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antimalarial activity

Ming Ni, Jin-Gang He, Hai-Yun Zhou, Xiao-Jia Lu, Yuan-Lang Hu, Li Mao, Fang Wang, Jian-Guo Chen, Zhuang-Li Hu
Mefloquine (MFQ) is widely used for the treatment of malaria clinically. Apart from antimalarial effect, psychiatric side effects such as depression and anxiety of MFQ have been reported. Interestingly, MFQ is also known as a broad-spectrum pannexin-1 (Panx1) inhibitor. Panx1 is a new gap junction channel expressed in the brain which mediates efflux of adenosine triphosphate (ATP). Although exogenous ATP has been known to produce a potential antidepressant-like effect, little is known about the role of Panx1 in pathophysiology of depression, especially the depression induced by administration of MFQ...
December 5, 2017: Neuropharmacology
Kristina Pavić, Ivana Perković, Šárka Pospíšilová, Marta Machado, Diana Fontinha, Miguel Prudêncio, Josef Jampilek, Aidan Coffey, Lorraine Endersen, Hrvoje Rimac, Branka Zorc
Four series of primaquine (PQ) derivatives were screened for antitubercular and antiplasmodial activity: amides 1a-k, ureas 2a-s, semicarbazides 3a-c and bis-ureas 4a-u. Antimycobacterial activity of PQ derivatives against Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. avium subsp. paratuberculosis (MAP) were evaluated in vitro and compared with PQ and the standard antitubercular drugs. In general, the PQ derivatives showed higher potency than the parent compound. Most of the compounds of series 1 and 2 showed high activity against MAP, comparable or even higher than the relevant drug ciprofloxacin, and weak or no activity against MTB and MAC...
December 2, 2017: European Journal of Medicinal Chemistry
Raghupathi Neelarapu, Jordany R Maignan, Cynthia L Lichorowic, Andrii Monastyrskyi, Tina S Mutka, Alexis N LaCrue, Lynn D Blake, Debora Casandra, Sherwin Mashkouri, Jeremy N Burrows, Paul A Willis, Dennis E Kyle, Roman Manetsch
Malaria deaths have been decreasing over the last 10-15 years, with global mortality rates having fallen by 47% since 2000. While the World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) to combat malaria, the emergence of artemisinin resistant strains underscores the need to develop new antimalarial drugs. Recent in vivo efficacy improvements of the historical antimalarial ICI 56,780 have been reported, however with the poor solubility and rapid development of resistance, this compound requires further optimization...
December 7, 2017: Journal of Medicinal Chemistry
Nele Seemann, Andrea Welling, Ingo Rustenbeck
The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a KATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca2+ channel activity, cytosolic Ca2+ concentration ([Ca2+]i) and insulin secretion...
December 2, 2017: Molecular and Cellular Endocrinology
Sana Tariq, K Somakala, Mohd Amir
Quinoxaline, a fused heterocycle of benzene and pyrazine rings has gained considerable attention in the field of contemporary medicinal chemistry. The moiety is of substantial importance because of its wide array of pharmacological activities viz. anti-cancer, antimalarial, anti-inflammatory, antimicrobial, anti-HIV etc. Diversely substituted quinoxalines are important therapeutic agents in the pharmaceutical industry. This review focusses on the quinoxaline derivatives developed during the last decennial period and their biomedical applications...
November 24, 2017: European Journal of Medicinal Chemistry
Katherine Plewes, Gareth D H Turner, Arjen M Dondorp
PURPOSE OF REVIEW: Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research. RECENT FINDINGS: Cerebral malaria and AKI are serious and well recognized complications of severe malaria...
December 4, 2017: Current Opinion in Infectious Diseases
Ali Ramazani, Behnam Khosravani, Jafar Taran, Ali Ramazani
Because of expanding resistance to efficient and affordable antimalarial drugs like chloroquine, the search is continuing for more effective drugs against this disease. In-vitro antiplasmodial activity and cytotoxicity of α-(acyloxy)-α-(quinolin-4-yl) acetamides on Plasmodiumfalciparum and structure-activity relationships of this new class of Passerini adducts is described. The in-vitro antiplasmodial activity of compounds was tested against chloroquine sensitive 3D7 strain. Toxicity of active compounds was investigated on HepG2 cell line...
