A number of mono and bicyclic nitroimidazoles were screened for in vitro antileishmanial activity. Among these, compounds belonging to the class of nitroimidazo[2,1-b]oxazoles showed moderate to good activity. This class of compounds had been reported previously to have pronounced antitubercular activity, particularly CGI17341 (5a). In the present study (5a) and (5d) and (7) were found to be more potent antileishmanials in vitro than the standard and less toxic in relation to a reference compound. (7) Was earlier formulated to have the phenyl group located on C-2(5b) [5].
Key words: Nitroimidazoles, antileishmanial activity, nitroimidazooxazoles, satranidazole
Nitroimidazoles, known to have a wide antimicrobial spectrum, are particularly potent against amoeba, giardia and trichomonas[1,2]. Our earlier extensive foray into the medicinal chemistry of nitroimidazoles resulted in the development of satranidazole(satrogylR), a potent antiamoebic and antitrichomonal drug with clear superiority over the standard drug metronidazole (3a)[3]. (1a) and its congeners had also potent antianaerobic activity superior to that of (3a) [4]. A further outcome of our research was the discovery of significant antitubercular activity in a series of 2,3-dihydro-6-nitroimidazo[2,1-b]oxazoles among which CGI17341 (5a) was the most potent[5,6] which inspired the development of two molecules which are in clinical trials now, nitroimidazooxazole OPC67683, delamanid[7,8] and nitroimidazooxazine, PA824[9,10].
Leishmaniasis is a worldwide disease caused by protozoan parasites of the genus of leishmania which cause a range of diseases in humans ranging from disfiguring cutaneous lesions (CL) to visceral leishmaniasis (VL)[11]. Despite the widespread occurren...
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...sine. Five compounds having the nitroimidazooxazole scaffold had appreciable activity but among these (5c) and (5e) were less active than the standard. Compound (5a) with an ethyl group and (5d) with a CCl3 group were about 3.5 times more potent than standard while (7) with a phenyl group at C-3 was twice as active. In the macrophage assay, (5a) had 20 times the potency of the standard, (5d) about 3.5 times and (7) about 2 times. (5a) and (7) were not cytotoxic below 90µg/ml compared to a figure of 0.009 for podophyllotoxin while the IC50 of (5d) in this test was 73.3. These three nitroimidaoxazoles have been taken up for in vivo and genotoxicity studies. The results will be published elsewhere.
The present study reveals that 2,3-dihydro-6-nitroimidazo[2,1-b]oxazoles like the antitubercular CGI 17341( 5a) represent important novel leads for antileishmanial activity.
On the second day of class, the Professor Judit Kerekes developed a short chart of the Xmania system and briefly explained how students would experience a number problem. Professor Kerekes invented letters to name the quantities such as “A” for one box, “B” for two boxes. “C” is for three boxes, “D” is for four boxes and “E” is for five boxes. This chart confused me because I wasn’t too familiar with this system. One thing that generated a lot of excitement for me was when she used huge foam blocks shaped as dice. A student threw two blocks across the room and identified the symbol “0”, “A”, “B”, “C”, “D”, and “E.” To everyone’s amazement, we had fun practicing the Xmania system and learned as each table took turns trying to work out problems.
Discussion and Conclusions: Interpreting these results have concluded that relative reactivity of these three anilines in order of most reactive to least reactive go; Aniline > Anisole > Acetanilide. Aniline, has an NH2 , the most active substituent , and adds to any ortho/para position available on the ring. This data is confirmed with the product obtained, (2,4,6 tribromoaniline, mp of 108-110 C). As for anisole, it has a strongly activating group attached, OMe an alkoxy group, and it added in two of the three available spots, both ortho. The results conclude: (2,4-Dibromoanisol mp 55-58 C ). Acetanilide has a strong activating group attached, acylamino group, but this group is large and the ortho positions are somewhat hindered so the majority of the product obtained added at the para position, results conclude: (p-bromoacetanilide mp 160-165 C). Since all the substituents attached to the aromatic rings were activators the only products able to be obtained were ortho/para products.
Pharmaceuticals have examined and found to ”work by changing the biological functions of the target cells in the body through chemical agents“ (Doweiko, 2015, p. 16). ”Many people in the past have thought that drugs that
Compounds resulting from heterocyclic chemistry form a huge family of variations of organic compounds with cyclic or acyclic structures having carbons and at least another element with the most common being sulfur, oxygen, fluorine or nitrogen 49. Such heterocyclic compounds must have their rings having heteroatoms and the rings could be unsaturated or saturated as well 1. These compounds are usually classified as aromatic or alicyclic heterocycles 6. The latter contain cyclic analogues of thioethers, ethers and amines 6. It has been studied before that the families of nitrogen- sulfur heterocycles have aromatic compounds that are very stable19. Also, fluorinated compound using trifluoromethyl group is often used to reduce in vivo metabolism of potential drugs, in addition to improving cellular membrane permeability (LogP)88. Sulfur and Nitrogen organic compounds heterocycles are basically drawn from aromatic heterocycles realized when a heteroatom occupies the position of a carbon atom in the ring of an organic aromatic
accomplished the synthesis of non-toxic aminoalkyl substituted isonicotinyl hydrazide by Mannich reaction.[148][ref:] The Mannich products were found to be more active against several Gram-positive and Gram-negative bacteria. Karthikeyan et al. reported the synthesis and biological activity of 2,4-dichloro-5- fluorophenyl substituted Mannich base derivatives 27 (figure 8 ).[149][ref:] TheMannich base derivatives showed good antibacterial and antifungal
Plenty of fungal problems exist, including athlete’s foot, jock itch, ringworm, and onychomycosis (fungal infection beneath nails). However, many antifungal drugs exist as well, such as Lamisil, which is the most effective. Using the molecule terbinafine hydrochloride, it puts holes in the cell membranes of fungal cells, and can destroy fungi. Despite this, Lamisil has many problems such as harmful side effects, and a high cost, and can therefore be vastly improved. Some of Lamisil’s competitors, such as Tinactin, offer a similar medication for a cheaper price, and other analogs of the drug could prove to be safer and even more effective. For now though, Lamisil, the 87th best selling prescription drug in the world, is the best antifungal medication1.
