ISONIAZID Isoniazid was identified by pursuing derivatives of nicotinamide. Optimization of nicotinamide produces two distinct drugs with very different charactetistics, rifampin and pyrazinamide. There are two independent tracks of SARs for this drug series, one governing the activation of the prodrug and another governing the interaction of the active species with InhA. Many groups at the 4-position can be activated inside M.tubeculosis, and are possible prodrug structures. After activation, the structural requirments for InhA binding appear to be very stringent. Only the isonicotinoyl core structure is substantially active among many aryl and heteroaryl groups explored. The isonicotinoyl group could be substituted with lower alkyl groups while …show more content…
[47] Chemical modifications of the natural products have produced several clinically important semisynthetic rifamycins with improved pharmacological profiles. SARs are highlighted in the figure below. Pyrazinamide is one of the analog of nicotinamides and shares the same root with isoniazid. It can be only activated under acidic condition. There are two ways of the SAR tracks, which are the activation of the pyrazinamidase (PZase) and also the target interaction of the resulting acid. [46] In the study of Structure-activity relationship, the R1 groups contribute to two important functions: i. The activated species of pyrazinamide, pyrazinoic acid is usually in its anionic form at physiological pH. Thus, it is not permeable or bioavailable. With R1 group, it can masks the acid group and makes the drug permeable to cell membranes. [46] ii. The killing effect of pyrazinoic acid is unlikely a selective process. The presence of R1 group will cause the selective removal of R1 group by M.tuberculosis and other bacteria. Hence, this will lead to desired selectivity of the drug.
These drugs were utilized in order to demonstrate the positive and negative effects on cell communication. Cell communication consists of three steps: reception, transduction, and response. Reception involves the binding of a ligand and a receptor; transduction is a “cascade” of actions between molecules and their proteins, and response is the change that occurs afterwards (1).
Iodination of Salicylamide Purpose The purpose of this experiment is to study the directing effects of substituents on an aromatic ring. Aromatic rings do not undergo electrophilic addition reactions instead they undergo electrophilic aromatic substitution. The study will be made from the reaction of the electrophile, iodide ion with sodium hypochlorite, with salicylamide that has a hydroxyl group (ortho-/para- directing) that is highly activated, electron donating, and an amide group (meta- directing) that is deactivating, electron withdrawing.
The Anasazi or the ancient ones were a very interesting and unknown culture to many people. The Anasazi were the very the beginning. The beginning of what you may ask. The Anasazi were the beginning of a whole culture that still lives on today.The Anasazi culture was an advanced culture . The Anasazi also had an incredible in structures and area the Anasazi lived in. The Anasazi lifestyles was very different then you would think. Were the Anasazi polytheism or monotheism is a good question to ask? We answer that question. What did The Anasazi eat and how did The Anasazi store their food and supplies. The main question is who were The Anasazi. These are the the topic that will be in these paragraphs.
Although some agar plates were hard to see if the streptomycin had a definitive zone of inhibition. Ampicillin, erythro-mycin, penicillin, sulphafurazole was ineffective with no inhibition zone.
speak with a certain eloquence. They tell of a people adept at building, artistic, in
Microbiologist Selman Waksman found this non-toxic compound in 1943 derived from streptomycetes greiseus mold in the soil. It challenged penicillin as the number one antibiotic because it treated several diseases that were untouched by any other drug, specifically tuberculosis. It also treated diseases such as typhoid fever and bubonic plague. Dr. Hinshaw told The New York Times just after the war that Streptomycin has “very great value in some of the most fulminating types of lung tuberculosis” and was especially helpful in combination with some forms of surgical treatment. A few forms of tuberculosis that yielded to Streptomycin were miliary tuberculosis which spread through the bloodstream, tuberculosis meningitis which attacked the spine and brain, tuberculosis of the larynx and vocal cords, and multiple types of tuberculosis of the intestines. Streptomycin is remembered as the first drug to treat untouched diseases during World War II and curing patients of devastating
It is thought to exert its antimicrobial effect by inhibition of protein synthesis. It prevents the binding of amino-acyl-tRNA to the messenger RNA-30S ribosomal subunit.11
