Synthesis and Biological Evaluation of Some New Pyrimidines free essay sample

General Papers ARKIVOC 2008 (xi) 131-141 Synthesis and biological evaluation of some new pyrimidines via a novel chalcone series Amit R. Trivedi, Dipti K. Dodiya, Naresh R. Ravat, and Viresh H. Shah* Department of Chemistry, Saurashtra University, Rajkot (Gujarat), India, Pin-360005 E-mail: [emailprotected] com Abstract In the present investigation ethyl 2-(4-carboxyphenylazo)acetoacetate 1 on condensation with various aromatic aldehydes in ethanolic NaOH solution yielded the corresponding chalcones 2a-j. These chalcones were further reacted with urea in the presence of base in ethanol, which led to the formation of pyrimidine derivatives 3a-j. The newly synthesized heterocyles were characterized on the basis of their chemical properties and spectroscopic data. All newly synthesized compounds were evaluated for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv. Keywords: Pyrimidine, antimycobacterial, Mycobacterium tuberculosis Introduction Tuberculosis (TB) is by far the most frequently encountered mycobacterial disease in the world. Although its incidence has diminished significantly in the industrially more developed countries; it remains a major public health problem in most of the developing nations. We will write a custom essay sample on Synthesis and Biological Evaluation of Some New Pyrimidines or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Tuberculosis is still the single largest infection having a high mortality rate and 0. 1 to 0. 3 percent of the population become infected each year in the developed countries. This year, 2 million people may develop the disease and 30 million may die worldwide (as per a WHO report). It is commonly known that Mycobacterium tuberculosis has developed resistance to the majority of the existing drugs. However, powerful new anti-TB drugs with new mechanisms of action have not been developed in the last forty years. In the developing countries, the annual infection rate is 20–50 times greater than in the developed countries and its high level shows little or no downward trend. It is expected that development of new effective anti-TB drugs will bring various outcomes viz: shortening the total duration of therapy, reducing the total expenditure and treatment of multiple drug resistant tuberculosis (MDR-TB) by single dosage regiment. ,3 In pursuit of achieving this goal, our research efforts are focused on the development of novel structural moieties having antimycobacterial properties. 4,5 Chalcones have various biological activities such as cytotoxic,5 ISSN 1551-7012 Page 131 Â © ARKAT USA, Inc. General Papers ARKIVOC 2008 (xi) 131-141 antimalarial,6 antioxidant,7 tyrosinase Inhibitory,8 anti-inflammatory,9 cancer chemopreventive9 and antibacterial. 10 Several pyrimidine deri vatives have wide varieties of usages and its nucleus is also present in vitamin B2 and folic acid. Pyrimidine heterocycles possessing hydroxyl group has a unique place in medicinal chemistry,11 and also plays a vital role in biological processes12, 13 as well as synthetic drugs. 14 Pyrimidines are associated with various therapeutic activities e. g. , anti-HIV,15 anti-tubercular,16 antitumor,17 antineoplastic,18 anti-inflammatory,19 diuretic,20 antimalaria,21 cardiovascular. 