Treponema pallidum is a Gram-negative bacterium that has a spiral shape (1). They are about 6 to 20um in length and 18-20um in diameter (1). Treponema pallidum can only survive within a host which makes them obligate internal parasites, meaning that outside a host this organism will die due to the absence of nutrients, exposure to oxygen and heat. Also since this organism can’t be grown on a culture medium, animal models are used to study T. pallidum (1). Treponema pallidum bacteria consist of an inner and outer membrane with a thin peptidoglycan cell wall lacking liposaccharides (1). They have a distinctive corkscrew motility with the aid of 6 endoflagellas (2). The specific classifications of Treponema pallidum are the following: Scientific name- Treponema pallidum, Common name- Syphilis. Treponema causes syphilis, yaws, and spinta. Borrelia causes Lyme disease and relapsing fever and Leptospira causing leptospirosis (5). What makes this microorganism special to the human population is that it causes infection to its host by entering the body through microscopic skin or mucous abrasions via direct personal contact with the lesions (sexual or kissing), blood transfusions, accidental bacterial inoculation, and transplacental passage (2). According to the CDC website there are 55,400 people diagnosed with Syphilis every year and 322 reported cases of congenital Syphilis in 2012 (6).
Schulman, Joshua M., and David E. Fisher. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Aug. 0005. Web. 24 Apr. 2014.
This parasite is spread through the bite of sandflies. There are three different types of infections and they each show varying degrees of severity. The cutaneous form produces mild skin ulcers, mucocutaneous produces ulcers in the mouth and nose, and the visceral form of the disease starts with skin ulcers and then fever, low red blood cell count, and an enlarged spleen and liver. The parasite is detected by a microscope and visceral can also be found by doing blood tests. 12 million people are in infected in 98 different countries and 2 million new cases are found every year. The disease also kills around 20 to 50 thousand people a year.
Victora , C. , Aquino, E. Carmo Leal, M. Augusto Monteiro, C., Barros F.C & Szwarcwald, C. (2011) The Lancet 377, (97800), Pages 1863-1876. doi: 10.1016/S0140-6736(11)60138-4
Amphotericin B is a polyene antifungal agent that targets the cell membrane of a fungal cell. The cell membrane has a lipid bilayer component consisting of sterols. One of the sterols in this layer is ergo sterol. Ergo sterol provides stability and flexibility to the cell membrane. Amphotericin B penetrates the cell wall and inserts itself into the cell membrane. Once Amphotericin B enters the cell membrane it serves as an aggregate binding close to ergo sterol. This binding of ergo sterol and amphotericin B creates pores in the intracellular membrane causing the loss of potassium and ultimately the organism will die. This drug has not been proven effective in treating PAM, yet all known cases surviving this infection have been treated with Amphotericin B. Work is currently being done to determine what specific to Naegleria Fowleri makes it pathogenic and if these virulence factors can be specifically targeted by drugs. In 2014 the U.S. Food and Drug administration approved a drug called Miltefosine in treatment of Naegleria Fowleri. Miltefosine was originally intended as an anti-cancer treatment. Studies are still unclear as to whether or not Miltefosine will be effective in fighting the organism because this drug is still so new on the market. Test methods for detecting this organism are fairly limited because there are only a hand full of laboratories
Since antibiotics, such as penicillin, became widely available in the 1940s, they have been called miracle drugs. They have been able to eliminate bacteria without significantly harming the other cells of the host. Now with each passing year, bacteria that are immune to antibiotics have become more and more common. This turn of events presents us with an alarming problem. Strains of bacteria that are resistant to all prescribed antibiotics are beginning to appear. As a result, diseases such as tuberculosis and penicillin-resistant gonorrhea are reemerging on a worldwide scale (1).
...es, such as UroShield, which has been observed as promoting neutrophil killing of planktonic and biofilm Streptococcus epidermidis cells (Loike et al., 2013).
Product 3 was isolated in a low yield of 27% and with some solvent impurities as shown by the analytical techniques but it was indeed synthesised successfully.
Pyrrole has been a molecule of great interest due to its heterocyclic aromatic properties. The lone pair on the nitrogen is delocalised within the ring, causing the heterocycle to be electron-rich . This causes the ring to become increasingly nucleophilic, and therefore makes it susceptible to attack from electrophiles . The addition of these new substitutions makes more important molecules , which have a huge contribution to not only the chemical industry, but also the biological. 1 Substituted pyrrole molecules are fantastic precursors to make complex molecules, such as medicines, agrochemicals and dyes. Indole, an important benzo-pyrrole, is the basis of the important protein, tryptophan and has functions as a neurotransmitter in the brain. The neurotransmitter, serotonin, is important in making modern drugs such as sumatriptan which treats migraines.2