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Interactions of Aurein with Model Membranes and antimalarials

American Journal of Analytical Chemistry 2024年第2期15卷 72-98页

作者： Anaif M. Alhewaitey Nsoki Phambu Naif M. Alhawiti Department of Chemistry Tennessee State University Nashville USA Department of Chemistry University of Tabuk Tabuk Saudi Arabia CAHFS University of California Davis Davis USA

Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project is focused on studying the interactions of aurein with model biological membranes and antimalarials using Fourier Transform Infrared (FTIR), fluorescence, dynamic light scattering (DLS), atomic force microscopy (AFM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. FTIR data revealed conformational changes to the secondary structure of the peptide in the presence of the model membranes. The strongest interactions of aurein were found with DOPC and lipid raft systems. Fluorescence data revealed some differences in the mechanism of interaction between aurein and lipid rafts. Topographical analysis was performed using atomic force microscopy (AFM). AFM images of the peptide with its lipid rafts showed a change in surface roughness suggesting a different mechanism of interaction. DLS data in agreement with FTIR confirmed that aurein interacts differently with the lipid rafts. The results gathered from this study provided new insights on the interaction of aurein. On the other hand, drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with infectious disease. This study has examined the interaction of aurein with quinine, primaquine, and chloroquine. Significant interactions between aurein and antimalarials occured at a higher concentration of antimalarials. Interactions between aurein and anti-malarials reveal a strong interaction between aurein and primaquine. Interactions between aurein and quinine or chloroquine were found to be weak and negligible. FTIR, TGA, and DSC may be used in a complementary way to gain insights into the possible drug-drug interactions involving aurein. These studies are needed to initiate in vivo controlled interaction studies between antibiotics and anti

关键词： Aurein Fluorescence DPPC SPM cholesterol DPPC-SPM-CHOL Quinine antimalarials

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Diagnosis and management of malaria in the intensive care unit

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Journal of Intensive Medicine 2024年第1期4卷 3-15页

作者： George Akafity Nicholas Kumi Joyce Ashong Department of Research Monitoringand EvaluationCape Coast Teaching HospitalCape CoastGhana Intensive Care Unit Department of Critical Care and AnesthesiaCape Coast Teaching HospitalCape Coast Department of Paediatrics and Child Health Cape Coast Teaching HospitalCape CoastGhana

Malaria is responsible for approximately three-quarters of a million deaths in humans globally each year.Most of the morbidity and mortality reported are from Sub-Saharan Africa and Asia,where the disease is endemic.In non-endemic areas,malaria is the most common cause of imported infection and is associated with significant mortality despite recent advancements and investments in elimination programs.Severe malaria often requires intensive care unit admission and can be complicated by cerebral malaria,respiratory distress,acute kidney injury,bleeding complications,and co-infection.Intensive care management includes prompt diagnosis and early initiation of effective antimalarial therapy,recognition of complications,and appropriate supportive care.However,the lack of diagnostic capacities due to limited advances in equipment,personnel,and infrastructure presents a challenge to the effective diagnosis and management of malaria.This article reviews the clinical classification,diagnosis,and management of malaria as relevant to critical care clinicians,highlighting the role of diagnostic capacity,treatment options,and supportive care.

关键词： Malaria Intensive care unit Severe malaria Antimicrobial resistance antimalarials Artemisinin-based combination therapy

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Comparative effects of parenteral antimalarials in Swiss albino mice after chronic exposure to Plasmodium berghei

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Animal Models and Experimental Medicine 2018年第3期1卷 235-241页

作者： Sylvester Aghahowa Kenka Okolocha Department of Pharmacology and Toxicology University of Benin

Mice are considered to be a similar model to humans in the pathogenesis of malaria. This study evaluates the effect of parenteral antimalarials on the spleen and liver of Swiss albino mice after chronic exposure to Plasmodium berghei. After chronic exposure to P. berghei NK65 strain, the level of parasitemia was assessed.The mice were treated for 3 days using chloroquine(5 mg/kg), quinine(10 mg/kg),and artemether(2 mg/kg). The effect of chronic exposure and the pattern of recovery were evaluated. There was significant decrease in total body weight after chronic exposure to P. berghei(P antimalarials; this was more pronounced with artemether. A significant increase in liver and spleen weights due to P. berghei infection was seen. There was a recovery pattern due to decrease in liver and spleen weights following antimalarial administration, which was greatest with artemether(P < 0.05). Significant changes were more in parasitized, quinine and artemether groups(P < 0.05). There was a significant decrease in total spleen protein due to chloroquine but a decrease due to quinine and artemether(P < 0.05). No significant changes in liver and spleen albumin were observed after treatment. The highest parasite clearance was observed with artemether, followed by quinine. Five mice died after chronic exposure in all the groups prior to treatment. There was significant enlargement and discoloration of spleen and liver after chronic exposure. This study showed that artemether aided recovery of the liver and spleen better than quinine and chloroquine in albino mice after chronic exposure to P. berghei. This suggests there is potential for improvement in antimalarial therapy.

