    Abdelnasir S, Anwar A, Kawish M, Anwar A, Shah MR, Siddiqui R, et al.
    AMB Express, 2020 Jul 17;10(1):127.
    PMID: 32681358 DOI: 10.1186/s13568-020-01061-z
    Acanthamoeba castellanii can cause granulomatous amoebic encephalitis and Acanthamoeba keratitis. Currently, no single drug has been developed to effectively treat infections caused by Acanthamoeba. Recent studies have shown that drugs conjugated with nanoparticles exhibit potent in vitro antiamoebic activity against pathogenic free-living amoebae. In this study, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with metronidazole which were further loaded with amphotericin B to produce enhanced antiamoebic effects against Acanthamoeba castellanii. The results showed that metronidazole-nanoparticles-amphotericin B (Met-MNPs-Amp) significantly inhibited the viability of these amoebae as compared to the respective controls including drugs and nanoparticles alone. Met-MNPs-Amp exhibited IC50 at 50 μg/mL against both A. castellanii trophozoites and cysts. Furthermore, these nanoparticles did not affect the viability of rat and human cells and showed safe hemolytic activity. Hence, the results obtained in this study have potential utility in drug development against infections caused by Acanthamoeba castellanii. A combination of drugs can lead to successful prognosis against these largely neglected infections. Future studies will determine the value of conjugating molecules with diagnostic and therapeutic potential to provide theranostic approaches against these serious infections.
  3. Synthetic nanoparticle-conjugated bisindoles and hydrazinyl arylthiazole as novel antiamoebic agents against brain-eating amoebae
    Kanwal, Mungroo MR, Anwar A, Ali F, Khan S, Abdullah MA, et al.
    Exp Parasitol, 2020 Nov;218:107979.
    PMID: 32866583 DOI: 10.1016/j.exppara.2020.107979
    Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.
  4. Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba
    Walvekar S, Anwar A, Anwar A, Sridewi N, Khalid M, Yow YY, et al.
    Acta Trop, 2020 Nov;211:105618.
    PMID: 32628912 DOI: 10.1016/j.actatropica.2020.105618
    Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major end-product in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time.
  5. Antimicrobial properties of multifunctional polypyrrole-cobalt oxide-silver nanocomposite against pathogenic bacteria and parasite
    Masri A, Abdelnasir S, Anwar A, Iqbal J, Numan A, Jagadish P, et al.
    Appl Microbiol Biotechnol, 2021 Apr;105(8):3315-3325.
    PMID: 33797573 DOI: 10.1007/s00253-021-11221-1
    BACKGROUND: Conducting polymer based nanocomposites are known to be effective against pathogens. Herein, we report the antimicrobial properties of multifunctional polypyrrole-cobalt oxide-silver nanocomposite (PPy-Co3O4-AgNPs) for the first time. Antibacterial activities were tested against multi-drug-resistant Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteria, while antiamoebic effects were assessed against opportunistic protist Acanthamoeba castellanii (A. castellanii).

    RESULTS: The ternary nanocomposite containing conducting polymer polypyrrole, cobalt oxide, and silver nanoparticles showed potent antimicrobial effects against these pathogens. The antibacterial assay showed that PPy-Co3O4-AgNPs exhibited significant bactericidal activity against neuropathogenic E. coli K1 at only 8 μg/mL as compared to individual components of the nanocomposite, whereas a 70 % inhibition of A. castellanii viability was observed at 50 μg/mL. Moreover, PPy-Co3O4-AgNPs were found to have minimal cytotoxicity against human keratinocytes HaCaT cells in vitro even at higher concentration (50 μg/mL), and also reduced the microbes-mediated cytopathogenicity against host cells.

    CONCLUSION: These results demonstrate that PPy-Co3O4-AgNPs hold promise in the development of novel antimicrobial nanomaterials for biomedical applications.

    KEY POINTS: •Synthesis of polypyrrole-cobalt oxide-silver (PPy-Co3O4-AgNPs) nanocomposite. •Antimicrobial activity of nanocomposite. •PPy-Co3O4-AgNPs hold promise for biomedical applications.

  6. Performance of Body Mass Index in Identifying Obesity Defined by Body Fat Percentage and Hypertension Among Malaysian Population: A Retrospective Study
    Aizuddin AN, Chan CM, Anwar AR, Ong YX, Chin KY
    Int J Gen Med, 2021;14:3251-3257.
