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Synthesis of Quaternary Ammonium Based New Analgesic, Anti- Inflammatory and Antipyretic Drugs

Thesis Info

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External Link

Author

Ullah, Nasir

Program

PhD

Institute

University of Peshawar

City

Peshawar

Province

KPK

Country

Pakistan

Thesis Completing Year

2012

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/2109

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727495330

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The carboxylic acid group (-COOH) present in most commercial NSAIDs is thought to be partly responsible for the gastric toxicity associated with the long-term administration of these compounds. The goal of the present research was to determine if new NSAID derivatives devoid of acidic moieties would retain the anti- inflammatory activity while exerting a lower degree of gastric toxicity compared to the corresponding parent NSAID. In this regard, we replaced the carboxylic acid group in aspirin, ibuprofen, flurbiprofen, and naproxen with a series of quaternary ammonium moieties, and the resulting water-soluble NSAID derivatives were tested for anti-inflammatory and ulcerogenic activity in vivo. Results of our investigation showed that replacement of quaternary ammonium moieties for the carboxylic acid group present in NSAIDs, yielded potent anti-inflammatory molecules without stomach ulceration when administered orally to rats. Among the new compounds, N- (2-hydroxyethyl)-2-(6-methoxynaphthalen-2-yl)propan-1-aminium chloride (a naproxen derivative) was the most potent anti-inflammatory agent (65.28% inhibition of inflammation at 6.4 mg/kg); however, unlike the reference compound naproxen (ulcer index = 108.7), N-(2-hydroxyethyl)-2-(6-methoxynaphthalen-2-yl)propan-1- aminium chloride did not produced gastric ulcers (Ulcer index = 0) when administered orally at equimolar doses (0.17mmol). These results suggest that the carboxylic acid group present in commercial 2-phenylpropionic acid NSAIDs is not an essential requirement for anti-inflammatory activity in vivo, and offers a new concept in drug design by using water-soluble ammonium moieties instead. Derivatives of salicylic acid were screened for analgesic, anti-inflammatory and antipyretic activities, and acute toxicity. The result of this study indicated that these compounds possess dose dependent statistically significant analgesic, anti- inflammatory and antipyretic properties, compared to aspirin, without causing gastric ulceration and acute toxicity.
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وصیتِ علم و عمل

وصیتِ علم و عمل
وجود ِ انسانی کے ارتقا کی تاریخ کو نظر ِ غائر سے دیکھا جائے تو اس کی تمام تر ترقی ’’ علم ــ‘‘ کی مرہون منت ہے۔علم ہی وہ اکائی ہے جس میں تہذیب و تمدن اور تربیت کے سوتے پھوٹتے دکھائی دیتے ہیں۔علم کی خصوصیت کی وجہ سے انسان اشرف المخلوقات ہے اس کے سبب سے اسے فرشتوں پر فضیلت ملی اور اسی کی بدولت خلافت کا تاج سر پرسجا۔حد تو یہ ہے کہ پہلی وحی کا آغاز ہوا۔ارشاد ربانی ہے ترجمہ:۔ ’’اپنے پروردگار کے نام سے پڑھ جس نے انسان کو جمے ہوئے خون سے پیدا کیا‘‘۔یہ بھی ارشاد ر بانی سنتے چلیے ۔ ترجمہ:۔’’ اللہ تم میں سے ایمان والوں اور علم والوں کے درجات بلند فرماتا ہے‘‘۔قرآن کریم میں ہی اللہ پاک نے اپنے نبی مکرم ﷺ کو یہ دعا عطا فرمائی ۔ترجمہ:۔ ’’کہو ،اے میرے رب میرے علم میں اضافہ فرما‘‘۔ حدیث شریف میں آتا ہے کہ ’’ علم حاصل کرناہر مسلمان (مرد اور عورت)پر فرض ہے‘‘ یہی وہ علم ہے جس کی افضلیت کے پیش نظر حضرت علی کرم اللہ وجہ فرماتے ہیں’’ ہم اللہ تعالیٰ کی اس تقسیم پر راضی ہیں کہ اس نے ہمیں علم عطا کیا اور جاہلوں کو دولت دی کیوں کہ دولت تو عنقریب فنا ہوجائے گی اور علم کو زوال نہیں‘‘۔
تاریخ انسانی میں ایک خواہش جو اپنے تمام تر مدارج سمیت جھلک رہی ہے وہ یہ ہے کہ ہر شخص اپنی جدا گانہ شناخت اور منفرد پہچان کا متمنی ہے اور اس خواہش کی تکمیل کے لیے مثبت اعمال و افعال بروئے کار لا کر ہی ازلی و ابدی پہچان تک رسائی حاصل کر لینا اصل شناخت اور پہچان ہے ۔اہل علم جانتے ہیں کہ یہ اسی وقت ممکن ہے جب علم کواوڑھنا بچھونابنا لیا جائے اور فضل باری تعالیٰ...

