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trans-Cinnamic Acid Conjugated Gold Nanoparticles as Potent Therapeutics against Brain-Eating Amoeba Naegleria fowleri

Rajendran K, Anwar A, Khan NA, Shah MR, Siddiqui R

ACS Chem Neurosci, 2019 06 19;10(6):2692-2696.
PMID: 30970208 DOI: 10.1021/acschemneuro.9b00111

Primary amoebic meningoencephalitis (PAM), a deadly brain infection, is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin, and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95%. Moreover, severe adverse side effects are associated with these drugs. Nanotechnology has provided several advances in biomedical applications especially in drug delivery and diagnosis. Herein, for the first time we report antiamoebic properties of cinnamic acid (CA) and gold nanoparticles conjugated with CA (CA-AuNPs) against N. fowleri. CA-AuNPs were successfully synthesized by sodium borohydride reduction of tetrachloroauric acid. Size and morphology were determined by atomic force microscopy (AFM) while the surface plasmon resonance band was analyzed by ultraviolet-visible (UV-vis) spectrophotometry for the characterization of the nanoparticles. Amoebicidal and cytopathogenicity (host cell cytotoxicity) assays revealed that both CA and CA-AuNPs displayed significant anti- N. fowleri properties ( P < 0.05), whereas nanoparticles conjugation further enhanced the anti- N. fowleri effects of CA. This study established a potential drug lead, while CA-AuNPs appear to be promising candidate for drug discovery against PAM.
Validity and Reliability of the Golombok Rust Inventory of Sexual Satisfaction in Couples with Incontinent Partners

Lim R, Liong ML, Khan NA, Yuen KH

J Sex Marital Ther, 2017 Feb 17;43(2):142-146.
PMID: 26836418 DOI: 10.1080/0092623X.2016.1141817

There is currently no published information on the validity and reliability of the Golombok Rust Inventory of Sexual Satisfaction in the Asian population, specifically in patients with stress urinary incontinence, which limits its use in this region. Our study aimed to evaluate the psychometric properties of this questionnaire in the Malaysian population. Ten couples were recruited for the pilot testing. The agreement between the English and Chinese or Malay versions were tested using the intraclass correlation coefficients, with results of more than 0.80 for all subscales and overall scores indicating good agreement. Sixty-six couples were included in the subsequent phase. The following data are presented in the order of English, Chinese, and Malay. Cronbach's alphas for the male total score were 0.82, 0.88, and 0.95. For the female total score, Cronbach's alphas were 0.76, 0.78, and 0.88. Intraclass correlation coefficients for the male total score were 0.93, 0.94, and 0.99, while intraclass correlation coefficients for the female total score were 0.89, 0.86, and 0.88. In conclusion, the English, Chinese, and Malay versions each proved to be valid and reliable in our Malaysian population.
Unraveling the Differentially Articulated Axes of the Century-Old Renin-Angiotensin-Aldosterone System: Potential Therapeutic Implications

Balakumar P, Handa S, Alqahtani A, Alqahtani T, Khan NA, LakshmiRaj RS, et al.

Cardiovasc Toxicol, 2022 Feb 10.
PMID: 35143015 DOI: 10.1007/s12012-022-09724-y

Among numerous choices in cardiovascular therapies used for the management of hypertension and heart failure, drugs affecting the renin-angiotensin-aldosterone system (RAAS) hold substantial therapeutic roles. Therapies aimed at modifying the RAAS and its overactivation are employed for the management of various insidious disorders. In the pharmacologic perspective, RAAS is one of the frequently manipulated systems for the management of hypertension, heart failure, myocardial infarction, and renal disease. The RAAS pharmacologic interventions principally include the ACE inhibitors, the angiotensin II-AT1 receptor blockers, the mineralocorticoid receptor antagonists, and the direct renin inhibitors. In addition, therapeutic implication of ACE2/angiotensin (1-7)/Mas receptor activation using various ligands is being explored owing to their anti-inflammatory, anti-fibrotic, vasodilatory, and cardiovascular defensive roles. Moreover, being considered as the counter-regulatory arm of AT1 receptor, the potential role of AT2 receptor activation using selective AT2 receptor agonist is currently investigated for its efficacy in pulmonary complications. As an important regulator of fluid volume, blood pressure, and cardiovascular-renal function, the RAAS has been documented as a diversified intricate system with several therapeutic possibilities coupled with their fundamental structural and functional modulatory roles in cardiovascular, renal, and other systems. The RAAS possesses a number of regulatory, deregulatory, and counter-regulatory axes of physiopathologic importance in health and disease. The counter-regulatory arms of the RAAS might play an essential role in mitigating cardiovascular, renal, and pulmonary pathologies. In light of this background, we sought to explore the classical and counter-regulatory axes/arms of the RAAS and their imperative roles in physiologic functions and disease pathogenesis.
Fulltext Understanding the impacts of the COVID-19 pandemic on sustainable agri-food system and agroecosystem decarbonization nexus: A review

Adelodun B, Kareem KY, Kumar P, Kumar V, Choi KS, Yadav KK, et al.