    PMID: 34267543 DOI: 10.2147/IJGM.S316360
    Purpose: Body mass index (BMI) is used universally to define obesity. Many studies have indicated that the current BMI cutoff value for obesity may be inaccurate in identifying individuals with excess body fat (BF) and at risk for cardiovascular diseases (CVD). This study aims to assess the performance of BMI in diagnosing obesity defined by BF percentage (BF%).

    Patients and Methods: A total of 136 participants who attended an annual health screening programme were recruited. The subjects completed the health examinations, including BMI, BF% and blood pressure measurement. A receiver operating curve (ROC) analysis was conducted to determine the optimal cutoff value of BMI in classifying obesity based on BF% (>25%).

    Results: The ROC analysis revealed that the optimal BMI cutoff value in classifying subjects with obesity based on BF% was 24.8 kg/m2. The agreement between the classification scheme based on the new BMI cutoff (>24.8 kg/m2) and BF% was higher (κ=0.722) compared to the standard BMI cutoff (>27.5 kg/m2) (κ=0.532). BMI 24.8 kg/m2 also had higher sensitivity (80.0%) than 27.5 kg/m2 (56.0%) in detecting subjects with high adiposity. The new BMI cutoff also showed a sensitivity of 63.9% in identifying subjects with hypertension compared to the standard cutoff (36.1%).

    Conclusion: The current definition of obesity based on BMI value needs to be reassessed by taking BF% into account. A new BMI cutoff point, 24.8 kg/m2 for obesity, can identify a higher percentage of Malaysian at risk for CVD.

  7. Fulltext A Comparative Study of Cytotoxicity of PPG and PEG Surface-Modified 2-D Ti3C2 MXene Flakes on Human Cancer Cells and Their Photothermal Response
    Rashid B, Anwar A, Shahabuddin S, Mohan G, Saidur R, Aslfattahi N, et al.
    Materials (Basel), 2021 Aug 04;14(16).
    PMID: 34442891 DOI: 10.3390/ma14164370
    The MXenes are a novel family of 2-D materials with promising biomedical activity, however, their anticancer potential is still largely unexplored. In this study, a comparative cytotoxicity investigation of Ti3C2 MXenes with polypropylene glycol (PPG), and polyethylene glycol (PEG) surface-modified 2-D Ti3C2 MXene flakes has been conducted towards normal and cancerous human cell lines. The wet chemical etching method was used to synthesize MXene followed by a simple chemical mixing method for surface modification of Ti3C2 MXene with PPG and PEG molecules. SEM and XRD analyses were performed to examine surface morphology and elemental composition, respectively. FTIR and UV-vis spectroscopy were used to confirm surface modification and light absorption, respectively. The cell lines used to study the cytotoxicity of MXene and surface-modified MXenes in this study were normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells. These cell lines were also used as controls (without exposure to study material and irradiation) to measure their baseline cell viability under the same lab environment. The surface-modified MXenes exhibited a sharp reduction in cell viability towards both normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells but cytotoxicity was more pronounced towards cancerous cell lines. This may be due to the difference in cell metabolism and the occurrence of high pre-existing levels of reactive oxygen species (ROS) within cancerous cells. The highest toxicity towards both normal and cancerous cell lines was observed with PEGylated MXenes followed by PPGylated and bare MXenes. The normal cell's viability was barely above 70% threshold with 250 mg/L PEGylated MXene concentration whereas PPGylated and bare MXene were less toxic towards normal cells, even at 500 mg/L concentration. Moreover, the toxicity was found to be directly related to the type of cell lines. In general, the HaCaT cell line exhibited the lowest toxicity while toxicity was highest in the case of the A375 cell line. The photothermal studies revealed high photo response for PEGylated MXene followed by PPGylated and bare MXenes. However, the PPGylated MXene's lower cytotoxicity towards normal cells while comparable toxicity towards malignant cells as compared to PEGylated MXenes makes the former a relatively safe and effective anticancer agent.
  8. Polyaniline-Conjugated Boron Nitride Nanoparticles Exhibiting Potent Effects against Pathogenic Brain-Eating Amoebae
    Abdelnasir S, Mungroo MR, Shahabuddin S, Siddiqui R, Khan NA, Anwar A
    ACS Chem Neurosci, 2021 Oct 06;12(19):3579-3587.