22 To the best of our knowledge, there has been no previous reports of analogous pyrimidines and parent chalcones as antituberculosis agents. However, there are numerous examples of nitrogen containing heterocycles being used to treat TB, for example Clofazimine, Isoniazid and Pyrazinamide. These compounds provide structural precedence that our chalcone and pyrimidine analogues may lead to the generation of novel anti-TB therapeutics. Herein the synthesis and in vitro antimycobacterial activity of novel chalcone and pyrimidine derivatives are described. Results and Discussion Chemistry The synthesis of chalcone and pyrimidine derivatives was performed following the steps shown in Scheme-1. In the initial step, chalcones (2a-j) were synthesized by condensing 2-(4carboxyphenylazo)acetoacetate23 1 with appropriate arometic aldehydes in dilute ethanolic sodium hydroxide solution at room temperature. The compounds (3a-j) were synthesized by reacting the appropriate chalcone with urea and potassium hydroxide in ethanol. The purity of the compounds was determined by TLC and elemental analysis. Spectral data (IR, 1H-NMR, 13C NMR and Mass) of all the newly synthesized compounds were in full agreement with the proposed structures. ISSN 1551-7012 Page 132 Â © ARKAT USA, Inc. General Papers ARKIVOC 2008 (xi) 131-141 O OH O OH + R-CHO NaOH/EtOH -C2H5OH -CO2 O N N O N N CH3 ? ? R (1) O (2a-j) OC2H5 O H2N KOH/EtOH NH2 O OH N R= Phenyl, 2-Hydroxyphenyl, 4- Hydroxyphenyl, 2-Nitrophenyl, 3- Nitrophenyl, 2-Chlorophenyl, 4-Methoxyphenyl, 3-Methoxy-4-hydroxy-phenyl, Styryl, 2-Furyl, N R (3a-j) N NH OH Scheme 1 The possible mechanism involved in the formation of dihydropyrimidine derivatives (3a-j) from the respective chalcones (2a-j) is shown below. ISSN 1551-7012 Page 133 Â © ARKAT USA, Inc. General Papers ARKIVOC 2008 (xi) 131-141 R H O H2 N R R NH2 R + O KOH Conjugated addition NH +H NH R OH H2N O R OH H2N O R H NH +H H R R NH -H2O O R N H NH R OH N H O R OH2 N H O HO R N N = O Biological screening Microbiology The in vitro activities of the synthesized compounds (2a-j 3a-j) for tuberculosis inhibition against the Mycobacterium tuberculosis H37Rv (ATCC27294) strain were performed using the micro plate alamar blue assay (MABA)24 method at TAACF. Compounds exhibiting fluorescence are tested in a BACTEC-460 radiometric system25, 26 and/or broth micro dilution assay. The activities are expressed as minimum inhibitory concentration (MIC, Â µg/mL) and are summarized in Table 1. Compounds demonstrating at least 90 % inhibition were re-tested at lower concentrations to determine the actual MIC, a value defined as the lowest concentration inhibiting ? 90% of the inoculums relative to the control. Antimycobacterial activity Twenty compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv using a BACTEC-460 radiometric system. Among the chalcones 2a-j and pyrimidines 3a-j, compounds 3d, 3e and 3g produced the highest efficacy and exhibited ;90% inhibition at 6. 5 ? Â µg/ml in the primary screen (Table 1). Compounds 2a-j, 3a-c, 3f and 3h-j exhibited ;90% inhibition against Mycobacterium tuberculosis at 6. 25 Â µg/mL (Table 1). These antimycobacterial data clearly indicated that the presence of 2-nitro, 3-nitro and 4-methoxy substitution on chalcone produced remarkable improvements in antitubercular activity. ISSN 1551-7012 Page 134 Â © ARKAT USA, Inc. General Papers ARKIVOC 2008 (xi) 131-141 Table 1. In vitro antimyc obacterial screening data of 2a-j 3a-j Sr. No. a 2b 2c 2d 2e 2f 2g 2h 2i 2j 3a 3b 3c 3d 3e 3f 3g 3h 3i 3j R Phenyl 2-Hydroxyphenyl 4- Hydroxyphenyl 2-Nitrophenyl 3- Nitrophenyl 2-Chlorophenyl 4-Methoxyphenyl 3-Methoxy-4-hydroxy-phenyl Styryl 2-Furyl Phenyl 2-Hydroxyphenyl 4- Hydroxyphenyl 2-Nitrophenyl 3- Nitrophenyl 2-Chlorophenyl 4-Methoxyphenyl 3-Methoxy-4-hydroxy-phenyl Styryl 2-Furyl Molecular Formula C17H14N2O3 C17H14N2O4 C17H14N2O4 C17H13N3O5 C17H13N3O5 C17H13N2O3Cl C18H16N2O4 C18H16N2O5 C19H16N2O3 C15H12N2O4 C18H16N4O3 C18H16N4O4 C18H16N4O4 C18H15N5O5 C18H15N5O5 C18H15N4O3Cl C19H18N4O4 C19H18N4O5 C20H18N4O3 C16H14N4O4 MIC Â µg/mL