J Clean Prod, 2021 Oct 10;318:128451.
PMID: 36570877 DOI: 10.1016/j.jclepro.2021.128451

The existing finite natural resources have witnessed unsustainable usage in the past few years, especially for food production, with accompanying environmental devastation and ecosystem damage. Regrettably, the global population and consumption demands are increasing ceaselessly, leading to the need for more resources for food production, which could potentially aggravate the sustainability and ecosystem degradation issues, while stimulating drastic climate change. Meanwhile, the unexpected emergence of the COVID-19 pandemic and some implemented measures to combat its spread disrupted agricultural activities and the food supply chain, which also led to a reduction in ecosystem carbonization. This study sets out to explore policy framework and selected feasible actions that are being adopted during the COVID-19 pandemic, which could potentially reduce the emissions even after the pandemic to promote a resilient and sustainable agri-food system. In this study, we reviewed 27 articles that focus on the current state of the agri-food system in light of the COVID-19 pandemic and its impact on the decarbonization of the agroecosystem. This review has taken the form of a systematic methodology in analyzing the adoption and implementation of various measures to mitigate the spread of COVID-19 on the impact of the agri-food system and reduction in ecosystem degradation. Up to 0.3 Mt of CO2 reduction from the agri-food system alone was reportedly achieved during the first 6 months of the pandemic in 23 European countries. The various adopted measures indicate that the circular economy approach is a panacea to achieve the needed sustainability in the agri-food system. Also, it dictates a need for a paradigm change towards improvement on localized food production that promotes sustainable production and consumption.
Uncovering Potentially Therapeutic Phytochemicals, In silico Analysis, and Biological Assessment of South-Chinese Red Dragon Fruit (Hylocereus polyrhizus)

Asghar A, Huichun L, Fang Q, Khan NA, Shahid M, Rui W, et al.

Plant Foods Hum Nutr, 2024 Feb 16.
PMID: 38363439 DOI: 10.1007/s11130-024-01151-4

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate
Treatment of Hospital wastewater with submerged aerobic fixed film reactor coupled with tube-settler

Khan NA, Bokhari A, Mubashir M, Klemeš JJ, El Morabet R, Khan RA, et al.

Chemosphere, 2022 Jan;286(Pt 3):131838.
PMID: 34399260 DOI: 10.1016/j.chemosphere.2021.131838

In this study, Hospital wastewater was treated using a submerged aerobic fixed film (SAFF) reactor coupled with tubesettler in series. SAFF consisted of a column with an up-flow biofilter. The biological oxygen demand (BOD)5, chemical oxygen demand (COD), nitrate and phosphate were the chosen pollutants for evaluation. The pollutants removal efficiency was determined at varying organic loading rates and hydraulic retention time. The organic loading rate was varied between 0.25 and 1.25 kg COD m-3 d-1. The removal efficiency of SAFF and tubesettler combined was 75 % COD, 67 % BOD and 67 % phosphate, respectively. However, nitrate saw an increase in concentration by 25 %. SAFF contribution in the removal of COD, BOD5 and Phosphate was 48 %, 46 % and 29 %, respectively. While for accumulation of nitrate, it was responsible for 56%, respectively. Tubesettler performed better than SAFF with 52 %, 54 % and 69 % reduction of COD, BOD5 and phosphate, respectively. But in terms of nitrate, tubesettler was responsible for 44 % accumulation. The nutrient reduction decreased with an increase in the organic loading rate. Nitrification was observed in the SAFF and tubesettler, which indicated a well-aerated system. An anaerobic unit is required for completing the denitrification process and removing nitrogen from the effluent. The better performance of tubesettler over SAFF calls for necessitates extended retention time over design criteria. Further studies are beneficial to investigate the impact of pharmaceutical compounds on the efficiency of SAFF.
Fulltext Transcriptome analysis of Escherichia coli K1 after therapy with hesperidin conjugated with silver nanoparticles

Masri A, Khan NA, Zoqratt MZHM, Ayub Q, Anwar A, Rao K, et al.

