Exploring antimalarial potential: Conjugating organometallic moieties with organic fragments for enhanced efficacy.

In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.

A disfiguring neglected tropical disease sweeps war-torn Yemen: a community-based study of prevalence and risk factors of cutaneous leishmaniasis among rural communities in the western highlands.

BACKGROUND: Cutaneous leishmaniasis (CL) is a major health problem in Yemen and is endemic in many rural areas across the country. METHODS: A community-based cross-sectional survey followed by unmatched case-control comparisons was conducted among 612 participants in Utmah district, western Yemen. A total of 223 participants were included in the case-control analysis to identify the significant risk factors. Skin scrapping samples were examined by microscopy and internal transcribed spacer 1 nested polymerase chain reaction. RESULTS: Overall, 33% (202/612) of the participants had active skin lesions and/or scars that met the clinical criteria for CL. A total of 90 (14.7%) participants had suspected active CL lesions; however, a prevalence of 8.7% (53/612) was obtained based on molecular and parasitological examination, with Leishmania tropica being the only causative agent identified. Multivariable logistic regression analyses showed that being ≤10 y old, being female, living in houses with cracked walls, living in the presence of other family members with typical ulcerating skin diseases and sleeping outside were factors significantly associated with an increased likelihood of having CL. Moreover, keeping livestock on the ground floor of the house was significantly associated with a decreased likelihood of having CL. CONCLUSION: The study reveals an alarmingly high prevalence of CL among the studied population. Therefore there is an urgent need for effective control measures and improved treatment efforts against this devastating disease.

Plasmodium knowlesi malaria an emerging public health problem in Hulu Selangor, Selangor, Malaysia (2009-2013): epidemiologic and entomologic analysis.

BACKGROUND: While transmission of the human Plasmodium species has declined, a significant increase in Plasmodium knowlesi/Plasmodium malariae cases was reported in Hulu Selangor, Selangor, Malaysia. Thus, a study was undertaken to determine the epidemiology and the vectors involved in the transmission of knowlesi malaria. METHODS: Cases of knowlesi/malariae malaria in the Hulu Selangor district were retrospectively reviewed and analyzed from 2009 to 2013. Mosquitoes were collected from areas where cases occurred in order to determine the vectors. Leucosphyrus group of mosquitoes were genetically characterized targeting the nuclear internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c oxidase subunit I (CO1). In addition, temporal and spatial analyses were carried out for human cases and vectors. RESULTS: Of the 100 microscopy diagnosed P. knowlesi/P. malariae cases over the 5 year period in the Hulu Selangor district, there was predominance of P. knowlesi/P. malariae cases among the young adults (ages 20-39 years; 67 cases; 67%). The majority of the infected people were involved in occupations related to agriculture and forestry (51; 51%). No death was recorded in all these cases.Five hundred and thirty five mosquitoes belonging to 14 species were obtained during the study. Anopheles maculatus was the predominant species (49.5%) followed by Anopheles letifer (13.1%) and Anopheles introlatus (11.6%). Molecular and phylogenetic analysis confirmed the species of the Leucosphyrus group to be An. introlatus. In the present study, only An. introlatus was positive for oocysts. Kernel Density analysis showed that P. knowlesi hotspot areas overlapped with areas where the infected An. introlatus was discovered. This further strengthens the hypothesis that An. introlatusis is the vector for P. knowlesi in the Hulu Selangor district.Unless more information is obtained on the vectors as well as macaque involved in the transmission, it will be difficult to plan effective control strategies. The utilization of modern analytical tools such as GIS (Geographic Information System) is crucial in estimating hotspot areas for targeted control strategies. CONCLUSIONS: Anopheles introlatus has been incriminated as vector of P. knowlesi in Hulu Selangor. The cases of P. knowlesi are on the increase and further research using molecular techniques is needed.

Sequence analysis on the mitochondrial COXI gene of recent clinical isolates of Plasmodium knowlesi in Klang valley, peninsular Malaysia

The cytochrome oxidase subunit I (COXI) gene sequences of three recent (2007- 2008) clinical Plasmodium knowlesi isolates from Klang Valley, peninsular Malaysia, were determined and compared with those of older (1960’s) peninsular Malaysia, recent isolates from Sarawak (on Borneo Island), and an isolate from Thailand. Multiple alignment of the sequences showed that the three clinical isolates were more similar to the older peninsular Malaysia isolates than to those from Sarawak and Thailand. Phylogenetic tree based on the COXI sequences revealed three distinct clusters of P. knowlesi. The first cluster consisted of isolates from peninsular Malaysia, the second consisted of Sarawak isolates and the third composed of the Thailand isolate. The findings of this study highlight the usefulness of mitochondrial COXI gene as a suitable marker for phylogeographic studies of P. knowlesi.