2017: Iranian Journal of Pharmaceutical Research: IJPR
Maryam Alborz, Aliasghar Jarrahpour, Roya Pournejati, Hamid Reza Karbalaei-Heidari, Véronique Sinou, Christine Latour, Jean Michel Brunel, Hashem Sharghi, Mahdi Aberi, Edward Turos, Lukasz Wojtas
Highly diastereoselective synthesis of some novel benzothiazole-substituted β-lactam hybrids was achieved starting from (benzo[d]thiazol-2-yl)phenol as an available precursor. This is the first time (benzo[d]thiazol-2-yl)phenoxyacetic acid has been used as ketene source in synthesizing monocyclic 2-azetidinones. These compounds were evaluated for their antimicrobial activities against a large panel of Gram-positive and Gram-negative bacterial strains and moderate activities were encountered. Antimalarial data revealed that adding methoxyphenyl or ethoxyphenyl group on the β-lactam ring makes compounds that are more potent...
November 21, 2017: European Journal of Medicinal Chemistry
Nicoletta Basilico, Silvia Parapini, Anna Sparatore, Sergio Romeo, Paola Misiano, Livia Vivas, Vanessa Yardley, Simon L Croft, Annette Habluetzel, Leonardo Lucantoni, Laurent Renia, Bruce Russell, Rossarin Suwanarusk, Francois Nosten, Giulio Dondio, Chiara Bigogno, Daniela Jabes, Donatella Taramelli
Natural products are a prolific source for the identification of new biologically active compounds. In the present work, we studied the in vitro and in vivo antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4-aminoquinoline and a quinolizidine moiety derived from lupinine (Lupinus luteus). The aim was to find a compound endowed with the target product profile-1 (TCP-1: molecules that clear asexual blood-stage parasitaemia), proposed by the Medicine for Malaria Venture to accomplish the goal of malaria elimination/eradication...
December 1, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Robert L Clark, Tammye L Edwards, Monica Longo, Joseph Kinney, Don K Walker, Jon Rhodes, Sally A Clode, Thomas Rückle, Timothy Wells, Nicole Andenmatten, Anna Christine Huber
BACKGROUND: Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety. METHODS: As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos...
November 28, 2017: Birth Defects Research
Mokhitli Morake, Dina Coertzen, Andile Ngwane, Johannes Wentzel, Ho Ning Wong, Frans Smit, Lyn-Marie Birkholtz, Ray-Dean Petersen, Bienyameen Baker, Ian Wiid, David N'Da, Richard K Haynes
In order to evaluate the feasibility of developing drugs that may be active against both malaria and tuberculosis (TB) by utilizing in part putative cholesterol transporters in the causative pathogens and through enhancement of passive diffusion in granulomatous TB, artemisinin-cholesterol conjugates were synthesized by connecting the component molecules through various linkers. The compounds were screened in vitro against Plasmodium falciparum (Pf) and Mycobacterium tuberculosis (Mtb). Antimalarial activities (IC50) against Pf drug sensitive NF54, and drug resistant K1 and W2 strains ranged from 0...
November 28, 2017: ChemMedChem
Mofolusho O Falade, Favour Komoni, Roseangela I Nwuba
Enhanced antimalarial activity of plant extracts used for treatment of malaria in endemic areas is attributed to partial immunity gained by prior infection. This suggests synergy between immunity and extract activity in treatment. Testing this hypothesis, rodent malaria was used to determine efficacy of Lophira alata leaf extracts in treating malaria in prior infected mice. One round of P. berghei infection and Pyrimethamine drug-cure was used to establish partial immunity in mice. Previously Exposed Mice (PEM) and Previously Unexposed Mice (PUM) mice challenged with P...
November 30, 2017: Drug Research
Mukesh C Joshi, John Okombo, Samkele Nsumiwa, Jeffrey Ndove, Dale Taylor, Lubbe Wiesner, Roger Hunter, Kelly Chibale, Timothy J Egan
Emergence of drug resistant Plasmodium falciparum including artemisinin-tolerant parasites highlights the need for new antimalarials. We have previously shown that dibemequines, 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains, are efficacious. In this study, analogues in which the terminal phenyl group of the dibemethin was replaced with a 2-pyridyl group and the 4-amino-7-chloroquinoline was either maintained or replaced with a 4-aminoquinoline-7-carbonitrile were synthesized in an effort to improve drug-likeness...
November 29, 2017: Journal of Medicinal Chemistry
Alicia Moreno-Sabater, Jean Louis Pérignon, Dominique Mazier, Catherine Lavazec, Valerie Soulard
Efforts on malaria drug discovery are expected to increase in the coming years to achieve malaria eradication. Owing to the increasing number of new potential candidates together with the actual limitations of the primate models, humanized mouse models infected with human Plasmodium spp. (HmHP) now appear as an alternative to the primate model. Areas covered: The authors review the progress obtained in the HmHP in the last two decades, with a special emphasis of their input on the drug discovery pathway. The authors discuss the methodologies and strategies used in these models to obtain an accurate assessment of the compound activity and a reliable prediction of the human efficacious regimen...
