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Anti-amoebic effects of synthetic acridine-9(10H)-one against brain-eating amoebae

Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.

Acta Trop, 2023 Mar;239:106824.
PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824

Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
Fulltext Phytochemical characterization and anti-arthritic potential of Croton bonplandianus leaves extract: In-vivo and in-silico approach

Javed E, Khan HM, Shahzad Q, Shahzad Y, Yasin H, Ul-Haq Z, et al.

Saudi Pharm J, 2023 Dec;31(12):101860.
PMID: 38192284 DOI: 10.1016/j.jsps.2023.101860

Croton bonplandianus, a natural source traditionally used for treating various illnesses, including rheumatoid arthritis, was evaluated in this study. The effects of ethanolic extracts (CBEE) and aqueous fractions (CBAF) of C. bonplandianus leaves on arthritis-induced inflammation were studied using an albino rat model of inflammation induced by Freund's complete adjuvant. Eight test groups (n = 5 per group) and one vehicle control were used to evaluate the antiarthritic effects of different doses of CBEE and CBAF (125 mg.kg-1, 250 mg.kg-1, and 500 mg.kg-1) on days 5, 10, 15, and 20 compared to arthritic and vehicle controls. Arthritis severity was assessed using macroscopic arthritis grading, histological analysis, body weights, and paw thickness. CBEE and CBAF were found to reduce the prevalence of arthritis, increase body weight, and decrease paw inflammation compared to the vehicle control group by the 23rd day. In addition, they showed no effect on biochemical parameters, but a significant difference (p
Fulltext Are pharmacists on the front lines of the opioid epidemic? A cross-sectional study of the practices and competencies of community and hospital pharmacists in Punjab, Pakistan

Mubarak N, Zahid T, Rana FR, Ijaz UE, Shabbir A, Manzoor M, et al.

BMJ Open, 2023 Nov 21;13(11):e079507.
PMID: 37989383 DOI: 10.1136/bmjopen-2023-079507

INTRODUCTION: Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues.
STUDY DESIGN: A cross-sectional study, conducted across Punjab, Pakistan.
METHOD: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists.
RESULTS: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'.
CONCLUSION: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce.

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