    PMID: 34545742 DOI: 10.1021/acschemneuro.1c00179
    Free-living amoebae include Acanthamoeba castellanii and Naegleria fowleri that are opportunistic protozoa responsible for life-threatening central nervous system infections with mortality rates over 90%. The rising number of cases and high mortality rates are indicative of the critical unmet need for the development of efficient drugs in order to avert future deaths. In this study, we assess the anti-amoebic capacity of a conducting polymer nanocomposite comprising polyaniline (PANI) and hexagonal boron nitride (hBN) against A. castellanii and N. fowleri. We observed significant amoebicidal and cysticidal effects using 100 μg/mL PANI/hBN (P < 0.05). Further, the nanocomposite demonstrated negligible cytotoxicity toward HaCaT and primary human corneal epithelial cells (pHCECs). In evaluating the mode of inhibition of A. castellanii due to treatment with PANI/hBN, increased intracellular reactive oxygen species (ROS) was measured and scanning microscopy visualized the formation of pores in the amoebae. Overall, this study is suggestive of the potential of the PANI/hBN nanocomposite as a promising therapy for amoeba infections.
  9. Pyrazinium thioacetate capped gold nanoparticles as Fe(III) sensor and Fe(III) marked anti-proliferating agent in human neuroblastoma cells
    Anwar A, Minhaz A, Hussain SS, Anwar A, Simjee SU, Ishaq M, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2019 Jan 05;206:135-140.
    PMID: 30096697 DOI: 10.1016/j.saa.2018.07.099
    Gold nanoparticles (AuNPs) stabilized by new cationic 1‑(3‑(acetylthio)propyl)pyrazin‑1‑ium ligand (PPTA) were synthesized. AuNPs stabilized by PPTA (PPTA-AuNPs) were found to be spherical and polydispersed with the average size of 60 nm. Human neuroblastoma (SHSY-5Y) cells permeability of PPTA-AuNPs was found to be a key feature to study the intracellular quenching of Fe(III) proliferative activity. In vitro MTT assay revealed non-cytotoxicity of PPTA and PPTA-AuNPs at 100 μM concentration, while treatment of 100 μM of Fe(III) with SHSY-5Y cells resulted into higher cells viability. Contrary, a mixture of 1:1 Fe(III) with PPTA-AuNPs showed no change in the viability of cells at same concentration which suggests the intracellular complexation and recognition of Fe(III) by PPTA-AuNPs. AFM morphological analysis of SHSY-5Y cells also supported the MTT assay results, and it is safe to conclude that PPTA-AuNPs can be used as Fe(III) probes in living cells. In addition, Fe(III) caused a significant decrease in the absorbance of surface plasmon resonance (SPR) band of PPTA-AuNPs in a wide range of concentration and pH, with limit of detection 4.3 μM. Moreover, the specific response of PPTA-AuNPs towards Fe(III) was unaffected by the interference of other metals and components of real samples of tap water.
  10. Effects of Shape and Size of Cobalt Phosphate Nanoparticles against Acanthamoeba castellanii
    Anwar A, Chi Fung L, Anwar A, Jagadish P, Numan A, Khalid M, et al.
    Pathogens, 2019 Nov 22;8(4).
    PMID: 31766722 DOI: 10.3390/pathogens8040260
    T4 genotype Acanthamoeba are opportunistic pathogens that cause two types of infections, including vision-threatening Acanthamoeba keratitis (AK) and a fatal brain infection known as granulomatous amoebic encephalitis (GAE). Due to the existence of ineffective treatments against Acanthamoeba, it has become a potential threat to all contact lens users and immunocompromised patients. Metal nanoparticles have been proven to have various antimicrobial properties against bacteria, fungi, and parasites. Previously, different types of cobalt nanoparticles showed some promise as anti-acanthamoebic agents. In this study, the objectives were to synthesize and characterize the size, morphology, and crystalline structure of cobalt phosphate nanoparticles, as well as to determine the effects of different sizes of cobalt metal-based nanoparticles against A. castellanii. Cobalt phosphate octahydrate (CHP), Co3(PO4)2•8H2O, was synthesized by ultrasonication using a horn sonicator, then three different sizes of cobalt phosphates Co3(PO4)2 were produced through calcination of Co3(PO4)2•8H2O at 200 °C, 400 °C and 600 °C (CP2, CP4, CP6). These three types of cobalt phosphate nanoparticles were characterized using a field emission scanning electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analysis. Next, the synthesized nanoparticles were subjected to biological assays to investigate their amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects against A. castellanii, as well as cell cytotoxicity. The overall results showed that 1.30 ± 0.70 µm of CHP microflakes demonstrated the best anti-acanthemoebic effects at 100 µg/mL, followed by 612.50 ± 165.94 nm large CP6 nanograins. However, amongst the three tested cobalt phosphates, Co3(PO4)2, the smaller nanoparticles had stronger antiamoebic effects against A. castellanii. During cell cytotoxicity analysis, CHP exhibited only 15% cytotoxicity against HeLa cells, whereas CP6 caused 46% (the highest) cell cytotoxicity at the highest concentration, respectively. Moreover, the composition and morphology of nanoparticles is suggested to be important in determining their anti-acathamoebic effects. However, the molecular mechanisms of cobalt phosphate nanoparticles are still unidentified. Nevertheless, the results suggested that cobalt phosphate nanoparticles hold potential for development of nanodrugs against Acanthamoeba.
