Malaria.


 * __ Disease/Drug of interest: Malaria __**

Mosquitoes have become notorious for being the number one transmitter of disease across the world. Their ability to extract a disease from an individual’s blood, and then transfer that disease to the next individual it infects has proven to be extremely deadly. Female Anopheles mosquitoes in particular can carry a variety of diseases, with the most prominent being malaria [2]. Nearly half of the world’s population is at risk of being infected with malaria, and death tolls are at a staggering half a million each year [4]. Transmission occurs when a female bites a human, and extracts the parasite from the human blood. This blood is then used to nurture the female’s eggs. Thus, once the female gives birth to these eggs, the offspring are also carriers of the disease. Seeing as one female can lay 100 to 200 eggs, malaria can spread very quickly and on a very large scale [3]. The parasite being transmitted is Plasmodium, and contains four different species. These species include: P. vivax, P. ovale, P malariae, and P. falciparum. P. falciparum is the deadliest species, and is the one most commonly targeted by antimalarial drugs. This parasite is vicious, and develops in the liver, where it causes red blood cells to burst. The bursting of the red blood cells can cause anemia, while also releasing toxic waste into the blood stream [4]. Due to malaria’s ability to spread and kill quickly on a large scale, it is imperative that high risk regions such as Sub-Saharan African be supplied with the knowledge, equipment, and medication needed for prevention. With proper funding, people in these regions can be educated about the fact that early detection is key, and that pregnant women and children are most at risk. Furthermore, proper funding will allow for the delivery and implementation of preventative equipment such as mosquito nets [1]. Finally, research on antimalarial drugs, such as Malarone can be increased. These drugs can then be delivered and implemented in high risk regions around the world.
 * Motivation and Background: **
 * Figure 1: ** This is an image of an Anopheles mosquito [2]. Female anopheles mosquitos are the only type of mosquito capable of carrying malaria. They acquire the parasite when they bite a host and pick up the disease from them. The parasite is then transmitted to next host who is bit.

**References/External Links:** [1] 10 facts on malaria http://www.who.int/features/factfiles/malaria/en/ [2] Anopheles Mosquitoes https://www.cdc.gov/malaria/about/biology/mosquitoes [3] Do all mosquitoes transmit malaria? http://www.who.int/features/qa/10/en/ [4] Malaria https://www.cdc.gov/malaria/

The target for a variety of antimalarial drugs is Dyhydrofolate reductase. This is an enzyme that is responsible for the replication, division, and reproduction of the plasmodium parasite. When deactivated, the parasite is unable to produce the pyrimidine thymine, and thus the DNA cannot base pair. This halts reproduction of the parasite.
 * __ Target Information: __**
 * Figure 2: ** This image depicts the Dyhydrofolate reductase enzyme. This protein is responsible for the production of thymine bases, and plays a large role in DNA base pairing as well as reproduction.

Approximately 20kDa
 * Size: **

DFHR is found throughout the body, and is always expressed.
 * Location: **

DFHR plays a key role in DNA base pairing as it is responsible for the production of the pyrimidine base thymine
 * Function in a normal cell: **

Malaria is not a new disease by any means, and thus drugs to prevent and cure it have been developed for quite some time. In turn, malaria has evolved over the years and has developed numerous resistances. Because of this, drugs are often administered in conjunction with one another. As is the case with the drug studied here, Malarone. Malarone is an antimalarial that consists of both proguanil and atovaquone. Malarone targets DHFR by inhibiting its production. By competitively inhibiting this enzyme, the parasite cannot reproduce and spread.
 * __ Drug Information: __**

**Schematic figure of drug**:


 * Figure 3: ** This image depicts the schematic of Proguanil. The linear structure allows it to more easily bind to the DFHR enzyme found in the malarial parasite.
 * Figure 4: ** This image depicts the schematic of Atovaquone. This structure is slightly more bent than proguanil, and a greater number of ring structures can be clearly identified.

**Formula**: __Proguanil__: C11 H16 Cl N5 __ Atovaquone __ : C22 H19 Cl O3

**Molecular weight**: __ Progaunil __ : 253.73 g/mol __ Atovaquone __ : 366.84 g/mol

**CAS Number**: __ Progaunil __ : 500-92-5 __ Atovaquone __ : 95233-18-4

**Delivery method**: Malarone is administered orally.

Upset stomach, mild diarrhea, constipation, sore mouth
 * Side effects ** :

Biguanide, Imidodicarbonimidic diamide
 * Other names ** :

**Maker or company**: GlaxoSmithKline

**Is it patented**? Malarone is no longer patented as it expired in 2013.

**Clinical Trials Info**: A total of 23 clinical trials were conducted.

**__Origin__**__:__ Malarone appears to be synthetic, as no known origins could be found

**Alternatives to this drug**: A variety of antimalarial drugs are available, and all serve as potential alternatives to Malarone. Some of these alternatives include: quinine, chloroquine, amodiaquine, pyrimethamine, mefloquine, clindamycin, doxycycline.

**Other uses**: can this drug be used to treat other diseases/conditions? Malarone is used to treat malaria exclusively. The combination of proguanil and atovaquone work specifically against Plasmodium.