DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. The enzyme causes negative supercoiling of the DNA or relaxes positive supercoils. It does so by looping the template so as to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, and ciprofloxacin.
Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partially hydrogenated form of harmine.
Carvacrol, or cymophenol, C6H3(CH3)(OH)C3H7, is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano.
Malaria culture is the method to grow malaria parasites outside the body i.e. in an ex vivo environment. Although attempts for propagation of the parasites outside of humans or animal models reach as far back as 1912, the success of the initial attempts was limited to one or just a few cycles. The first successful continuous culture was established in 1976. Initial hopes that the ex vivo culture would lead quickly to the discovery of a vaccine were premature. However, the development of new drugs was greatly facilitated.
Malaria antigen detection tests are a group of commercially available rapid diagnostic tests of the rapid antigen test type that allow quick diagnosis of malaria by people who are not otherwise skilled in traditional laboratory techniques for diagnosing malaria or in situations where such equipment is not available. There are currently over 20 such tests commercially available. The first malaria antigen suitable as target for such a test was a soluble glycolytic enzyme Glutamate dehydrogenase. None of the rapid tests are currently as sensitive as a thick blood film, nor as cheap. A major drawback in the use of all current dipstick methods is that the result is essentially qualitative. In many endemic areas of tropical Africa, however, the quantitative assessment of parasitaemia is important, as a large percentage of the population will test positive in any qualitative assay.
Alstonia scholaris, commonly called blackboard tree or devil's tree in English, is an evergreen tropical tree in the family Apocynaceae. It is native to southern China, tropical Asia and Australasia, it is a commonly planted ornamental plant in these areas. It is a toxic plant, but traditionally it is used medicinally for myriad diseases and complaints.
Cycloguanil is a dihydrofolate reductase inhibitor, and is a metabolite of the antimalarial drug proguanil; its formation in vivo has been thought to be primarily responsible for the antimalarial activity of proguanil. However, more recent work has indicated that, while proguanil is synergistic with the drug atovaquone, cycloguanil is in fact antagonistic to the effects of atovaquone, suggesting that, unlike cycloguanil, proguanil may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition.
Alternariol is a toxic metabolite of Alternaria fungi. It is an important contaminant in cereals and fruits. Alternariol exhibits antifungal and phytotoxic activity. It is reported to inhibit cholinesterase enzymes. It is also a mycoestrogen.
Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.
Clinafloxacin is an investigational fluoroquinolone antibiotic. Despite its promising antibiotic activity, the clinical development of clinafloxacin has been hampered by its risk for inducing serious side effects.
Evoxine (haploperine) is a furoquinoline alkaloid with hypnotic and sedative effects. It is found naturally in a variety of Australian and African plants including Evodia xanthoxyloides and Teclea gerrardii.
Warburgia ugandensis, also known as Ugandan greenheart, is a species of evergreen tree native to Africa. Countries in which the plant species is found include Kenya, Tanzania and Uganda. The wood is resistant to insect attack and very strong. It was commonly used for the yoke pole of ox-wagons, the Disselboom. Early Indian immigrants to Kenya, working on the construction of the railway, used the leaves to flavor their curries before the chilli plant was commonly introduced. The flavor is fiercely hot and subtly different from chillies.
Ziziphus oenoplia, commonly known as the jackal jujube, small-fruited jujube or wild jujube, known as मकोरा Makora in Hindi and as तोरण वेल in [[[Marathi]], is a flowering plant with a broad distribution through tropical and subtropical Asia and Australasia.
Panicudine (6-hydroxy-11-deoxy-13-dehydrohetisane) is a C20-diterpene alkaloid of the hetisine type, first isolated from Aconitum paniculatum. It has empirical formula C20H25NO3 and a melting point of 249–250 °C. The structure was determined to be a hetisine type diterpene by noting infrared spectrum absorption bands of 3405 cm−1 (OH), 1718 (C=O), and 1650 (C=C), a proton magnetic resonance spectrum with "secondary hydroxy (4.02 ppm, m, 1H, W1/2 = 10 Hz), exomethylene (4.87 and 4.76 ppm, br.s, 1H each), and tertiary methyl (1.29 ppm, s, 3H) groups and the absence of N-methyl, N-ethyl, and methoxy groups." Additional ultraviolet spectrum and carbon-13 NMR data, confirmed by high resolution mass spectrometry, completed the determination of the structure.
Corydaline is an acetylcholinesterase inhibitor isolated from Corydalis yanhusuo.
Sarcococca saligna, the sweet box or Christmas box, is a species of flowering plant in the family Buxaceae. This shrub is native to northern Pakistan. Its common name in Pakistan is sheha.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of proteins present on the membrane surface of red blood cells that are infected by the malarial parasite Plasmodium falciparum. PfEMP1 is synthesized during the parasite's blood stage inside the RBC, during which the clinical symptoms of falciparum malaria are manifested. Acting as both an antigen and adhesion protein, it is thought to play a key role in the high level of virulence associated with P. falciparum. It was discovered in 1984 when it was reported that infected RBCs had unusually large-sized cell membrane proteins, and these proteins had antibody-binding (antigenic) properties. An elusive protein, its chemical structure and molecular properties were revealed only after a decade, in 1995. It is now established that there is not one but a large family of PfEMP1 proteins, genetically regulated (encoded) by a group of about 60 genes called var. Each P. falciparum is able to switch on and off specific var genes to produce a functionally different protein, thereby evading the host's immune system. RBCs carrying PfEMP1 on their surface stick to endothelial cells, which facilitates further binding with uninfected RBCs, ultimately helping the parasite to both spread to other RBCs as well as bringing about the fatal symptoms of P. falciparum malaria.
Skimmianine is a furoquinoline alkaloid found in Skimmia japonica, a flowering plant in family Rutaceae that is native to Japan and China. It is also a strong acetylcholinesterase (AChE) inhibitor.
Lichexanthone is an organic compound in the structural class of chemicals known as xanthones. Lichexanthone was first isolated and identified by Japanese chemists from a species of leafy lichen in the 1940s. The compound is known to occur in many lichens, and it is important in the taxonomy of species in several genera, such as Pertusaria and Pyxine. More than a dozen lichen species have a variation of the word lichexanthone incorporated as part of their binomial name. The presence of lichexanthone in lichens causes them to fluoresce a greenish-yellow colour under long-wavelength UV light; this feature is used to help identify some species. Lichexanthone is also found in several plants, and some species of fungi that do not form lichens.
David A. Fidock, is the CS Hamish Young Professor of Microbiology and Immunology and Professor of Medical Sciences at Columbia University Irving Medical Center in Manhattan.
