Diketo Analogues and Their Significance

Diketo Analogues and Their Significance INTRODUCTION Medicinal chemistry is the branch of science, which has remarkable value for synthesis of novel drugs with intense therapeutic activity. It concerns with discovery, development, identification and interpretation of mode of action of biologically active compounds at molecular level. The molecular biological revolution and progressive mapping of human ‘genome’ have created a new biochemical and biostructural ‘world order.’1 These developments have provided new challenges and opportunities for drug research in general and drug design in particular. Pure organic compounds, natural or synthetic products are the chief source of agents for the cure, the mitigation or the prevention of disease today. The major objectives of the medicinal chemists are transformation of pathobiochemical and physiological data into a ‘chemical language’ with the aim of designing molecules interacting specifically with the derailed or degenerating processes in the diseased organisms. The development of chemotherapy during past 60 years constitute one of most important therapeutic advances in history of medicine and antimicrobial drugs are the greatest contribution of present century to therapeutics2. Potential therapeutic targets are being disclosed with increasing frequency and the exponential growth will continue during the next decades. In this situation there is a need for rapid and effective target validation and for accelerated lead discovery procedures. Organic chemists are increasingly directing their attention towards synthetic aspects of biomolecules and biologically active compounds, biosynthesized by plants and animals. Many important biochemical compounds and drugs of natural origin contain heterocyclic ring structures. Many of them are employed in treatment of many infectious diseases due to their specific activity, but their use in treatment is attributed to their inherent toxicity to various pathogens. DIKETO ANALOGUES AND THEIR SIGNIFICANCE Antibacterial The quinolones3 are well known synthetic antibacterial agents with di keto moiety some examples are Ciprofloxacin (1) Norfloxacin (2). Boteva4 et al synthesized some Halogen Substituted 4,5-dibenzoyl-1-phenyl-1H-pyrrole-2,3-dione derivatives (2-6) evaluated for Antibacterial Activity. Anti HIV The first report of a class of compounds that inhibit HIV integrase appeared in 1992. Aurin tricarboxylic acids and derivatives were determined to inhibit 3’ processing of viral cDNA with moderate iC50 values of 10-50micromolar. Thus the 1st pharmacophore with integrase inhibitory activity was determined i.e. aromatic rings with multiple hydroxyl substituents positioned on same ring or present close together in a 3D space if rings stack on top of each other. Since then considerable amount of work has been carried out in developing potential inhibitors of integrase taking the above compounds as leads. Presently there is only one FDA approved drug used as integrase inhibitor i.e. Raltegravir or Isentress, (7) approved in 2007. Elvitegravir (8) is another potential integrase inhibitor which is in phase III clinical trial5. THIOPHENE ANALOGS AND THEIR SIGNIFICANCE Thiophene (9) and its derivatives are an important class of heterocyclic compounds possessing broad biological activities, such as anti-inflammatory6, analgesic6, antioxidant7, antitubercular8, antidepressant9, sedative9, antiamoebic10, oral analgesic11, antimetabolite12, and antineoplastic properties13. Antimicrobials Thiophene analogues have been known as antibacterials. In the year 2007 Stephane et al14 reported the synthesis and antibacterial activity of arylbenzothiophenes (10) and diarylthiophenes. (11) (10) (11) In the year 2010 Kavitha P N et al15 reported the antimicrobial activity of 3- amino-2- mercapto-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-ones (12-17) by using B. subtilus, K. pneumonia and A. niger. Desai Akshay et al16 reported the synthesis of 2-thiophene-2- ethylthioureido-4- morpholino-6-(aryl) ureido-s-triazines.