To confirm the exact potential mechanism involved in the uptake of Azide – 1, a competitive inhibition was carried out in glutamine dependent cancer cell lines: HT1080 – luc2, U87MG – luc2 and HepG2 – luc2 using the specific inhibitor GPNA for the system ASCT2. The reason for choosing to test the involvement of this specific type of transporter in the uptake of Azide – 1 is because the signal produced by Azide – 1 in HT1080 – luc2 and HepG2 – luc2 cells could be reduced in the antagonistic effect assay by using L – glutamine which is the natural competitor for binding to glutamine transporter systems ASC and N. It was also figured out in this study that HepG2 – luc2, HT1080 – luc2 and U87MG – luc2 express the ASCT2 transporter on the cell surface. GPNA decreased the signal intensity in HT1080 – luc2 and U87MG – luc2 cells. This decrease confirms the potential involvement of ASCT2 transporter in Azide – 1 uptake. On the other hand, an increase in the BLI signal was obtained in HepG2 – luc2 cells. This outcome likely came from the effect of gamma – glutamyl transferase which is an enzyme found in liver cancer cells (e.g. HepG2 cell) and catalyses the transfer of the gamma – glutamyl moiety to an acceptor to form
Antibiotics used in this experiment were Penicillin, Chloramphenicol, Tetracycline, and Erythromycin. Penicillin works by attacking bacteria’s peptidoglycan protein links and breaking down the cell wall. Penicillin works on gram negative bacteria but works better against gram positive bacteria. Chloramphenicol and Erythromycin work similarly by inhibiting bacteria’s protein synthesis, which inhibits overall bacterial growth. Both Chloramphenicol and Erythromycin work on both gram negative and gram positive bacteria. Chloramphenicol inhibits protein chain elongation by interfering with the peptidyl transferase activity of the bacterial ribosome at the 50S ribosomal subunit, that prevents peptide bond formation. Erythromycin also binds at the
SP-A shown the characterestics to enhances the uptake of M. tuberculosis by phagocytic cells such as macrophages and this is due to the up regulation of macrophage-mannose receptor mechanism (Gaynor et al., 1995). In the previous studies SP-D showed the different effects on phagocytosis of pathogens. SP-D showed the reduction in the uptake of M. tuberculosis by macrophages due to its assosiation with bacteria (Ferguson et al., 1999). SP-D CRD region binds to the cell wall components of M. tuberculosis such as mannosyl units (mannose caps) of lipoglycan and lipoarabinomannan (LAM) (Ferguson et al., 1999). It has also been shown that SP-D increases the uptake of Streptococcus pneumonia, Mycobacterium avium and E. coli (Kuroki et al., 2007; Brinker et al.,
Drug B: When the cells were exposed to drug B at two different concentrations (10uM and 10 µM), no change in activity was noticed and it was equal to basal activity. This clearly signals that B is an antagonist. Then we examine the effect of drug B when used in combination with drug A. The amount of cyclic AMP has decreased as the concentration of drug B increased from 10 uM to 10 µM while the concentration
Each subunit has a long extracellular N-terminus, followed by 4 transmembrane helices (M1–M4), which are separated by loops. The extracellular N-terminal domain comprises the agonist binding site [38, 49]. In the pentameric structure the channel pore is formed by a bundle of five M2 helices, each contributed by one the subunits. Residues within or in the vicinity of M2 are the basis of ion selectivity. The presence of negatively charged residues such as glutamate/aspartate near the cytosolic and extracellular transmembrane boundaries of M2 confer selectivity to cations whereas the positively charged/polar or neutral residues are those that confer anion
In this study three compounds structurally related to L – glutamine were designed with the aim of serving as the azide component of the Staudinger ligation which would react with the phosphine component TPP-CL1 to uncage luciferin. As shown in Fig. 4 the target compounds vary mainly in the position to which the azido group attached.
and inhibit or activate potassium channels (Poling et al., 1996) and so PUFA could be an
In addition to the above uses of pyrazole as therapeutic agent, it has recently been recognized to have modulatory effect on UPR, especially for the treatment of cancers and other diseases. The benzyl pyrazole derivative HSF1A, a small molecule activator of HSF-1, was identified in a yeast-based high-throughput screen (72). Induction of chaperones by HSF1A was shown to reduce protein misfolding and aggregation-mediated toxicity in cellular and fly models of polyQ-related diseases, and to activate HSF-1 in Drosophila and mammalian cells without inhibition of Hsp90 activity or causing proteotoxicity. Rather, HSF1A was suggested to interact with the cytosolic TCP-1 ring complex (TRiC). This proposed mechanism of action is of interest as TRiC