Complexity of drugs

Natural products are currently underrepresented in the small-molecules drug library largely because of their extremely low yields, lower supply of natural resources and complex structures posing greater difficulty for structural modification and practical synthesis. Despite the challenges natural product based drugs continue to make impact in drug discovery.

223p spiritedaway36 26-11-2021 15 2   Download

The development of drug delivery systems in the last several decades has provided a variety of methods including the synthesis new Pt(II), Pt(IV) complexes, the incorporation of drugs into liposome’s, lipid emulsions, and polymeric micelles to reduce side effects, to increase their solubility, and to prolong circulation time as well. Camphor has bioactivity, it has been used in traditional medicine from time immemorial.

6p abcxyz123_02 03-03-2020 9 1   Download

At the end of the session, participants should be able to: understand the complexity of drugs and classification of the drugs, define the society and understand the relation between drugs and society, understand the various interventions that can be used to mediate the impact of drugs on society.

43p tuoihaimuoi32 19-06-2014 73 5   Download

The K103N substitution is a frequently observed HIV-1 RT mutation in patients who do not respond to combinationtherapy. The drugs Efavirenz, MSC194 and PNU142721 belong to the recent generation of NNRTIs characterized by an improved resistance profile to the most common single point mutations within HIV-1 RT, including the K103N mutation. In the present study we present structural observations from Efavirenz in complex with wild-type protein and the K103N mutant and PNU142721 and MSC194 in complex with the K103N mutant.

8p system191 01-06-2013 41 4   Download

Single-crystal X-ray structure determinations of the complex between the minor-groove binder distamycin and d(GGCCAATTGG) reveal two 1 : 1 binding modes which differ in the orientation of the drug molecule in the minor groove. The two crystals were grown from different crystallization conditions and found to diffract to 2.38 and ˚ 1.85 A, respectively. The structures were refined to completion using SHELXL-93, resulting in a residual R factor of ˚ 20.30% for the 2.38-A resolution structure (including 46 ˚ water molecules) and 19.74% for the 1.

10p system191 01-06-2013 29 5   Download

The structure–activity relations of a series of synthetic phenoxazone drugs with aminoalkyl side chains of variable length and different terminal groups were investigated by examining their biological activity and DNA complexation affinity. Biological activitywas determined fromtheir ability to induce apoptosis and cell cycle perturbations (activation of cell cycle checkpoints) using the human malignant MOLT-3 cell line. The thermodynamic parameters of drug– DNA complexation were determined by differential scan-ning calorimetry....

8p tumor12 20-04-2013 37 4   Download

p38 Mitogen-activated protein kinase alpha (p38 MAPKa) is a member of the MAPK family. It is activated by cellular stresses and has a number of cellular substrates whose coordinated regulation mediates inflammatory responses. In addition, it is a useful anti-inflammatory drug target that has a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a number of transcription factors as well as protein kinases in its catalog of known substrates.

15p fptmusic 11-04-2013 42 3   Download

The structure of the complex between the minor groove binder netropsin and d(GGCCAATTGG) was determined via single-crystal X-ray tech-niques. The structure was refined to completion usingrefmac5.1.24, result-ing in a residual R-factor of 20.0% (including 68 water molecules). Using crystal engineering and cryocooling techniques, the resolution could be enhanced to 1.75 A ˚ , resulting in an unambiguous determination of the drug conformation and orientation.

11p fptmusic 11-04-2013 34 2   Download

The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PRV82Aand PRL90M,have been determined in complex with the antiviral drug, indi-navir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (Ki)of PRV82Aand PRL90Mwas 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10–15%, in theirkcat /Kmvalues relative to PR. ...

9p dell39 03-04-2013 28 3   Download

Thymidine kinases have been found in most organisms, from viruses and bacteria to mammals.Ureaplasma urealyticum(parvum), which belongs to the class of cell-wall-lacking Mollicutes, has no de novosynthesis of DNA precursors and therefore has to rely on the salvage pathway. Thus, thymi-dine kinase (Uu-TK) is the key enzyme in dTTP synthesis.

8p dell39 27-03-2013 33 2   Download

The anticancer agents cisplatin and oxaliplatin are widely used in the treat-ment of human neoplasias. A genome-wide screen inSaccharomyces cere-visiae previously identified PPH3and PSY2among the top 20 genes conferring resistance to these anticancer agents. The mammalian ortho-logue of Pph3p is the protein serine⁄threonine phosphatase Ppp4c, which is found in high molecular mass complexes bound to a regulatory subunit R2.

13p inspiron33 25-03-2013 39 4   Download

Malaria is caused by protozoan parasites of the genusPlasmodiumand is a major cause of mortality and morbidity worldwide. These parasites have a complex life cycle in their mosquito vector and vertebrate hosts. The pri-mary factors contributing to the resurgence of malaria are the appearance of drug-resistant strains of the parasite, the spread of insecticide-resistant strains of the mosquito and the lack of licensed malaria vaccines of proven efficacy.

10p media19 04-03-2013 35 2   Download

Many protein substrates of caspases are cleaved at noncanonical sites in comparison to the recognition motifs reported for the three caspase sub-groups. To provide insight into the specificity and aid in the design of drugs to control cell death, crystal structures of caspase-7 were determined in complexes with six peptide analogs (Ac-DMQD-Cho, Ac-DQMD-Cho, Ac-DNLD-Cho, Ac-IEPD-Cho, Ac-ESMD-Cho, Ac-WEHD-Cho) that span the major recognition motifs of the three subgroups.

14p media19 04-03-2013 38 4   Download

The two-component NS2B–NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro.

12p vinaphone15 25-02-2013 33 4   Download

Small molecules that activate the transcriptional function of wild type p53 have proved active as anti-cancer drugs in preclinical models and are now entering clinical trial. The complexity of the upstream p53 signaling pathway offers many targets for the devel-opment of such activators and the action of Mdm2 inhibitors, kinase inhibitors, sirtuin inhibitors and low doses of actinomycin D will be described among other examples.

3p viettel02 22-02-2013 43 4   Download

The structural and kinetic effects of amprenavir (APV), a clinical HIV pro-tease (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug resistance. Crystal structures of the APV complexes at resolutions of 1.02–1.85 A ˚ reveal the structural changes due to the muta-tions.

16p viettel02 19-02-2013 41 2   Download

Candidainfections have become an increasingly significant problem, mainly because of the widespread nature ofCandidaand drug resistance. There is an urgent need to develop new classes of drugs for the treatment of oppor-tunistic Candidainfections, especially in medically complex patients.

11p cosis54 05-01-2013 36 3   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains...

11p toshiba15 24-10-2011 55 3   Download

Conclusion: Toward a Science of Implementation Public-health strategies draw largely on quantitative methods—from epidemiology and biostatistics, but also from economics. Clinical practice, including internal medicine, draws on a rapidly expanding knowledge base but remains focused on individual patient care; clinical interventions are rarely population-based. In fact, neither public-health nor clinical approaches alone will prove adequate in addressing the problems of global health.

6p tubreakdance 26-11-2010 102 6   Download

Recent advances in mass spectrometry have rendered it an attractive and versatile tool in industrial and academic research laboratories. As a part of this rapid growth, a considerable body of literature has been devoted to the application of mass spectrometry in clinical studies. In concert with separation techniques such as liquid chromatography, mass spectrometry allows the rapid characterization and quantitative determination of a large array of molecules in complex mixtures.

36p bigbaby87 03-09-2010 114 12   Download