(18-23) These analogs were evaluated for their antimicrobial activity using S. typhi, C. albicans. Bhuiyan Md. Mosharef Hossain et al17 reported synthesis of 4-hydrazino-2- mehylthio-5-ethyl-6- methylthieno [2,3-d] pyrimidine (24) which is evaluated as antimicrobial agent by using B.cereus, V.cholerae, A.alternate. (24) Shiradkar M. et al18 reported synthesis of N-[3-(substituted)-7H- [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazine / thiadiazol-4,5,6,7- tetrahydrobenzo[b] thiophenes (25-32) as good antimicrobial agents by using E.coli, S.aureus, A.nigar. Ahmed M. M. et al19 reported synthesis of 4-(substituted)-7-cyano- 6-phenyl aminothieno [3,2-d] pyrimidins (33-34) and evaluated as good antimicrobial agents by using B.subtilis and St.aureus, compared with reference drug Amoxicillin. The 6-methyl-2-phenyl-3-(substituted)-3H-thieno[3,2-d] pyrimidin-4-ones (35-38) has been reported by Chander Mohan et al20 and evaluated for antimicrobial activity by using B. subtilis, E.coli, P.aeruginosa compared with standard drug Ciprofloxacin. Bhuiyan Md. Mosharef Hossain et al21 reported synthesis of thieno[3,2-e] imidazo[1,2-c] pyrimidin-2(3H)ones (39) which was evaluated for antimicrobial activity against B. cereus, S.typhi and A.alternatacompare to reference drugs Ampicillin with Nystatin. (39) Shetty Nitin kumar et al22 reported synthesis of 8,9,10,11-tetrahydro[1]benzothieno[3,2-e] [1,2,4]triazolo [1,5- c]pyrimidine -8-ones (40-42) and evaluated for antibacterial activity against B. subtilis comparable to ampicilin. References : Larsen PK, Liljefors T, Madsen U, editors. Text book of drug design and discovery. 3rd ed. London: Taylor Francis; 2002. Rang HP, Dale MM, Ritter JM Pharmacology, 4th edition Churchill Livingstone, Edinburgh, 1999: 648 Wilson Gisvold, Textbook of Organic Medicinal and Pharmaceutical Chemistry, 10th edition, Lippincott publication Philadelpia 196-203. A.A Boteva, O. P. Krasnykh, S.S.Dubrovina, M. I. Vakhrin, E.B. Babushkina, T.F. Odegova, I.V. Solova, Pharm Chem J , 2008, 42 (8), 12-15. Vincenzo Summa AlessiaPetrocchi, Fabio Bonelli, BenedettaCrescenzi, Monica Donghi, Marco Ferrara, Fabrizio Fiore, Cristina Gardelli, Odalys Gonzalez Paz, Daria J. Hazuda, Philip Jones, Olaf Kinzel, Ralph Laufer, Edith Monteagudo, Ester Muraglia, EmanuelaNizi, Federica Orvieto, Paola Pace, Giovanna Pescatore, Rita Scarpelli, Kara Stillmock, Marc V. Witmer, and Michael Rowley, J. Med. Chem. 2008, 51, 5843–5855. F.M. Moghaddam, H.Z. Boinee, An efficient and facile one-step synthesis of highly substituted thiophenes, Tetrahedron 60 (2004) 6085-6089. K.I. Molvi, M. Mansuri, V. Sudarsanam, et al., Synthesis, anti-inflammatory, analgesic and antioxidant activities of some tetrasubstituted thiophenes, J. Enzyme. Inhib. Med. Chem. 23 (2008) 829-838. M.K. Parai, G. Panda, V. Chaturvedi, Y.K. Manju, S. Sinha, Thiophene containing triarylmethanes as antitubercular agents, Bioorg. Med. Chem. Let. 18 (2008) 289-292. W. Wardakhan, O. Abdel-Salam, G. Elmegeed, Screening for antidepressant, sedative and analgesic activities of novel fused thiophene derivatives, Acta. Pharm. 58 (2008) 1-14. S. Sharma, F. Athar, M.R. Maurya, A. Azam, Copper(II) complexes with substituted thiosemicarbazones of thiophene-2-carboxaldehyde: synthesis, characterization and antiamoebic activity against E. histolytica, Eur. J. Med. Chem. 40 (2005) 1414-1419. O. F. William, Principles of Medicinal Chemistry, 3rd. ed., Lippincott Williams Wilkins Publication, Philadelphia, 1989. A.A. Sagardoy, M. J. Gil, R. Villar, et al., Benzo[b]thiophene-6-carboxamide 1,1-dioxides: Inhibitors of human cancer cell growth at nanomolar concentrations, Bioorg. Med. Chem. 18 (2010) 