The Do This, Get That Guide On Topics Argumentative Essay

The Do This, Get That Guide On Topics Argumentative Essay What's Really Going on with Topics Argumentative Essay Essay writing is a well-known practice in many schools and colleges across the united states. When it has to do with the middle school, the argumentative essay consists of moderate topics. Argumentative essays are a few of the best that you can write as a student. A variety of topics for college needs can use humor as the very best weapon to create a sheet of paper that would eventually draw more students to the writing, though they do not enjoy the ideas of writing. College professors see that students are well-trained and inspired to compose essays when asked to achieve that. Describe the college you would like to visit. College is for a high amount of study. Examine the list to choose the topic which can help you compose a creative essay for your middle school class. Figure out how funny argumentative essay topics can receive the interest of your tutor. You have to have skills to compose a great essay. If you're in a college and wish to compose an argumentative essay, you should decide on a subject of high importance. Remember your essay shouldn't be a string of jokes, it's a narrative it needs to have a start, middle and the end. The essay should have a little structure, unlike a normal essay. In this kind of situation, it's more convenient to locate ready-made essays and use them as an example. A definition essay can be hard to write. When you are finished with your essay, you must not just check it for spelling and grammatical errors, but nevertheless, it also has to be checked for logical fallacies. Argumentative essays utilize logic, facts, and reasoning to fix the victor. Regardless of the amount or type of research involved, they must establish a clear thesis and follow sound reasoning. The primary reason why somebody is writing an argumentative essay is to make an effort to persuade or sway another man or perhaps a group of men and women in your rightness in a particular theme. Topics Argumentative Essay - the Conspiracy There are invariably a wide variety of opinions on the field of technology, and here are our favourite things to consider on this issue. In choosing your topic, it's frequently a good idea to start with a subject which you already have some familiarity with. As soon as you have topics to select from, it is essential that you choose one which you can write about comfortably. Whenever you do, you're able to now write on topics which are going to be humorous to them. If you get to select your own topic, that's terrific. Therefore, the topic ought to be debatable! It must be interesting, the topic must be essential and finally the topic must be informative. Quite frequently, the very best topic is one which you truly care about, but you also will need to get ready to research it. Political issues are the ideal example. Argumentative essays look at an idea or a problem and present each side when creating a case for a single side specifically. A personal argumentative essay doesn't need to rely on research in order to earn a situation. Argumentative essays handle the counterargument. An argumentative essay is a certain kind of academic writing. It is a writing piece meant to persuade someone to think the way you do. It has a specific format that needs to be followed to blow the mind of the reader, and it is especially useful for students as well as the corporate while making strategic proposals. Then you ought to endeavour to select the right argumentative essay format. The thesis will reveal the reader precisely where you stand. Your thesis ought to be relevant so the post can use a structure that's flexible in order to fit in the shoes of the readers. Read the list and stay in mind that interesting topics are a proper way for an intriguing assignment. The topics must have two sides and they have to be quite intriguing. Make certain you give clear explanations of the things on your list also. Topics Argumentative Essay Secrets That No One Else Knows About One of the most significant hiccups in choosing funny argumentative essay topics is that comedy is a rather touchy field, and various people have various opinions of what comedy is about. Opt for a distinctive topic that others may not think of, and whatever you select, make certain you know a lot about it! Consider picking a topic that has been discussed by lots of individuals. Contradictive Your topic should stir a number of opinions among the general public.

How to Choose Topics For a History Research Paper

How to Choose Topics For a History Research PaperTo take a topic for amerhistory research paper, one must first decide what one's goals are. First of all, one should consider the purpose of his or her research. Then one should also consider the time frame that is appropriate for his or her research project. The ultimate goal of any research, especially in this age of multiple media is to contribute to the progress of human civilization.Secondly, one should determine the human population he or she would like to study. Before even selecting any of the options listed in the top-level list, one should keep in mind the period of time he or she would want to study. In choosing the period of time, one should not only look at the short-term aspects but also the long-term aspect of the study. It will be very helpful to select the period of time that is appropriate to the purpose of the project.Writing for a good topic can be extremely challenging. After reading the categories and discovering which ones are the most applicable, one has to actually write the paper. All of the writing skills that one has should be integrated with the capability to collaborate and share information effectively.The first thing to do is to choose the subject that interests you. There are many topics that one can choose from and some can even be more appropriate for certain individuals than others. For example, if the person does not want to engage in a debate where facts and arguments are debated, then he or she can choose another topic that focuses on myths and ideas. However, it is important to know that there are many topics that can be used as topics for amerhistory research paper. For example, if one is a math buff, then he or she can easily use math related topics as a topic for amerhistory research paper.When choosing the topics for amerhistory research paper, one should always consider the type of paper that one wants to write. For example, if one is writing a general history paper, t hen he or she should avoid using the term 'the' in his or her papers. Instead, he or she should always use 'a'an' whenever possible to make sure that everything flows nicely.The different types of papers are always the same. They include: essay, presentation, journal article, textbook, review, and thesis. One should always make sure that he or she is choosing topics that are appropriate for his or her writing style. Once the research is complete, one should continue to work on improving his or her writing style by avoiding common mistakes.One can always get the advice of experienced writers and read past articles that have been written by them. This will help one to better understand the way that amerhistory is written. These articles can help one understand the different types of papers that can be written and also how one can improve his or her own writing style.

