Metronidazole was synthesized by France's Rhone-Poulenc laboratories and introduced in the mid-1950s under the brand name Flagel in the US, while Sanofi-Aventis markets metronidazole globally under the same trade name, Flagyl, and also by various generic manufacturers. Metronidazole is one of the rare examples of a drug developed as ant parasitic, which has since gained broad use as an antibacterial agent. Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Metronidazole is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms: Trichomoniasis: symptomatic, asymptomatic, asymptomatic consorts; Amebiasis: acute intestinal amebiasis (amebic dysentery) and amebic liver abscess; Anaerobic bacterial infections; Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess; Skin and skin structure infections; Gynecologic infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection; Bacterial septicemia; Bone and joint infections, as adjunctive therapy; Central Nervous System infections, including meningitis and brain abscess; Lower Respiratory Tract infections, including pneumonia, empyema, and lung abscess; Endocarditis. Metronidazole is NOT effective for infections caused by aerobic bacteria that can survive in the presence of oxygen. Metronidazole is only effective against anaerobic bacterial infections because the presence of oxygen will inhibit the nitrogen-reduction process that is crucial to the drug's mechanism of action. Once metronidazole enters the organism by passive diffusion and activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced; this process includes intracellular electron transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and formation of a short-lived nitroso free radical. Because of this alteration of the metronidazole molecule, a concentration gradient is created and maintained which promotes the drug’s intracellular transport. The reduced form of metronidazole and free radicals can interact with DNA leading to inhibition of DNA synthesis and DNA degradation leading to death of the bacteria. The precise mechanism of action of metronidazole is unknown. Metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment.

Hydroxychloroquine possesses antimalarial properties and also exerts a beneficial effect in lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis. Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown. Hydroxychloroquine is used for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis.

Pyrimethamine, sold under the trade name Daraprim, is one of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. In addition it was approved in Chemoprophylaxis of Malaria. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Primaquine is a oral medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. Primaquine is an alternative treatment for Pneumocystis pneumonia together with clindamycin. Primaquine is lethal to P. vivax and P. ovale in the liver stage, and also to P. vivax in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood. Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity. In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein orosomucoid. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Common side effects of primaquine administration include nausea, vomiting, and stomach cramps. Primaquine phosphate is recommended only for the radical cure of vivax malaria, the prevention of relapse in vivax malaria, or following the termination of chloroquine phosphate suppressive therapy in an area where vivax malaria is endemic. Patients suffering from an attack of vivax malaria or having parasitized red blood cells should receive a course of chloroquine phosphate, which quickly destroys the erythrocytic parasites and terminates the paroxysm. Primaquine phosphate should be administered concurrently in order to eradicate the exoerythrocytic parasites in a dosage of 1 tablet (equivalent to 15 mg base) daily for 14 days.

Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. Proguanil in combination with atovaquone are marked under the brand name malarone, which is indicated for the treatment of acute, uncomplicated P. falciparum malaria and for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. Atovaquone and proguanil, interfere with 2 different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis. Recently were done experiments, which confirmed the hypothesis that proguanil might act on another target than dihydrofolate reductase. In addition, was made conclusion, that effectiveness of malarone was due to the synergism between atovaquone and proguanil and may not require the presence of cycloguanil.

Quinine soluble salts possess the extremely bitter taste, that may have a perplexing problem especially to children. That is why the most common combinations which are administered in this way are the sulphate, salicylate, tannate and certain esters. Quinine tannate, an insoluble quinine salt has been known in medicine for a very long time. However, many experiments have revealed that quinine tannate was practically inert as a medicinal substance.

Clioquinol is a broad-spectrum antibacterial with antifungal properties, bacteriostatic. It is used as an antifungal and antiprotozoal topical drug OTC product for treatment of human infections. Previousely was used for wide number of intestinal disorders including lambliasis, shigellosis, balantidiral dysentery and some forms of diarrheas. The physiologic effect of clioquinol is by increased histamine release and cell-mediated immunity. It is a member of a family hydroxyquinolines which inhibit certain enzymes related to DNA replication. It is a copper, iron and zink chelating agent. It is an organic molecule with a quinolinic acid as its apparent core which itself is a neurotransmitter. In large doses it possesses neurotoxicity and may induce neurological disease such as subacute myelo-optic neuropathy by creating copper deficiency that leads to zink excess. SMON (Sub-Acute-Myelo-Optical-Neuropathy) - a polio-like disease began as an epidemic in 1959 in Japan was believed to be a Clioquinol caused. Clioquinol is a standardized chemical allergen. It has been resurrected as a potential treatment for Alzheimer's disease since it perturbs metallo-chemistry of amyloid and clioquinol treatment has been shown to be beneficial in a mouse model of Alzheimer's disease.

Chlorquinaldol is a halogenated hydroxyquinoline with properties similar to those of clioquinol. It is mainly applied topically in infected skin conditions and in vaginal infections. The product is applied for local treatment of cortico-sensitive dermatosis with moderately manifested superinfection, acute and subacute eczema, dermatitis, pyodermia, intertrigo, infected wounds, dermatomycosis, pemphigus in newborn. Chlorquinaldol is also used as antiseptic, fungistat, or deodorant. Chlorquinaldol is not commercially available in the U.S. but is used in other countries principally as an amebicide for nonspecific diarrheas and gynecologic infections. It is known most commonly under the proprietary name of Sterosan. Other trade names include Cynotherax, Gyno-Sterosan, Saprosan, Siogeno, Siosteran, Slosteran and Steroxin.

Trimetrexate, a second-generation folate antagonist which was used under brand name NEUTREXIN with concurrent leucovorin administration (leucovorin protection) was indicated as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Nevertheless, this product was discontinued. In present time, trimetrexate with a different combinations is in the phase II of clinical trial for the treatment the following cancer diseases: pancreatic cancer and colorectal cancer (in combination with fluorouracil and leucovorin) and to treat a refractory acute leukemia in combination with leucovorin. Trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of purine biosynthesis. The result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.

Halofantrine is a blood schizonticidal antimalarial agent with no apparent action on the sporozoite, gametocyte or hepatic stages of the infection. It is used only to treat but not to prevent malaria. Has been marketed by GlaxoSmithKline as HALFAN (halofantrine hydrochloride) in 250 mg tablets indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax. Among side effects is cardiac arrhythmia. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It was reported that halofantrine binds to hematin in vitro (crystal structure of the complex) and to to plasmpesin, a haemoglobin degrading enzyme unique to the malarial parasites.