5701-5707. A.A. Fadda, E. Abdel-Latif, R.E. El-Mekawy, Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives, Eur. J. Med. Chem. 44 (2009) 1250-1256. Jeremie Fournier dit Chabert, Beatrice Marquez, Luc Neville, Lionel Joucla, Sylvie Broussous, Pascale Bouhours, Emilie David, Stephane Pellet Rostaing, Bernard Marquet,a Nicole Moreaub and Marc Lemairea, Synthesis and evaluation of new arylbenzo[b]thiophene and diarylthiophene derivatives as inhibitors of the NorA multidrug transporter of Staphylococcus aureus, Bioorganic Medicinal Chemistry 15 (2007) 4482–4497. Kavitha PN, Vijayanthimala P, Saravanan J, Mohan S. Research Journal of Pharma- ceutical, Biological and Chemical Sciences, 2010; 1(2):124-130. Desai A, Mahajan HD, Ind Jour Chem, 2007; 46(B):1169-1173. Ahmed MM, Farha FM; Jordan Journal of Chem, 2008; 3(3):223-232. Shiradker M, Kale R. Ind Jour Chem, 2006; 46(B):1009-1013. Ahmed MM, Farha FM; Jordan Journal of Chem, 2008; 3(3):223-232. Mohan C, Bhargava G, Bedi PMS. J Life Sci, 2009; 1(2):97-101. Bhuiyan MH, Rahman KM. Acta Pharm., 2006; 56: 441-450. Nitinkumar SS, Lamani RS, Khazi IAM. 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He tendency for human beings to copy one another is shown in the popularity of fashion and goods Essay

The tendency for human beings to copy one another is shown in the popularity of fashion and goods. Agree or disagree. Agree – Economic urge – Easy to copy Disagree – Not easy to copy due to complicated procedures – Other fields are easier to be copied Fashion and goods are becoming more similar between brands. Some people think that manufacturers are copying ideas of each other in such products while others claim that this is hardly necessarily reflected mostly in fashion and goods. I believe that in any field, people can copy from other and sometimes, fashion and consumer goods are far from easy imitation. First of all, it is thought that copying the style of fashion and goods is easier than other types of imitation. Just a glance at design is sufficient enough to provide other competitive brands to follow and manufacture right after the original item comes into being. Nevertheless, people’s desire is to enjoy products with good appearance and quality at the same time. Despite the copying trend of outstanding appearance, if the quality of products is below expectation of consumers, for instance, short durability and high price, the latter ones will shun away these items soon. Second of all, people mostly need goods in their daily life. The rate of consumption in daily goods adds up to billions of dollars for producers, which motivates them to copy each other. Yet, when it involves the assembly line and advanced technological applications, it is far from easy to follow suit. Technological goods need expertise, significant investment and long-term research. Hence, though goods may look like each other, they are rarely products of pure emulation and mass- consumed. Chinese products, for instance, in spite of being believed to be of lower price and copy others in the world, are still not as attractive as original ones as created in America and Japan due to their unfashionable design and short-time durability. In addition, copying trend is noticeable in other fields. In arts, the musical style of one nation borrows greatly from that of other countries to enrich cultural heritage of each nation while products of high intellectuality such as writing styles are somehow similar to each other. Even in choice of life, when a person has little inkling about what he or she does in life, it is more likely that he or she will travel the same journey as predecessors to be on the safe side. When it comes to work environment where competition is higher, to ingratiate oneself with bosses, employees are possible to copy ideas of others, which actually proves easier than to imitate the complicated business models to generate fashion designs or consumer goods. â €“ written by lena pham-