Verbs For Writing Essay - Good Usage

Verbs For Writing Essay - Good UsageThere are several verbs for writing essay. The most common is 'to write'. In this article we will talk about a few more verbs for writing essay. One of the basic building blocks of any essay is the imperative verb, used to ask a question or to demand attention.One of the most commonly used imperative verb is 'to read'. It means reading the entire document for information and discerning it for ideas and facts. The most basic imperative verb for writing essay is 'to write'. In this form it does not mean writing the entire essay. A cursory glance through the document can suffice.Another imperative verb is 'to speak'. It means speaking out the entire document. A speaker expresses his opinions while talking. A speaker who writes his opinions is not an effective speaker. He may seem as though he is addressing you. However, he is actually addressing the document he is writing.The last imperative verb is 'to think'. It means thinking for some time in order to form ideas and speculations. An individual who writes takes his ideas and thoughts from a book. If you are going to write your thesis or dissertation, you will need to think of an argument, make an outline, organize your notes, work on a proper dissertation format, and basically plan everything you do.These three verbs for writing essay are the basics to starting a thesis or dissertation. While many people look for other ways to pass their time, I recommend you look up the three verbs for writing essay. Since the document is primarily about facts alone, the best way to get it out there is to write it. The next step is to read through it and form ideas for future essays. Some students like to write their own reports or dissertations, but the truth is that even if you think you are capable of doing it, you probably aren't.For those individuals who intend to become writers, the three imperative verbs for writing essay can be pretty useful. However, I would like to encourage you to follow the directions to a T. There are plenty of excellent, original texts out there. If you take the time to find them, you will be giving yourself a very important learning experience. However, if you do not, you may end up with a mediocre writing ability which will soon dissipate.So remember, don't worry so much about how you will end up with your final product. Learn how to write a thesis or dissertation, know the three verbs for writing essay and become a competent writer, so that you can enjoy your success and not be held back by a mediocre writing ability.

Sample of Scholarship Essay - How to Sample a Scholarship Essay About Yourself

Sample of Scholarship Essay - How to Sample a Scholarship Essay About YourselfIt's easy to sample a scholarship essay about yourself. In fact, it's easier than most of the other essay writing contests. But like most things in life, there are some important elements that you need to know. If you're not a student or do not have much experience with writing these kinds of essays, there are a few tips that will help you create a sample that will produce a winning essay.Write it in clear and concise language. Some scholarship essay samples contain multiple paragraphs that are too long and that end up being more tedious than useful. The way to avoid this is to write a short and to the point paragraph, before moving on to the next section. Be sure to take notes. Take lots of notes.Do not try to fit a few ideas or idea into one paragraph. Instead, include them all in a few sentences. One of the most popular scholarship essay samples includes one paragraph that explains your job experience, a nother paragraph that describes your academic achievements, and another that describes your religious beliefs. The idea is to fit as many different aspects of yourself into a single paragraph as possible.Look for the big idea. Scholarships for college students are awarded based on an idea. For example, if you're interested in earning a college degree, the competition is very high for scholarships. So, instead of just spending the majority of your essay on your academic accomplishments, look for a specific scholarship or college award that requires only a handful of college credits. Those who win most of the time are those who have a specific idea. If you do not know the best scholarship award for yourself, try searching online.See if you are able to communicate your ideas clearly. It's really important to stay focused on what you are trying to convey, rather than worrying about grammar or how you say it. As someone who has used many scholarships for college students, I would always read and re-read a sample of scholarship essay to make sure that my arguments were being conveyed correctly. Again, the best scholarship award will be one that works with your needs.Sample writing samples that you find online will often include one paragraph, one paragraph and one sentence. Those who have won most of the scholarships are those who have won the bulk of their essay in this format. However, if you aren't sure about the specifics of the scholarship award, ask around and see if anyone else has won it.Using sample writing samples to help you sample your scholarship essay will help you put the entire process together. As someone who has successfully used these to apply for hundreds of scholarships, I can tell you that it doesn't take long at all. If you follow these tips, you'll be writing a sample essay in no time.