November 28, 2017: Expert Opinion on Drug Discovery
Yuta Endo, Taku Kasahara, Kenicni Harada, Miwa Kubo, Tadahiro Etoh, Masami Ishibashi, Aki Ishiyama, Masato Iwatsuki, Kazuhiko Otoguro, Satoshi O Mura, Gokithi Akisue, Tomoya Hirano, Hiroyuki Kagechika, Yoshiyasu Fukuyama, Ayumi Ohsaki
Twelve new furanocassane diterpenoids, sucupiranins A-L (1-12), and three known compounds (13-15) were isolated from the seeds of Bowdichia virgilioides. The structures of the compounds were elucidated via 1H and 13C NMR analysis, including 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray crystallographic analysis. The absolute configurations were defined using their electronic circular dichroism (ECD) spectra by applying the exciton chirality method to the bis-p-bromobenzoate of compound 13...
November 28, 2017: Journal of Natural Products
Emil Yu Yamansarov, Dmitri V Kazakov, Natal'ya I Medvedeva, Elmira F Khusnutdinova, Oxana B Kazakova, Yuliya V Legostaeva, Gumer Yu Ishmuratov, Le Mai Huong, Tran Thi Hong Ha, Do Thi Huong, Kyrill Yu Suponitsky
A series of new steroidal peroxides - 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes based on deoxycholic acid were prepared via the reactions of the Griesbaum coozonolysis and peroxycondensation, respectively. 1,2,4-Trioxolanes were synthesized by the interaction of methyl O-methyl-3-oximino-12α-acetoxy-deoxycholate with CF3C(O)CH3 or CF3C(O)Ph and O3 as the mixtures of four possible stereoisomers at ratios of 1:2:2:1 and in yields of 50% and 38%, respectively. The major diastereomer of methyl 12α-acetoxy-5β-cholan-24-oate-3-spiro-5'-(3'-methyl-3'-trifluoromethyl-1',2',4'-trioxolane) was isolated via crystallization of a mixture of stereoisomers from hexane and its (3S,3'R)-configuration was determined using X-ray crystallographic analysis...
November 24, 2017: Steroids
Sarot Cheenpracha, Pannakorn Boapun, Thunwadee Limtharakul Née Ritthiwigrom, Surat Laphookhieo, Stephen G Pyne
The phytochemical investigation of an alkaloidal extract of Holarrhena pubescens roots led to the isolation and identification of a new pregnene-type alkaloid, mokluangin D (1), together with nine known steroidal alkaloids (2-10). The structure of the new metabolite was determined on the basis of spectroscopic analyses including 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 3 and 4 showed potent antimalarial activity against Plasmodium falciparum K1 stain with IC50 values of 1.2 and 2.0 μM, respectively, and showed weak cytotoxic activity against the NCI-H187 cell line with IC50 values of 27...
November 24, 2017: Natural Product Research
Abdoul Karim Ouattara, Pouiré Yameogo, Lassina Traore, Birama Diarra, Maléki Assih, Tegwindé Rébéca Compaore, Dorcas Obiri-Yeboah, Serge Théophile Soubeiga, Florencia Wendkuuni Djigma, Jacques Simpore
BACKGROUND: It is now well-known that some antimalarials such as primaquine may induce severe hemolytic anemia in people with G-6-PD deficiency. Antimalarial drug prescriptions must, therefore take into account the patient's G-6-PD status in malaria endemic areas such as Burkina Faso, where the prevalence of this genetic abnormality is relatively high. Although great clinical heterogeneity is observed depending on the molecular nature of the deficiency and the residual enzyme activity in the red blood cell, there is very poor data on the prevalence of G-6-PD deficiency and the distribution of involved genetic variants in Burkina Faso...
November 23, 2017: BMC Medical Genetics
Suelem D Ramalho, Meri Emili F Pinto, Douglas Ferreira, Vanderlan S Bolzani
A comprehensive overview of natural orbitides isolated from Euphorbiaceae species and their most relevant biological activities are presented. Euphorbiaceae is a large and diverse family, which comprises about 300 genera, and is known as an important source of medicines and toxins. Several classes of secondary metabolites have been described for this taxon, however, orbitides have been broadly reported in Jatropha and Croton genera. Additionally, the latex is documented as the main source of orbitides in this family...
November 23, 2017: Planta Medica
Pius S Fasinu, Vamshi K Manda, Olivia R Dale, Nosa O Egiebor, Larry A Walker, Shabana I Khan
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells...
November 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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