关键词： antimalarials mice Plasmodium berghei

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Profiling of seminal antioxidant indices and sperm quality in Plasmodium bergheiinduced malarial mice treated with Phyllanthus amarus

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Asian pacific Journal of Reproduction 2022年第2期11卷 84-92页

作者： Williams Oshiegbu Chinwendu Obogheneophruhe Elu Innocent Onyesom Department of Biochemistry Delta State UniversityAbrakaNigeria Department of Medical Biochemistry Delta State UniversityAbrakaNigeria

Objective:To evaluate the antiplasmodial activity of Phyllanthus(P.)amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice.Methods:A total of 36 adult mice were divided into six groups,with 6 mice each.Five groups were infected with Plasmodium(P.)berghei,and one group was left uninfeceted.Of the five infected groups,one group was left untreated,three groups were treated with varying doses(100,250 and 400 mg/kg)of P.amarus crude ethanol leaf extract orally for 4 days,and another group was treated with standard drug,artemether and lumefantrine(Lonart®DS).Antiplasmodial activity,seminal quality,some biochemical indices(neutral毩-glucosidase,fructose,and citric acid)in seminal plasma and seminal antioxidant markers(catalase,glutathione peroxidase,reduced glutathione,malondialdehyde,total antioxidant capacity,and acid phosphates)were determined.The mice were euthanized 3 days post treatment and semen was collected from the caudal epididymis and processed for analysis using documented methods and procedures.Results:Malarial infection led to oxidative stress,causing a significant decline in seminal quality(P<0.05).However,treatment with P.amarus crude ethanol leaf extract alleviated oxidative stress and significantly improved seminal quality.The improvement was dose-dependent and compared well with the standard drug,artemether and lumefantrine(Lonart®DS)treatment.Conclusions:The ethanol leaf extracts of P.amarus alleviate male reproductive capacity during malaria infection in murine model by enhancing antioxidant activities.

关键词： Malaria Sperm quality Phyllanthus amarus Seminal oxidative stress Seminal antioxidant markers Antioxidants Ethanol extracts antimalarials

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Regioselective Synthesis and Biological Evaluation of 1-Hydroxyl Modified Ailanthinone Derivatives as antimalarials

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Open Journal of Synthesis Theory and Applications 2013年第4期2卷 91-96页

作者： Mahendra D. Chordia William F. McCalmont Kirsten S. Smith Philip L. Smith Division of Experimental Therapeutics Walter Reed Army Institute of Research Silver Spring USA

The triterpene quassinoid ailanthinone is a structurally intricate natural product possessing highly potent antimalarial activity against multidrug resistance plasmodium parasites. Although the mechanism of action of ailanthinone is not completely understood, it is presumed to disrupt regular ribosomal functions by inhibiting parasite protein synthesis. Natural scarcity and low solubility of many quassinoids have impeded their development as potential clinical candidates, but exquisite potency of ailanthinone against Plasmodium remains compelling in the global fight against malaria. Herein, we report the highly selective synthesis of 1-hydroxyl derivatives of ailanthinone, including ester, carbonate, carbamate and sulfonate derivatives. The key feature of the synthesis is a one-step regioselective modification of the 1-hydroxyl group in favor of two other hydroxyl groups at C12 and C13. Derivatives were obtained via direct reaction with acyl/sulfonyl chlorides in the presence of a tertiary amine base without any protection-deprotection. In vitro antimalarial evaluations of these derivatives were compared with chloroquine and mefloquine against the Plasmodium falciparum clones, D6, W2, and TM91C235. The results demonstrate that modification of the 1-hydroxyl group is achievable, and the antimalarial activity of these derivatives relative to the parent product is significantly retained, thus paving the way for synthesis of derivatives with improved biological availability and/or increased potency.

关键词： antimalarials Ailanthinone Triterpenoids Quassinoid Plasmodium Falciparum Multidrug Resistance

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Artemisinin anti-malarial drugs in China

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Acta Pharmaceutica Sinica B 2016年第2期6卷 115-124页

作者： Zongru Guo Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine,together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970 s, a special period in China, by hundreds of scientists all together under the "whole nation"system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements.

