ABSTRACT
Leishmania major (L. major) is a protozoan parasite that causes cutaneous leishmaniasis. About 12 million people are currently infected with an annual incidence of 1.3 million cases. The purpose of this study was to synthesize a small library of novel thiophene derivatives, and evaluate its parasitic activity, and potential mechanism of action (MOA). We developed a structureâ»activity relationship (SAR) study of the thiophene molecule 5A. Overall, eight thiophene derivatives of 5A were synthesized and purified by silica gel column chromatography. Of these eight analogs, the molecule 5D showed the highest in vitro activity against Leishmania major promastigotes (EC50 0.09 ± 0.02 µM), with an inhibition of the proliferation of intracellular amastigotes higher than 75% at only 0.63 µM and an excellent selective index. Moreover, the effect of 5D on L. major promastigotes was associated with generation of reactive oxygen species (ROS), and in silico docking studies suggested that 5D may play a role in inhibiting trypanothione reductase. In summary, the combined SAR study and the in vitro evaluation of 5A derivatives allowed the identification of the novel molecule 5D, which exhibited potent in vitro anti-leishmanial activity resulting in ROS production leading to cell death with no significant cytotoxicity towards mammalian cells.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Leishmania major/drug effects , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Small Molecule Libraries/chemical synthesis , Thiophenes/chemical synthesis , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Cell Line , Drug Evaluation, Preclinical , Leishmania major/metabolism , Leishmaniasis, Cutaneous/drug therapy , Mice , Mice, Inbred BALB C , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Protozoan Proteins/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Structure-Activity Relationship , Thiophenes/chemistry , Thiophenes/pharmacologyABSTRACT
ABSTRACT: Anthropometric measurements are used to assess growth of children which is affected by different biological and environmental factors. The importance of the period after the first 1000 days of life has been identified in the attempt to restore normal growth and body functions. The objectives of this study are to assess the growth and nutritional status of school children in Khartoum locality, Khartoum State, Sudan and to verify socioeconomic status and sex as factors influencing growth of children. This is a cross-sectional school-based study including 390 children, males and females, of ages between 5-12 years (60-44 months) from private and public schools. Anthropometric measurements were taken by standardized techniques and calibration and age was calculated in months. Using WHO's Anthroplus and SPSS, BMI for age z-scores (BAZ), height for age z-scores (HAZ) and weight for age z-scores (WAZ) were calculated and descriptive and analytical statistics were generated and tested. According to the WHO reference, 3.3% of the studied children were severely thin, 6.9% were thin, 8.7% were overweight and 6.7% were obese. The children showed low mean BAZ and a similar mean HAZ compare to WHO reference. Children in public schools showed significantly lower means compared to those in the private schools in all indicators; BAZ, HAZ and WAZ. Girls showed significantly higher means compared to boys with a significant occurrence of overweight and obesity among girls especially in private schools. Weak negative correlation between HAZ and age and weak positive correlation between HAZ and BAZ were detected. Further studies and tailored interventions are recommended.
Subject(s)
Body Height , Nutritional Status , Body Mass Index , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , SudanABSTRACT
The aim of this study was to determine the percentage of women who give birth to low birth weight (LBW) children and to study the association of the different risk factors with LBW in three of large hospitals in Khartoum State, Sudan. This was a cross sectional study of 381 women. Three groups: 151, 130 and 100 women, who gave birth to live children, were selected from Alsuadi Teaching Hospital, Khartoum Teaching Hospital and Alribat University Hospital, respectively. Data were collected through structured interviews and the birth weights were recorded as measured by midwives. Uni-Multi variate analysis of the data was performed using SPSS 19. Permissions were taken from hospital administration and the participants before the conduction of the research. 13% of live born children were of low birth weight. The main risk factors for low birth weight in the study were the lack of adequate education (OR= 1.9) gestational age (OR= 5.5), type of pregnancy (OR= 9.6), presence of hypertension (OR= 3.6), renal disease (OR= 2.1), bleeding during pregnancy (OR= 6.1) and presence of moderate or severe anemia (OR= 3.19). While Adequacy of antenatal care (ANC) visits, presence of diabetes mellitus during pregnancy, smoking and malaria in the first three trimesters, presence of previous children and spacing were all found to be statistically not significant risk factors. Many of the risk factors are modifiable and can be prevented by improvement of the health care during pregnancy.