BMC Microbiol, 2021 Feb 17;21(1):51.
PMID: 33596837 DOI: 10.1186/s12866-021-02097-2

BACKGROUNDS: Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study.
RESULTS: 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P
Fulltext Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial

Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, et al.

Nutr J, 2013;12(1):166.
PMID: 24373555 DOI: 10.1186/1475-2891-12-166

Nonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.
Timing of The First Zygotic Cleavage Affects Post-Vitrification Viability of Murine Embryos Produced In Vivo

Jusof WH, Khan NA, Rajikin MH, Satar NA, Mustafa MF, Jusoh N, et al.

Int J Fertil Steril, 2015 07 27;9(2):221-9.
PMID: 26246881

BACKGROUND: Timing of the first zygotic cleavage is an accurate predictor of embryo quality. Embryos that cleaved early (EC) have been shown to exhibit higher develop- mental viability compared to those that cleaved at a later period (LC). However, the vi- ability of EC embryos in comparison to LC embryos after vitrification is unknown. The present study aims to investigate the post-vitrification developmental viability of murine EC versus LC embryos.
MATERIALS AND METHODS: In this experimental study, female ICR mice (6-8 weeks old) were superovulated and cohabited with fertile males for 24 hours. Afterwards, their ovi- ducts were excised and embryos harvested. Embryos at the 2-cell stage were catego- rized as EC embryos, while zygotes with two pronuclei were categorized as LC embryos. Embryos were cultured in M16 medium supplemented with 3% bovine serum albumin (BSA) in a humidified 5% CO2atmosphere. Control embryos were cultured until the blastocyst stage without vitrification. Experimental embryos at the 2-cell stage were vitri- fied for one hour using 40% v/v ethylene glycol, 18% w/v Ficoll-70 and 0.5 M sucrose as the cryoprotectant. We recorded the numbers of surviving embryos from the control and experimental groups and their development until the blastocyst stage. Results were analyzed using the chi-square test.
RESULTS: A significantly higher proportion of EC embryos (96.7%) from the control group developed to the blastocyst stage compared with LC embryos (57.5%, P<0.0001). Similarly, in the experimental group, a significantly higher percentage of vitrified EC embryos (69.4%) reached the blastocyst stage compared to vitrified LC embryos (27.1%, P<0.0001).
CONCLUSION: Vitrified EC embryos are more vitrification tolerant than LC embryos. Prese- lection of EC embryos may be used as a tool for selection of embryos that exhibit higher developmental competence after vitrification.
The use of dimethyl sulfoxide in contact lens disinfectants is a potential preventative strategy against contracting Acanthamoeba keratitis

Siddiqui R, Aqeel Y, Khan NA

Cont Lens Anterior Eye, 2016 Oct;39(5):389-93.
PMID: 27133448 DOI: 10.1016/j.clae.2016.04.004

Acanthamoeba castellanii is the causative agent of blinding keratitis. Though reported in non-contact lens wearers, it is most frequently associated with improper use of contact lens. For contact lens wearers, amoebae attachment to the lens is a critical first step, followed by amoebae binding to the corneal epithelial cells during extended lens wear. Acanthamoeba attachment to surfaces (biological or inert) and migration is an active process and occurs during the trophozoite stage. Thus retaining amoebae in the cyst stage (dormant form) offers an added preventative measure in impeding parasite traversal from the contact lens onto the cornea. Here, we showed that as low as 3% DMSO, abolished A. castellanii excystation. Based on the findings, it is proposed that DMSO should be included in the contact lens disinfectants as an added preventative strategy against contracting Acanthamoeba keratitis.
The role of genomic islands in Escherichia coli K1 interactions with intestinal and kidney epithelial cells

Yousuf FA, Rafiq S, Siddiqui R, Khan NA

Microb Pathog, 2016 Apr;93:145-51.
PMID: 26867478 DOI: 10.1016/j.micpath.2016.02.002