关键词： antimalarials Artemisinin Artemether Artesunate Dihydroartemisinin

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Development of antimalarial drugs and their application in China: a historical review

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Infectious Diseases of Poverty 2014年第1期3卷 70-79页

作者： Chang Chen National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention200025 ShanghaiChina

This historical review covers antimalarials developed in China,which include artemisinin,artemether,artesunate,and dihydroartemisinin,as well as other synthetic drugs such as piperaquine,pyronaridine,benflumetol(lumefantrine),and naphthoquine.The curative effects of these antimalarials in the treatment of falciparum malaria,including chloroquine-resistant strain,are especially discussed.Following the World Health Organization(WHO)recommended artemisinin-based combination therapy(ACT),different combinations of artemisinin,or its derivative,along with another antimalarial drug were orally used to treat Plasmodium falciparum infections.The recrudescence rates were low,gametocyte carriers lessened,and the curative rate increased remarkably.The combination therapy effectively deferred the emergence of drug resistance in the parasite.The regulation“The guidelines and regimens for the use of antimalarial drugs in China”was issued to guide rational application and standardize malaria treatment in the country.As the recommended first-line drug to treat falciparum malaria in the world,ACT was adopted in the regulation.In response to the global initiative of malaria eradication proposed by the UN Millennium Development Goals(MDGs),the Chinese government has set a target to eliminate malaria by 2020.

关键词： antimalarials Malaria Treatment China

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Chemotherapy and drug resistance status of malaria parasite in northeast India

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Asian Pacific Journal of Tropical Medicine 2013年第7期6卷 583-588页

作者： Diganta Goswami Indra Baruah Sunil Dhiman Bipul Rabha Vijay Veer Lokendra Singh Dhirendra Kumar Sharma Division of Medical Entomology Defence Research LaboratoryTezpurAssam.India Directorate of Life Sciences DRDO HQNew DelhiIndia Department of Zoology Gauhati UniversityGuwahatiIndia

India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for>10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.

关键词： Malaria Chemotherapy antimalarials Drug resistance

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A Randomized,Controlled Trial of Artemisinin-piperaquine vs Dihydroartemisinin-piperaquine Phosphate in Treatment of Falciparum Malaria

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Chinese Journal of Integrative Medicine 2009年第3期15卷 189-192页

作者： Trieu Nguyen Trung 谈博 Dang Van Phuc 宋健平 Institute of Malariology Parasitology and Entomology-Qui Nhon Ministry of Health Research Center for Qinghao(Artemisia annual L.) Guangzhou University of Chinese Medicine

Objective:The study aimed to evaluate and compare the efficacy and safety of dihydroartemisininpiperaquine phosphate(Artekin) and artemisinin-piperaquine(Artequick) in the treatment of uncomplicated falciparum malaria.Methods:A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups:52 cases in the Artequick group,and 51 cases in the Artekin group.The patients in the Artequick group were administered with Artequick,twice in 24 h,whereas the patients in the Ar...

关键词： Plasmodium falciparum malaria artemisinin piperaquine antimalarials randomized controlled trial

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Availability of Antimalarial Medicines in Community Pharmacies of Lusaka District, Zambia: Implications on Compliance to Malaria Treatment Guidelines

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Pharmacology & Pharmacy 2023年第4期14卷 85-97页

作者： Tadious Chimombe Steward Mudenda Stephen Bwalya Tamara N’gona Christabel Nang’andu Hikaambo Webrod Mufwambi Audrey Hamachila Simon Nkowani Busiku Hamainza Department of Pharmacy School of Health Sciences University of Zambia Lusaka Zambia National Malaria Elimination Centre Ministry of Health Lusaka Zambia

Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availability of antimalarial medicines is one of the key interventions of malaria management. This study assessed the availability of antimalarial medicines in community pharmacies in Lusaka district, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 210 community pharmacies from September to November 2022 using a well-structured checklist in selected areas of Lusaka district. The availability was verified by a physical check of the product. The checklist contained the medicines listed both in the guidelines for diagnosis and treatment of malaria in Zambia as well as in the World Health Organization (WHO) malaria treatment guidelines. Results: This study found that all antimalarials listed in the local treatment guidelines for malaria were available in community pharmacies, though with the varying distribution. Of the 210 community pharmacies, 209 (99.5%) had artemether/lumefantrine in stock. The lowest available antimalarial was quinine/clindamycin, which was only available in 3 (1.4%) of the outlets. Conversely, 3 out of 16 (18.8%) antimalarials that were available in community pharmacies were not listed in the local treatment guidelines of malaria in Zambia, despite being listed in the WHO malaria treatment guidelines. This translated into a compliance level of 81.2% based on the local malaria treatment guidelines. Conclusion: This study concluded that antimalarials were available for all categories of malaria management in community pharmacies, though with a varying distribution. The presence of antimalarials not listed in the Zambian treatment guidelines is of public health concern which may have an impact on antimicrobial resistance in the future.

关键词： antimalarials Antimalarial Medicines Availability Community Pharmacies Zambia

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