The Strange Case Of Dr. Jekyll And Mr. Hyde Essays - Films, Novellas

The Strange Case Of Dr. Jekyll And Mr. Hyde The Strange Case of Dr. Jekyll and Mr. Hyde Robert Louis Stevenson in The Strange Case of Dr. Jekyll and Mr. Hyde is telling us that we fear the knowledge of our duality so we keep silent. We are afraid of the truth, about ourselves, so we stay quiet. Everyone has a part of himself or herself that they dont reveal to anyone. We are afraid to show it but when it comes out wed rather not talk about it. The author shows knowledge as a very important thing. Now I shall know you again, said Mr. Utterson. It may be useful. This quote is said when Mr. Utterson meets Mr. Hyde for the first time. Another quote that proves this is I wish to see or hear no more of Dr. Jekyll. Lanyon said this after he had seen Mr. Hyde turn into Dr. Jekyll and Mr. Utterson was asking him questions about Dr. Jekyll. Lanyon, you remember your vows: what follows is under the seal of our profession... Lanyon is about to find out about Dr. Jekylls secret. Another pattern that the author shows as being important is fear. Mr. Utterson and Mr. Enfield were walking together and seen Dr. Jekyll in his house. They were talking to him when all of a sudden he started to change into Mr. Hyde. When they saw this they looked at each other, both were pale and had an answering horror in their eyes. I am afraid, I think there has been foul play. Poole says this when he goes and talks to Mr. Utterson about Dr. Jekyll. Also when Mr. Utterson and Poole want to talk to Dr. Jekyll and ask for him but find out that Mr. Hyde is inside they swing an axe at his door. They hear a dismal screech, as of mere animal terror. Another way fear is shown is when Lanyon saw Mr. Hyde turn into Dr. Jekyll. O God and O God again and again. Lanyon said this after what he saw. Another major pattern is duality. You can see duality through out the whole book. One example is Mr. Utterson and Mr. Enfield. Mr. Utterson is very popular around town. He is also involved with the town. On the other hand Mr. Enfield was always quiet and didnt do anything around the town. But they were always together. Another example is Dr. Jekyll and Mr. Hyde. Dr. Jekyll was a smart, polite, and kind person. While Mr. Hyde was a person who liked to have fun. He was a rude and an evil person. This shows duality because Dr. Jekyll and Mr. Hyde was the same person. In the last chapter, the one that Henry Jekyll wrote he says Hence it came about that I concealed my pleasures. He wrote saying that he was holding back. Also in the same letter he says ...I saw that, of the two natures that contended in the field of my consciousness, I was both. In the same chapter he says he had just woke up and looked at his hand and saw something weird. It was the hand of Edward Hyde. Silence. Another thing he wanted us to know was important. I wouldnt speak of this note. Utterson said this when the guest compared the two handwritings of Dr. Jekyll and Mr. Hyde. Also When Dr. Jekyll wrote a note to Mr. Utterson excusing himself when he wouldnt see him The note said ...to lighten this destiny, and respect my silence. Lanyon left a letter to Mr. Utterson. When he opened it there was another letter that said not to be opened till the death or disappearance of Dr. Henry Jekyll. Mr. Utterson was temped to open it but he kept this silent too. Mr. Utterson and Mr. Enfield were walking and they seen Dr. Jekyll start to turn into Mr. Hyde. When they seen this Mr. Enfield only nodded his head, and both walked on once more in silence. Another example is when Poole takes Mr. Utterson a letter from Dr. Jekyll. After they read this Utterson puts this in his pocket and says I would say

Enlightenment Thematic Essay essays

Absolutism/Enlightenment Thematic Essay essays The Enlightenment was a time of greatness and advances in European History, but it can also be argued as a time of turmoil and destruction. During this time in European history, many great philosophers, or thinkers, thought of new ideas and methods of governing and social interactions to increase the prosperity of people. These ideas changes the way people felt about divine right authority by showing that individuals are born with inalienable rights. Arbitrary punishment was a problem during the reign of monarchs. Torture and suppression of ideas were a constant threat for both the philosophers and the citizens. A philosopher named Beccaria believed that reason could be used in determines the type and severity of punishment of a person. This was later used in the US Bill of Rights. Because of Beccarias idea, torture was reduced and abolished in Europe and North America. Another proposed reform was freedom of thought and expression which was one of the freedoms philosophers by the name of Voltaire fought for. Since his voice was constantly being suppressed by the monarchs, he proposed freedom of thought and expression, which later proved to play a vital part in the US Bill of Rights and the French Declarations of the Rights of Man and Citizen. In the US Bill of Rights, freedom of speech was influenced a great deal by this one idea by Voltaire. Consequences of the ideas of these two philosophers ultimately caused the development of the English parliament. A very big problem experienced thought Europe was a lack of equality for women. A philosopher by the name of Mary Wollstonecraft proposed a reform for womens equality. These ideas came from the standards that women possessed during the times; women should be wives and mothers, no more and no less. Because of this way of thinking, womens education and rights was given a low priority. Many people, both men and women attempted to reform this. This caused the crea...