  11. Oleic acid-conjugated silver nanoparticles as efficient antiamoebic agent against Acanthamoeba castellanii
    Anwar A, Abdalla SAO, Aslam Z, Shah MR, Siddiqui R, Khan NA
    Parasitol Res, 2019 Jul;118(7):2295-2304.
    PMID: 31093751 DOI: 10.1007/s00436-019-06329-3
    Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 μM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 μM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.
  12. Aryl Quinazolinone Derivatives as Novel Therapeutic Agents against Brain-Eating Amoebae
    Mungroo MR, Shahbaz MS, Anwar A, Saad SM, Khan KM, Khan NA, et al.
    ACS Chem Neurosci, 2020 08 19;11(16):2438-2449.
    PMID: 31961126 DOI: 10.1021/acschemneuro.9b00596
    Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris. Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro. The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly (P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
  13. Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles
    Hussain MA, Ahmed D, Anwar A, Perveen S, Ahmed S, Anis I, et al.
    Int Microbiol, 2019 Jun;22(2):239-246.
    PMID: 30810990 DOI: 10.1007/s10123-018-00043-3
    Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.
  14. Fulltext Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae
    Anwar A, Mungroo MR, Khan S, Fatima I, Rafique R, Kanwal, et al.
    Antibiotics (Basel), 2020 Apr 17;9(4).
    PMID: 32316387 DOI: 10.3390/antibiotics9040188
    Balamuthia mandrillaris and Naegleriafowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
  15. Fulltext Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii
    Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.
    Antibiotics (Basel), 2020 May 25;9(5).
    PMID: 32466210 DOI: 10.3390/antibiotics9050276
    The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.
  16. 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.
  17. Antiamoebic activity of synthetic tetrazoles against Acanthamoeba castellanii belonging to T4 genotype and effects of conjugation with silver nanoparticles
    Anwar A, Yi YP, Fatima I, Khan KM, Siddiqui R, Khan NA, et al.
    Parasitol Res, 2020 Jun;119(6):1943-1954.
    PMID: 32385711 DOI: 10.1007/s00436-020-06694-4
    Acanthamoeba causes diseases such as Acanthamoeba keratitis (AK) which leads to permanent blindness and granulomatous Acanthamoeba encephalitis (GAE) where there is formation of granulomas in the brain. Current treatments such as chlorhexidine, diamidines, and azoles either exhibit undesirable side effects or require immediate and prolonged treatment for the drug to be effective or prevent relapse. Previously, antifungal drugs amphotericin B, nystatin, and fluconazole-conjugated silver with nanoparticles have shown significantly increased activity against Acanthamoeba castellanii. In this study, two functionally diverse tetrazoles were synthesized, namely 5-(3-4-dimethoxyphenyl)-1H-tetrazole and 1-(3-methoxyphenyl)-5-phenoxy-1H-tetrazole, denoted by T1 and T2 respectively. These compounds were evaluated for anti-Acanthamoeba effects at different concentrations ranging from 5 to 50 μM. Furthermore, these compounds were conjugated with silver nanoparticles (AgNPs) to enhance their efficacy. Particle size analysis showed that T1-AgNPs and T2-AgNPs had an average size of 52 and 70 nm respectively. After the successful synthesis and characterization of tetrazoles and tetrazole-conjugated AgNPs, they were subjected to anti-Acanthamoeba studies. Amoebicidal assay showed that at concentration 10 μM and above, T2 showed promising antiamoebic activities between the two compounds while encystation and excystation assays reveal that both T1 and T2 have inhibited differentiation activity against Acanthamoeba castellanii. Conjugation of T1 and T2 to AgNP also increased efficacy of tetrazoles as anti-Acanthamoeba agents. This may be due to the increased bioavailability as AgNP allows better delivery of treatment compounds to A. castellanii. Human cell cytotoxicity assay revealed that tetrazoles and AgNPs are significantly less toxic towards human cells compared with chlorhexidine which is known to cause undesirable side effects. Cytopathogenicity assay also revealed that T2 conjugated with AgNPs significantly reduced cytopathogenicity of A. castellanii compared with T2 alone, suggesting that T2-conjugated AgNP is an effective and safe anti-Acanthamoeba agent. The use of a synthetic azole compound conjugated with AgNPs can be an alternative strategy for drug development against A. castellanii. However, mechanistic and in vivo studies are needed to explore further translational values.