اسلامی ریاست میں غیر مسلم رعایا کے حقوق

“Minority” is a word which is considered a challenge for any political system. This article discusses how a certain political system deals with the idea and rights of a minority. If a minority enjoys the privileges in a society that political system is considered as perfect. Islam, the revealed religion, has not overlooked the status of a minority. Rights of a minority is one of the top priorities in Islam. This article brings to the fore the very status which Islam gives to the minorities and which they enjoyed while living in the Islamic poltical and social set up. Islam not only gives minorities the right to live in an Islamic Society, but also gives them protection. The word “Dhimmis” gives minorities the protection in an Islamic society which they never entertain in their own society. Whether it was the time of the Holy Prophet, the Abbasid’s or Umayyad, everywhere in the Islamic society they enjoyed not only as minorities but also they were allowed to build churches, join Islamic forces and to become viziers, etc. It clearly reveals that Islam is a religion of peace that not only gives good tidings to the believers but aslo to the minorities who live among them. This article is a small replica of what the minorities enjoyed in the Islamic society.

Physiological and Biochemical Responses of Wheat Triticum Aestivum L. to Boron under Saline Conditions

High levels of boron (B) and salinity are a serious constraint to crop production around the world. Cropping on saline and B toxic land is restricted by the low tolerance of agricultural crops to these abiotic factors. Prospects for improving B and salt tolerance in wheat can only be made possible by advance research. Frequently, B and salt occur together, however, it is unknown whether the interactions of B and salt increase or decrease the tolerance of a plant to both of these stresses. Low concentration of B is essential to plant growth and may limit the plant growth and development in excess quantity especially under saline conditions. Limited information was available regarding the effect of B on wheat (Triticum aestivum L.) under saline conditions. The present studies were conducted to investigate the interactive effects of salinity and B on growth, yield, physiological and biochemical responses of wheat. Hydroponics and pot studies were conducted at various B levels under normal and saline conditions. First, twelve wheat genotypes were screened out against various levels of salinity (control, 100, 200 mM NaCl) in solution culture. The SARC-I and Sehar-2006 were found as tolerant to salinity whereas, Kohistan-90 and MH-97 were categorized as salt-sensitive wheat genotypes. In a second study, these four wheat genotypes (differing in salt tolerance, selected from study-I) were grown at control, 0.5, 1.0 and 1.5 mM B in hydroponics under non-saline and saline conditions (100 and 200 mM NaCl). The data of physical and biochemical characteristics showed that the decrease in root and shoot fresh and dry weights were more in salt-sensitive (Kohistan-90 and MH-97) than in salt-tolerant (SARC-I and Sehar-2006) wheat genotypes. Salt-tolerant wheat genotypes accumulate less B and Na+, while more K+ in their leaves than the salt-sensitive wheat genotypes. Salinity resulted in higher reduction of shoot growth while B toxicity affected root growth more than the shoots growth. The reduction in plant growth by combined salinity and B toxicity was less than the sum of reduction caused by individual salinity and B toxicity. Salinity reduced B toxic effects and B toxicity reduced salinity stress in wheat plants. Regarding the physiological responses like photosynthetic rate (PR) stomatal conductance (SC) and transpiration rate (TR) were also decreased with salinity and toxic levels of B, and salt-tolerant genotypes showed better response regarding PR, SC and TR than salt-sensitive genotypes. Moreover, the activity of superoxide dismutase (SOD) and catalase (CAT) was found higher in tolerant genotypes than sensitive ones in the presence xix of individual and combined salinity and B stresses. In a pot study, the effects of various levels of B (control, 2.5, 5 and 7.5 mg kg-1) on the growth, yield, physiological and biochemical processes of two wheat genotypes (differing in salt-tolerance, selected from study-II) in normal as well as saline (electrical conductivity i.e., EC = 10 and 20 dS m-1) soils were investigated. The plant height, straw and grain yields of wheat were increased at lower level of B and decreased at toxic B rates in both normal and salt-affected soils. In comparison with salt-tolerant SARC-I, the salt-sensitive MH-97 showed more reduction in growth, yield and physiological attributes in the presence of individual as well as combined salinity and B toxicity. Leaf B and K+ concentration decreased under saline conditions, while leaf Na+ concentration increased. Salt-tolerant genotype accumulated less Na+, Cl- and B and more K+ in leaves. The PR, TR and SC decreased, while the activity of SOD and CAT increased with increasing salinity and B stresses either alone or in combination and that were found higher in tolerant genotype as compared to sensitive one. Regarding Pakistani conditions, wheat genotype i.e., SARC-I was proved as most promising one under saline and B toxic conditions and can be directly used by farmers or can be used for the development of more salinity and B tolerant wheat genotypes by the breeders. The impacts of soil salinity and B toxicity on the carbohydrate partitioning, growth and ionic composition of two Australian wheat varieties (i.e., Halberd, salt-tolerant and Westonia, salt-sensitive) were explored, in another glasshouse experiment conducted at Murdoch University, Perth-Australia. The results showed that salt-tolerant variety accumulated more Na+, B and Cl- in their leaf sheath and kept their leaf blades free of these toxic ions than sensitive variety. Water soluble carbohydrates (WSCs; such as glucose, sucrose, fructose and fructans) concentration increased in response to individual and combined stresses of salinity and high B in leaf blade of both tolerant and sensitive varieties but the increase was higher in tolerant variety than the sensitive one. The concentration of WSCs in leaf sheath of salt-tolerant Halberd wheat variety was increased in response to stress conditions but remained low in salt-sensitive Westonia. In squat, it can be concluded from the above Ph.D. research work that salinity and B toxicity showed antagonistic relationships for their effects on wheat growth, yield, physiological and biochemical responses. The highly tolerant and low B accumulating wheat genotype can be a wise option for normal and salt-affected B-toxic conditions.