Synthesis, characterization and in vitro antiplasmodial evaluation of 4-& 8-aminoquinoline based-hybrid compounds

Malaria is a deadly disease and its drug resistance has been reported to be a challenge globally. The death toll caused by malaria has increased rapidly in different regions of the world. Quinoline scaffold molecules are combined with other classes of antimalarials to tackle drug resistance. The combination of quinoline scaffolds with other antimalarial compounds and metals-based drugs have been reported to be a potential approach to overcome drug resistance common in the currently used antimalarials. 4-Aminoquinoline was hybridized with selected organic molecules and metal-based compounds to form a class of hybrid compounds containing either an amide bond or ester bond as a linker between the parent molecules. 4-Aminoquinoline derivatives are known compounds and they were prepared via known synthetic routes and characterized. The hybrid compounds were characterized and the FTIR results confirmed the successful linkage of 4-aminoquinoline derivatives to selected organic scaffolds to form hybrid compounds. NMR results confirmed the successful formation of hybrid compounds. MS showed signals of the hybrid molecules confirming the successful isolation of the hybrid compounds. In vitro antiplasmodial assay was performed against asexual parasite and chloroquine was used as a reference drug. The percentage inhibition effects of the hybrid compounds were in a range of 96-102% at 5 µM and 36-96% at 1 µM suggesting that the percentage inhibition effect of the hybrid compounds was influenced by the drug concentration. Hybridization of either 4-aminosalicylic scaffold or ferrocene butanoic acid with 4- aminoquinoline derivatives is a potential synthetic route that can result in potent antimalarials. However, more research is needed to fully understand the structure-activity relationship of these hybrid compounds

Genetic detection of some tick-borne bacterial and protozoan pathogens in ticks collected in Raymond Mhlaba local municipality, Eastern Cape Province, South Africa

Ticks and tick-borne diseases are becoming a major life threatening concern to wildlife, domesticated animals and human health. Besides causing skin damage, ticks infestations have become a growing burden in food security, economic losses and transmitting multides of pathogens. Little data and knowledge is available regarding the occurrence of etiologic agents of tick-borne diseases in the Eastern Cape of South Africa, hence the study was conducted and aimed at screening for genetic material of Anaplasma, Rickettisia, Ehrlichia, Borrelia, Babesia and Theileria species in ticks collected in Raymond Mhlaba District at Eastern Cape, South Africa. Ticks were collected from domesticated animals in Raymond Mhlaba Municipality, and were morphologically identified and processed for DNA extraction. Ticks were chopped into bits and DNA was extracted from the samples with commercial DNA extraction kit. The extracted DNA samples was used to molecularly identify the tick as well as assess the presence of tickborne pathogens belonging to Rickettsia, Babesia, Borrelia, Anaplasma and Erhlichia, and Theileria spp. by PCR using specific primer pairs published in literature. Positive amplicons were sequenced in a commercial sequencing facility. The obtained chromatograms were edited with Geneious bioinformatics software and were subjected to BLASTn and phylogenetic analyses using MEGA7 version for evolutionary relationships with curated reference sequences in GenBank. Nine hundred and sixty two tick samples were collected from domestic animals. Collected tick samples belonged to three genera, which were the Amblyomma, Rhipicephalus and Haemophalis in decreasing order of their abundance. Screening of tick DNA samples by PCR did not show presence of Babesia, Borrelia, Anaplasma and Erhlichia. 13 Positive PCR products were observed for Rickettsia and Theileria spp.. The positive amplicons were purified, sequenced and analysed for speciation of Theileria and Rickettsia. The presence of Rickettsia was detected in 60/994 (6%) from the three genera of ticks. Phylogenetic analyses shows that the sequences obtained are phylogenetically related to members of Spotted fever group Rickettsiae. Genetic material of Theileria spp. was detected from 10/994 ticks with an overall infection of 1% obtained in Rhipicephalus genera. Analyses shows that the sequences obtained are phylogenetically related to T. orientalis complex. The finding from this study therefore expands the knowledge on recent emergence of Theileria and Rickettsia spp. in Raymond Mhlaba Municipality in Eastern Cape, South Afric

Development and in vitro biological studies of polymer-based wound dressings with a high haemostatic ability for the management of wounds

Wounds are usually accompanied by complications such as excessive bleeding and bacteria invasion. The design of wound dressings that rapidly stop excessive bleeding and inhibit bacterial invasion is crucial to promoting accelerated wound healing. To meet the abovementioned requirements in wound dressings, topical gels were prepared from sodium alginate SA and carboxymethylcellulose CMC. The wound dressings were loaded with an antifibrinolytic agent, tranexamic acid TA, essential oils, and a variety of metal-based nanoparticles, and carbon-based biomaterials. The scanning electron microscopy SEM and X-ray diffraction XRD confirmed the successful formation of the nanoparticles. The prepared formulations exhibited in vitro drug release kinetics that best fitted with the Korsmeyer-Peppas model. These gels exhibited good spreadability and viscosity, showing a shear-thinning behaviour with pH between 6.7 and 7.3, signifying suitability for skin application and ease of application. The prepared topical gels exhibited significant antibacterial effects against gram-negative and gram-positive strains of bacteria. SA EO-based formulations showed high antibacterial activity across all bacterial strains, followed by SA-based formulations compared to CMC-based formulations, which exhibited moderate antibacterial activity. Moreover, the prepared gels showed good cytocompatibility, promoted cell proliferation, and exhibited 80 percent wound closure on day 3 compared to the untreated group, which showed a 38 percent wound reduction in vitro. Excellent blood clotting properties were observed with CMC-based gels compared to other formulations. However, all the prepared formulations exhibited outstanding blood clotting ability compared to the control, showing that they can promote rapid blood coagulation. The features presented by the prepared gels reveal that they are suitable for rapid wound healingThesis (PhD) -- Faculty of Science and Agriculture, 202

Unravelling the mechanism of cobalt-catalysed remote C-H nitration of 8-aminoquinolinamides and expansion of substrate scope towards 1-naphthylpicolinamide

Previously, an unexpected Co-catalysed remote C-H nitration of 8-aminoquinolinamide compounds was developed. This report provided a novel reactivity for Co and was assumed to proceed through the mechanistic pathway already known for analogous Cu-catalysed remote couplings of the same substrates. In order to shed light into this intriguing, and previously unobserved reactivity for Co, a thorough computational study has now been performed, which has allowed for a full understanding of the operative mechanism. This study demonstrates that the Co-catalysed remote coupling does not occur through the previously proposed Single Electron Transfer (SET) mechanism, but actually operates through a High-Spin Induced Remote Radical Coupling mechanism, through a key intermediate with significant proportion of spin density at the 5- and 7-positions of the aminoquinoline ring. Additionally, new experimental data provides expansion of the synthetic utility of the original nitration procedure towards 1-naphthylpicolinamide which unexpectedly appears to operate via a subtly different mechanism despite having a similar chelate environment

Quinoline-Based Hybrid Compounds with Antimalarial Activity

The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by drug-drug interactions. In order to overcome the aforementioned factors, several researchers have reported hybrid compounds prepared by reacting quinoline-based compounds with other compounds via selected functionalities. This review will focus on the currently reported quinoline-based hybrid compounds and their preclinical studies