The completion of Escherichia coli K1 genome has identified several genomic islands that are present in meningitis-causing E. coli RS218 but absent in the non-pathogenic E. coli MG1655. In this study, the role of various genomic islands in E. coli K1 interactions with intestinal epithelial cells (Caco-2) and kidney epithelial cells (MA104) was determined. Using association assays, invasion assays, and intracellular survival assays, the findings revealed that the genomic island deletion mutants of RS218 related to P fimbriae, S fimbriae, F17-like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, protein secretion system (T1SS for hemolysin; T2SS; T5SS for antigen 43), Iro system and hmu system), invasins (CNF1, IbeA), toxins (α-hemolysin), K1 capsule biosynthesis, metabolism (d-serine catabolism, dihydroxyacetone, glycerol, and glyoxylate metabolism), prophage genes, showed reduced interactions with both cell types. Next, we determined the role of various genomic islands in E. coli K1 resistance to serum. When exposed to the normal human serum, the viability of the genomic island deletion mutants related to adhesins such as S fimbriae, P fimbriae, F17-like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, antigen 43 and T5SS for antigen 43, T2SS, and T1SS for hemolysin, Iro system and hmu system, prophage genes, metabolism (sugar metabolism and d-serine catabolism), K1 capsule biosynthesis, and invasins such as CNF1 was affected, suggesting their role in bacteremia. The characterization of these genomic islands should reveal mechanisms of E. coli K1 pathogenicity that could be of value as therapeutic targets.
The increasing importance of novel deep eutectic solvents as potential effective antimicrobials and other medicinal properties

Siddiqui R, Khodja A, Ibrahim T, Khamis M, Anwar A, Khan NA

World J Microbiol Biotechnol, 2023 Oct 04;39(12):330.
PMID: 37792153 DOI: 10.1007/s11274-023-03760-8

With the rise of antibiotic resistance globally, coupled with evolving and emerging infectious diseases, there is an urgent need for the development of novel antimicrobials. Deep eutectic solvents (DES) are a new generation of eutectic mixtures that depict promising attributes with several biological implications. DES exhibit unique properties such as low toxicity, biodegradability, and high thermal stability. Herein, the antimicrobial properties of DES and their mechanisms of action against a range of microorganisms, including bacteria, amoebae, fungi, viruses, and anti-cancer properties are reviewed. Overall, DES represent a promising class of novel antimicrobial agents as well as possessing other important biological attributes, however, future studies on DES are needed to investigate their underlying antimicrobial mechanism, as well as their in vivo effects, for use in the clinic and public at large.
Fulltext The impact of insecticides and plant extracts on the suppression of insect vector (Bemisia tabaci) of Mungbean yellow mosaic virus (MYMV)

Younas M, Zou H, Laraib T, Rajpoot NA, Khan NA, Zaidi AA, et al.

PLoS One, 2021;16(9):e0256449.
PMID: 34529693 DOI: 10.1371/journal.pone.0256449

Mungbean yellow mosaic virus (MYMV) is an important constraint in successful production of mungbean (Vigna radiata L.) in many countries, including Pakistan. The MYMV spreads by insect vector whitefly (Bemisia tabaci Gennadius). The use of resistant cultivars is the most effective management tactics for MYMV. Twenty mungbean varieties/lines were screened against insect vector of MYMV under field condition in the current study. Resistance levels for varieties/lines were assessed through visual scoring of typical disease symptoms. Furthermore, the impacts of two insecticides 'Imidacloprid' and 'Thiamethoxam' and two plant extracts, i.e., neem (Azadirachta indica), and Eucalyptus (Eucalyptus camaldulensis) were tested on the suppression of whitefly. Field screening indicated that none of the tested varieties/lines proved immune/highly resistant, while significant variations were recorded among varieties/lines for resistance level. All varieties/lines were systemically infected with MYMV. The varieties 'AARI-2006' and 'Mung-14043' were considered as resistant to MYMV based on visual symptoms and the lowest vector population. These varieties were followed by 'NM-2006' and 'NL-31', which proved as moderately resistant to MYMV. All remaining varieties/lines were grouped as moderately to highly susceptible to MYMV based on visual symptoms' scoring. These results revealed that existing mungbean germplasm do not possess high resistance level MYMV. However, the lines showing higher resistance in the current study must be exploited in breeding programs for the development of resistant mungbean varieties/lines against MYMV. Imidacloprid proved as the most effective insecticide at all concentrations to manage whitefly population. Therefore, use of the varieties with higher resistance level and spraying Imidacloprid could lower the incidence of MYMV.
Fulltext The effects of phosphanegold(I) thiolates on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype

