Artemisinin Based Combination Therapies ( Acts )

Quinine alkaloid was used briefly to treat heart problems and cardiac arrhythmia and became a standard for cardiac therapy. This lead to the discovery of a second alkaloid called quinidine that is found in the tree bark. This is primarily used in prescriptions to treat arrhythmia. However, this alkaloid has not yet been able to be synthesized by scientists, requiring the natural bark of the tree for its

Brian, G, Y., Greenwood, D, A., Fidock, Dennis, E, K., Stefan, H, I. Kappe, P., Alonso, L., Frank, H and Collins, P (2008) “Malaria progress and prospects for eradication.” Journal Clinical Investiment. 118: 1266-1276.

- Quinine, which helps cure malaria, is obtained from the bark of the cinchona tree found in South America.

The symbol is a quinine tree. Quinine is an alkaloid found in the bark of the cinchona tree. Quinine has been used to treat malaria,a recurring disease marked by severe chills and fever since the early 1600s. It was the best chemotherapeutic agent available to combat the disease until the 1920s. Malaria treatment by quinine marked the first successful use of a chemical compound to treat an infectious disease. The quinine tree, is the national tree of

There have been many attempts at preventing malaria, none of which have been very successful. These have usually involved protecting human beings from mosquitoes, the dreaded carriers

However, leather corpses are not even worse. When Hydroquinone is used at doses higher than 2% or over a period of longer than three months, the whole skin lightening activity may have some negative, even paradoxical results. Dr. Kassim explains, "With higher levels of the drug, there has been a report of the development of exogenous lubricant infections, darkening of the skin for a long time and very resistant to any treatment. Possible skin reactions may develop with lower doses, the risk will increase with higher

treatment includes non-steroidal anti-inflammatory drugs like ibuprofen and disease modifying anti rheumatic drugs like chloroquine. In this study several dilutions of Ibuprofenand Chloroquine were evaluated for their mutagenicity and cytotoxicity alone and in combination by using Ames Salmonella/microsome assay and MTT [(3-(4, 5 dimethylthiazole –2 yl)-2, 5 diphenyl tetrazolium bromide)] assay using BHK-21 cell lines. Result indicates that Chloroquine and Ibuprofen showed non mutagenic behaviour at lower doses with both strains TA 100 and TA98 but Chloroquine at higher concentration (800ug/ml)showed mutagenic potential with bacterial strain TA100 and a slight mutagenic potential against TA98.Whereas Ibuprofen at higher concentration (10,000ug/ml)showed slight mutagenic potential against TA98. Furthermore, combination Chloroquine-Ibuprofen showed mutagenic potentialat higher concentration (3200-40000µg/ml) with TA98, and a slight mutagenic potential at 1600-20000 and 3200-40000µg/ml with TA100. However,in Cytotoxicity evaluation,chloroquine was cytotoxic at concentrations 200µg / ml, 400 µg / ml, 800µg / ml, 1600µg / ml and 3200µg / ml. On contrast, Ibuprofen at concentrations 10000 µg / ml, 20000 µg / ml and 40000 µg / ml showed cytotoxic effects on BHK-1 cells, In conclusion, the toxicity profiles of both the drugs were shown no mutagenic and cytotoxic potential at

The rational use of click approach for the discovery of new medicinal agents takes advantages of the structurally unique compounds provided by the rapid increase of molecular complexity [1]. Quinazoline compounds tethered to biomolecules via triazole linker produced by combination of an unusual quinazolinone scaffold with the possibility of functionalization at N-atoms were not reported. Quinazoline and its derivatives are versatile nitrogen heterocyclic compounds, which known as a promising class of biologically active compounds. quinazolin-4-one derivatives exhibited a wide range of pharmacological properties such as CNS depressant, sedative, hypnotic, antidepressant, anesthetic, tranquilizer, anticonvulsant, muscle relaxant, antiviral, antibacterial,