To What Extent Can Gatsby Be Considered a Tragic Hero

To what extent can Gatsby be considered a tragic hero? Before we can judge if Jay Gatsby is a tragic hero, we should look at the exact deï ¬ nition of a tragic hero. According to the classic deï ¬ nition, a tragic hero is a  «great or virtuous character in a dramatic tragedy who is destined for downfall, suffering, or defeat »1, and Oedipus, from the Greek Legends, is deï ¬ ned as the classic tragic hero. So, is Gatsby then a classic tragic hero, by deï ¬ nition? ! Even if the book itself is called  «Great Gatsby », is Jay really great? From the text, we know that he came from a poor family, and made his fame and money through illegal business, and created a fake world of his own surrounding his reality, because he never accepted reality as it was.†¦show more content†¦Gatsby has created his  «greatness », but has none of his own. So, he is not a hero by classical deï ¬ nition, not quite, just because all that he is, his greatness, is in fact a masterful illusion. ! Is Gatsby destined for downfall? Clues can be found all over the novel, in descriptions of Gatsby, and Nick’s portrayal of him. Firstly, Nick realises straight away that Gastby is lying about his past and his trips to India, which suggests that Gatsby isn’t that much of a good liar, and Gatsby doesn’t realise this, because he has made all his dreams reality. Also, the description o f Gatsby in chapter 6 gives us suggestions on why Gatsby can never be satisï ¬ ed with his life:  «...these reveries provided an outlet for his imagination; they were a satisfactory hint of the unreality of reality, a promise that the rock of the world was founded securely on a fairy’s wing »2. This quote is a perfect illustration of how Gastby views life. The fairy mentioned is has a slightly sarcastic feel, it’s almost as if Gastby’s mind is of a child - that everything around him is perfect, and nothing can inï ¬â€šuence him. But, such an oblivious approach to life cannot be secure or everlasting. Every dream changes, and every lie comes through sometime. Gatsby has to understand that he cannot live in his own fantasy, and that otherShow MoreRelatedTo What Extent Can Gatsby Be Considered a Tragic Hero?1023 Words   |  5 PagesTo what extent can Gatsby be considered a tragic hero? Before we can judge if Jay Gatsby is a tragic hero, we should look at the exact deï ¬ nition of a tragic hero. According to the classic deï ¬ nition, a tragic hero is a  «great or virtuous character in a dramatic tragedy who is destined for downfall, suffering, or defeat »1, and Oedipus, from the Greek Legends, is deï ¬ ned as the classic tragic hero. So, is Gatsby then a classic tragic hero, by deï ¬ nition? ! Even if the book itself is called  «Great Gatsby »Read MoreEssay Prompts4057 Words   |  17 PagesQUESTIONS 2004 (Form A): Critic Roland Barthes has said, â€Å"Literature is the question minus the answer.† Choose a novel or play and, considering Barthes’ Observation, write an essay in which you analyze a central question the work raises and the extent to which it offers any answers. Explain how the author’s treatment of this question affects your understanding of the work as a whole. Avoid mere plot summary. You may select a work from the list below or another novel or play of comparable literaryRead MoreANALIZ TEXT INTERPRETATION AND ANALYSIS28843 Words   |  116 Pageslinguistic commentary in which the reader explains what the text reveals under close examination. Any literary work is unique. It is created by the author in accordance with his vision and is permeated with his idea of the world. The reader’s interpretation is also highly individual and depends to a great extent on his knowledge and personal experience. That’s why one cannot lay down a fixed â€Å"model† for a piece of critical appreciation. Nevertheless, one can give information and suggestions that may prove