Siddiqui R, Abjani F, Yeo CI, Tiekink ER, Khan NA

J Negat Results Biomed, 2017 Apr 03;16(1):6.
PMID: 28366172 DOI: 10.1186/s12952-017-0070-7

BACKGROUND: Gold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.
METHODS: Anti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.
RESULTS: The treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.
CONCLUSION: Being free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.
The effect of peptidic and non-peptidic proteasome inhibitors on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype

Siddiqui R, Saleem S, Khan NA

Exp Parasitol, 2016 Jun 18;168:16-24.
PMID: 27327524 DOI: 10.1016/j.exppara.2016.06.006

The treatment of Acanthamoeba infections remains problematic, suggesting that new targets and/or chemotherapeutic agents are needed. Bioassay-guided screening of drugs that are clinically-approved for non-communicable diseases against opportunistic eukaryotic pathogens is a viable strategy. With known targets and mode of action, such drugs can advance to clinical trials at a faster pace. Recently Bortezomib (proteasome inhibitor) has been approved by FDA in the treatment of multiple myeloma. As proteasomal pathways are well known regulators of a variety of eukaryotic cellular functions, the overall aim of the present study was to study the effects of peptidic and non-peptidic proteasome inhibitors on the biology and pathogenesis of Acanthamoeba castellanii of the T4 genotype, in vitro. Zymographic assays revealed that inhibition of proteasome had detrimental effects on the extracellular proteolytic activities of A. castellanii. Proteasome inhibition affected A. castellanii growth (using amoebistatic assays), but not viability of A. castellanii. Importantly, proteasome inhibitors affected encystation as determined by trophozoite transformation into the cyst form, as well as excystation, as determined by cyst transformation into the trophozoite form. The ability of proteasome inhibitor to block Acanthamoeba differentiation is significant, as it presents a major challenge in the successful treatment of Acanthamoeba infection. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic infections.
Fulltext The Development of Drugs against Acanthamoeba Infections

Siddiqui R, Aqeel Y, Khan NA

Antimicrob Agents Chemother, 2016 11;60(11):6441-6450.
PMID: 27600042 DOI: 10.1128/AAC.00686-16

For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.
Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial

Low BY, Liong ML, Yuen KH, Chee C, Leong WS, Chong WL, et al.

J Urol, 2008 Apr;179(4):1461-9.
PMID: 18295277 DOI: 10.1016/j.juro.2007.11.060

PURPOSE: We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms.
MATERIALS AND METHODS: A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine.
RESULTS: Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05).
CONCLUSIONS: Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.
Targeting cyst wall is an effective strategy in improving the efficacy of marketed contact lens disinfecting solutions against Acanthamoeba castellanii cysts

Abjani F, Khan NA, Yousuf FA, Siddiqui R

Cont Lens Anterior Eye, 2016 Jun;39(3):239-43.
PMID: 26675112 DOI: 10.1016/j.clae.2015.11.004

Acanthamoeba cysts are highly resistant to contact lens disinfecting solutions. Acanthamoeba cyst wall is partially made of 1,4 β-glucan (i.e., cellulose) and other complex polysaccharides making it a hardy shell that protects the resident amoeba. Here, we hypothesize that targeting the cyst wall structure in addition to antiamoebic compound would improve the efficacy of marketed contact lens disinfecting solutions. Using chlorhexidine as an antiamoebic compound and cellulase enzyme to disrupt cyst wall structure, the findings revealed that combination of both agents abolished viability of Acanthamoeba castellanii cysts and trophozoites. When tested alone, none of the agents nor contact lens disinfecting solutions completely destroyed A. castellanii cysts and trophozoites. The absence of cyst wall-degrading enzymes in marketed contact lens disinfecting solutions render them ineffective against Acanthamoeba cysts. It is concluded that the addition of cyst wall degrading molecules in contact lens disinfecting solutions will enhance their efficacy in decreasing the incidence of Acanthamoeba effectively.
Targeting Brain-Eating Amoebae Infections

Khan NA, Ong TYY, Siddiqui R

ACS Chem Neurosci, 2017 04 19;8(4):687-688.
PMID: 28225265 DOI: 10.1021/acschemneuro.7b00049

Brain infections due to Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri often lead to death. Despite differences in the preferential sites of infection in the brain, the mode of delivery of drugs is often intravenous. Here, we discuss targeted therapeutic approach to affect parasite viability without affecting the host cells, with an eye to improve formulation of drugs and/or administration of drugs against brain-eating amoebae.
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.

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