Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

FATAL RATES OF MALARIA PATIENTS IN THE RUSSIAN FEDERATION IN 2020

The article presents data on 7 deaths of patients with malaria (Plasmodium falciparum) in 2020 in the Russian Federation, errors in the epidemiological, clinical and laboratory diagnostics of malaria. The use of preventive measures and effective drugs, adherence to the Protocol for the treatment of patients with malaria of various types, improving the knowledge of medical personnel of medical and preventive medical organizations are especially necessary during a pandemic of a new coronavirus infection for the timely differential diagnosis of diseases. Key words: malaria, clinical diagnostics, treatment, deaths.

Artemether and imatinib combination therapy against malaria infection

Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization (WHO) as the first and second line of treatment for uncomplicated malaria caused by P. falciparum, as well as for chloroquine-resistant P. vivax malaria. Despite the large number of antimalarial drugs, there is no any ideal drug, since each individual combination of drugs or monotherapy have their own limitations, ranging from their triple (activity) in relation to certain forms of the development of Plasmodium in the human body, side effects, toxicity and resistance. During the course of the study carried out, the most promising compound-candidate was selected – imatinib, which is currently used as targeted therapy for a number of oncological diseases. The objective of this work is to evaluate the efficacy of the combined use of imatinib and artemether in vivo studies on the human malarial model – the rodent malaria parasites Plasmodium berghei. Dut to the optimally selected treatment scheme, it was possible to reduce the dosage of imatinib twice – to 0,25 mg/kg, and that of artemether three times – to 33 mg/kg. The use of this scheme made it possible to considerably reduce the toxic effect of these drugs due to the potentiation of antimalarial effect. Key words: malaria, drug resistance, telomerase inhibitors, imatinib, chemotherapy of malaria

Determinants of the epidemic process of malaria

Malaria was found in the regions of the republic and in Baku. Natural and artificial reservoirs are a favorable breeding ground for mosquitoes. Environmental factors influence the activity and the increase and decrease in the number of mosquitoes. The mosquito activity is affected by the smells of sick people. The epidemic process of malaria is influenced by natural, social and biological factors. The epidemiological control of malaria in the country has led to the elimination of the disease. Key words: malaria, epidemic process, source of infection, mosquitoes, determinants: biological, natural and social factors, epidemiological surveillance, elimination

In vivo effectiveness of the inhibitors of telomerase against malaria parasites

One of the most dangerous causative agents of malaria is Plasmodium falciparum, transmitted by various Anopheline mosquitoes. Due to widespread drug resistance to practically all antimalarials, novel and effective drugs to manage this important disease are urgently required. In this study we evaluated the antimalarial activity of a series of 14 compounds from the inhibitors of the telomerase group. For in vivo studies we used P. berghei strain NK 65 in white unbread mice. The most antimalarial activity was shown by Imatinib, Phosphazide and Imetelstat. We found that Imatinib is the most potent compound and therefore can serve as a potential lead for the development of new antimalarial drug. Key words: malaria, drug resistance, inhibitors of telomerase, imatinib, chemotherapy of malaria

“STUDY OF CLINICAL, BIOCHEMICAL AND HEMATOLOGICAL PROFILE IN MALARIA PATIENTS”

Points and destinations of current examination were to contemplate the clinical, biochemical and hematological profiles in smear positive jungle fever patients and its connection to prompt result of patient. To investigate the biochemical and hematological awkward nature and its connection with clinical introduction and kind of malarial parasites. To explain the connection of hematological and biochemical changes in kids contaminated with jungle fever and their effect on prompt result of patients. All patients conceded with a finding of intestinal sickness in branch of Pediatrics at Shri Mahant Indiresh Hospital, Dehradun, Uttarakhand amid the examination time of 10 January 2018 to 12 December 2018. Test measure was 109 cases. The investigation was done in the wake of getting a definite history, complete general physical examination and fundamental examination. The patients were exposed to pertinent examinations. The information with respect to understanding points of interest, analysis and examinations is gathered in an uncommonly structured case recording structure and exchanged to an ace graph exposed to measurable techniques like mean, standard deviation, extent, rate computation and wherever fundamental chi square test for extent are utilized. Complete 106 patients were enlisted in study. Complexities of PF (N=32): Jaundice 17%, extreme pallor 22%, thrombocytopenia 28%, leukopenia in 24%, hyponatremia in 30 %, cerebral intestinal sickness in 17% and hyperkalemia in 16%. Intricacies of PV (N=66): Jaundice 21%, serious iron deficiency 21%, thrombocytopenia 19%, leukopenia in 12%, hyponatremia in 45.8%, hyperkalemia in 10%, cerebral intestinal sickness in 11.7% and hypoglycemia in 4.02%. Key words: Malaria, Smear positive malaria, RFT, LFT, Hemogram

Prevalence of Malaria Parasites Among Blood Donors in Selected Hospitals of Dhaka City

Blood serves as a vehicle for transmission of blood-borne pathogens and transfusion-associated malaria is a potentially serious complication. The present study was conducted to determine the prevalence of Malaria parasites in blood donors. Total of 400 blood donors were selected from Transfusion Medicine Department of two teaching institutes, Bangabandhu Sheikh Mujib Medical University (BSMMU) and National Institute of Diseases of Chest and Hospital (NIDCH), Dhaka between the period of 1st January and 30th April 2003. The blood samples were examined under microscope by thick film in the laboratory of Institute of Epidemiology, Disease Control & Research (IEDCR), Dhaka. The socio-demographic characteristics of the study subjects show that 304 (76%) blood donors were males and 96 (24%) of them were females. The malaria parasites were found in 3 (0.76%) donors out of 400 donors. From 400 donors, 52 (13%) donors had the history of residence/ travel in malaria zone and 348 (87%) had no such history. The 8 (15%) out of 52 who had the history of residence/ travel in malaria zone had previous history of malaria and had taken anti-malarial drug. It can be concluded from the present study that there is some risk of transmission of malaria parasites in blood transfusion among the voluntary and professional blood donors in Bangladesh. Key words: Malaria parasites; Blood donors; Thick film. DOI: 10.3329/jdmc.v17i2.6590J Dhaka Med Coll. 2008; 17(2) : 94-97