  18. Retraction Note to: Antiamoebic activity of synthetic tetrazoles against Acanthamoeba castellanii belonging to T4 genotype and effects of conjugation with silver nanoparticles
    Anwar A, Yi YP, Fatima I, Khan KM, Siddiqui R, Khan NA, et al.
    Parasitol Res, 2022 Mar;121(3):1073.
    PMID: 35072801 DOI: 10.1007/s00436-022-07440-8
  19. Potent antibacterial activity of MXene-functionalized graphene nanocomposites
    Salmi MS, Ahmed U, Aslfattahi N, Rahman S, Hardy JG, Anwar A
    RSC Adv, 2022 Nov 15;12(51):33142-33155.
    PMID: 36425203 DOI: 10.1039/d2ra04944a
    Two dimensional (2D) nanomaterials display properties with significant biological utility (e.g., antimicrobial activity). In this study, MXene-functionalized graphene (FG) nanocomposites with Ti3C2T x in varying ratios (FG : Ti3C2T x , 25 : 75%, 50 : 50%, and 75 : 25%) were prepared and characterized via scanning electron microscopy, scanning electron microscopy-energy dispersive X-ray (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), and zeta potential analysis. Their cytotoxicity was assessed using immortalized human keratinocytes (HaCaT) cells at three different timepoints, and antibacterial activity was assessed using Gram-positive Methicillin resistant Staphylococcus aureus, MRSA, and Gram-negative neuro-pathogenic Escherichia coli K1 (E. coli K1) in vitro. The nanomaterials and composites displayed potent antibacterial effects against both types of bacteria and low cytotoxicity against HaCaT cells at 200 μg mL-1, which is promising for their utilization for biomedical applications.
  20. CONJUGATION WITH SILVER NANOPARTICLES ENHANCES ANTI-ACANTHAMOEBIC ACTIVITY OF KAPPAPHYCUS ALVAREZII
    Walvekar S, Anwar A, Anwar A, Lai NJY, Yow YY, Khalid M, et al.
    J Parasitol, 2021 07 01;107(4):537-546.
    PMID: 34265050 DOI: 10.1645/21-41
    Nanomedicine has the potential in enhancing the efficacy and bioavailability of anti-infective agents. Here we determined whether conjugation of the Malaysian cultivated seaweed Kappaphycus alvarezii with silver-conjugated nanoparticles enhanced anti-acanthamoebic properties. Silver-conjugated K. alvarezii were successfully synthesized, followed by characterization with Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, and transmission electron microscopy. Amoebicidal effects were evaluated against Acanthamoeba castellanii, and cytotoxicity assays were performed using HaCaT cells. Viability assays revealed that silver nanoparticles conjugated with K. alvarezii extract exhibited significant antiamoebic properties (P < 0.05). Nano-conjugates induced the production of reactive oxygen species. Importantly, silver-conjugated extract inhibited amoeba-mediated host cell damage as established by lactate dehydrogenase release. Neither the nano-conjugates nor the extract showed cytotoxicity against human cells in vitro. Liquid chromatography and mass spectroscopy revealed several molecules, including 2,6-nonadien-1-ol, N-desmethyl trifluoperazine, dulciol B, lucidumol A, acetoxolone, 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol, C16 sphinganine, 22-tricosenoic acid, and β-dihydrorotenone, of which dulciol B and C16 sphinganine are known to possess antimicrobial activities. In summary, marine organisms are an important source of bioactive molecules with anti-acanthamoebic properties that can be enhanced by conjugating with silver nanoparticles. Natural products combined with nanotechnology using multifunctional nanoparticle complexes can deliver therapeutic agents effectively and hold promise in the development of new formulations of anti-acanthamoebic agents.
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