The five active compounds were submitted to the evaluation of their in vitro potency against P. falciparum, and the standard drug mefloquine was used as reference parameter, as shown in Table 2. Mefloquine exhibited an IC50 value of 0.04±0.01 μM. In comparison to mefloquine, vanillinyl moiety-bearing derivatives of N-acylhydrazone-1,2,4-oxadiazole SintMed2 (4-mehylsubstituted), SintMed5 (4-bromosubstituted) and SintMed6 (4-nitrosubstituted) displayed potent anti-P. falciparum activities. While compound SintMed5 was found to be almost as potent as mefloquine with IC50 of 0.07±0.12 μM, the other two analogues SintMed2 and SintMed6 were less potent, but still exhibited expressive activities: 0.12±0.16 μM and 0.20±0.16 μM, respectively. Replacement

Fluoroquinolones(FQs) antibiotics were first introduced in the US market in the 1980s.1 Since their introduction, FQs have been used extensively to treat a wide range of infections. 2 Initially, these agents were used to treat infections caused by gram negative bacteria. However, newer agents in this class have gained further coverage of gram positive bacteria, atypical pathogens and even anaerobes. 3 FQs have a distinctive mechanism of action as they are the only class of antimicrobial agents in clinical use that are direct inhibitors of bacterial DNA synthesis. 3

1; see norfloxacin for ring numbering) (867). These newer quinolones differ among themselves principally in the nature of substituents attached to the nitrogen at the 1 position and presence of a carbon or nitrogen at position 8 of the quinolone nucleus. Compounds with a nitrogen in the 8 position are termed 1,8-naphthyridines, but for simplicity will be referred to here as quinolones. (886) fluoroquinolones are potent broad spectrum antibiotic agents. Two classifications have been described: chemical and biological. Quinolones have been classified into 4 groups according to their

According to the Malaria Vaccine Institute, almost 600 million people suffer from malaria each year, and more than one million people die from this disease every year, the most deaths come from children younger than five. Malaria is endemic to over 100 countries in Africa, Asia, Latin America, the Middle East, and the South Pacific, around 40% of the world population. Malaria is caused by a parasite that is transferred by the bite of an infected female Anopheles mosquito. The most deadly form of malaria is known as Plasmodium falciparum because almost all deaths from malaria are caused by this specific one. In addition to being the deadliest form of malaria, Plasmodium falciparum destroys red blood cells along with causing complications with the kidneys, lungs, and brain. In more serious cases, it can cause permanent neurological effects and even death. As the Nobel Assembly said at the announcement of the Nobel Prize in Physiology or Medicine, “Diseases caused by parasites have plagued humankind for a millennium and constitute a major global health problem. In particular, parasitic diseases affect the world’s poorest populations and represent a huge barrier to improving human health and wellbeing”. Youyou Tu, one of the winners of the prize, discovered Artemisinin, a drug that has significantly reduced the mortality rates for patients suffering from malaria by killing the malaria parasites an early stage of their development.

Synthesis of bioactive compounds with therapeutic potential has been a considerable challenge in the recent years.Nitrogen-containing heterocycles; comprising

An urgent health public concern is raised due to the recent emergence of artemisinin resistance in P. falciparum17. Artemisinin-based combination therapy is the front-line antimalarial treatment due to its fast-acting mechanism and high potency against falciparum malaria. Surprisingly, the molecular target of this potent antimalarial drug has recently been identified to be the PI3-kinase of P. falciparum18-20. This finding, along with the essentiality and significance of PI3P described above, accentuates the need to decipher the PI3P-regulated cellular functions in P. falciparum. More importantly, many Plasmodium proteins are unique to the parasite (e.g., apicoplast enzymes and FCP), providing excellent targets for drug development. All in all, a more thorough comprehension of the important PI3P functions on the molecular basis allows for an explicit way to develop preventive and therapeutic interventions against malaria. Identification of PI3P effector proteins from a systemic point of view may provide a combinatorial drug therapy and strategy to bypass or delay the development of drug

Bdq, a diarylquinoline, inhibits of mycobacterial ATP synthase (Andries et al., 2005; Koul et al., 2007). It has inhibitory activity against both active and