شیخ خضری
شیخ خضری کی وفات، شیخ خضری کا جو مصر کے مشہور علماء میں تھے، پچھلے مہینہ میں انتقال ہوگیا، یہ مفتی عبدۂ کے صحبت یافتہ تھے، اور وہاں کی جامعہ مصریہ میں اسلامی تاریخ کے پروفیسر رہ چکے تھے اور کئی مفید کتابوں کے مصنف تھے، جن میں سے ان کی تاریخ اسلام سب سے مشہور کتاب ہے، جس کی تلخیص یا ترجمہ جامعہ ملیہ میں ’’تاریخ امت‘‘ کے نام سے کیا گیا ہے، جو عام طور سے نہایت پسند کی گئی اور بے حد مقبول ہوئی۔
(ریاست علی ندوی، جون ۱۹۲۷ء
The aim of this research is to assess the impact of social capital on civic engagement. The quantitative method was applied to measure impact of independent variables on dependent variable. The survey instrument was applied to collected data from undergraduate student of four general Universities of Pakistan. The partial least squares structural equation modeling (PLS-SEM) approach was applied to measure impact of bridging, bonding social capital and trust on civic engagement. Results indicate that bonding social capital and trust have strong association with civic engagement, however, association between bridging social capital and civic engagement was found insignificant. The analyses indicate that it is a basic requirement to bring immediately policy reforms in context of youth development and create more opportunities for youth to engage in the social and structural development of society.
The chemistry of life has been extensively and effectively elaborated by organic chemists. No doubt, all the fields of science are struggling for the benefit of human beings and the chemists are well known in this regard. The organic or medicinal chemists are the main worker of improving the health. A number of compounds have been synthesized in search of new drug candidates by the orgnic chemists and also they have been successful up to much extent in this regard. The importance of this process can be realized from the increasing inactivity of the running drugs against different diseases. Hence the synthesis of new molecules in search of new drug candidates against different diseases is an ever green process. This was the motivating aspect of the literature survey of synthetic chemistry which encouraged us to design new molecules and evaluate their biological potential. The bioactivity potential of some heterocyclic moieties (as discussed in introduction and review of literature) prompted has to design such type of molecules which bear more than one heterocyclic moieties. These considered heterocyclic moieties included piperidine and 1,2,4-triazole. The aim of submerging different heterocyclic functionalities into one core was to boost up their bioactivity potential. Furthermore, the variation in some part of final molecules was also processed in order to acquire new potent drug candidates. The pharmacological evaluation included enzyme inhibition, antioxidant activity and bovine serum albumin (BSA) binding analysis. The enzyme inhibition results were further substantiated through molecular docking analysis. The presented research work has been distributed into eight solid schemes for the synthesis of ninety six compounds. Ethyl isonipecotate (2) was treated with 4methoxybenzene sulfonyl chloride (1) in 5% sodium carbonate at pH of 9-10 to get ethyl-1-[(4-methoxyphenyl)sulfonyl]piperidine-4-carboxylate (3). Compound 3 and hydrazine monohydrate were refluxed in methanol to acquire 1-[(4methoxyphenyl)sulfonyl]piperidine-4-carbohydrazide (4). Compound 4 was refluxed with phenyl isothiocyanate in methanol to acquire an intermediate compound (2-({1[(4-methoxyphenyl)sulfonyl]-4-piperidinyl}carbonyl)-N-phenyl-1-hydrazinecarbothio amide) which was refluxed in basic medium to get 5-{1-[(4-methoxyphenyl)sulfonyl]4-piperidinyl}-4-phenyl-4H-1,2,4-triazole-3-thiol (5). Compound 5 was stirred with xiii different aralkyl halides (6a-j) in the presence of NaH and DMF using conventional and microwave assisted methods. 3-Aralkylthio-5-{1-[(4-methoxyphenyl)sulfonyl]-4piperidinyl}-4-phenyl-4H-1,2,4-triazole (7a-j) were obtained through filtration from aqueous medium. The compound 5 was treated with equimolar N-substituted-2bromoacetamides (10a-t) to acquire N-alkyl/aralkyl/aryl/phenyl-2-[(5-{1-[(4methoxyphenyl) sulfonyl]-4-piperidinyl}-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl] acetamide (11a-t). The electrophiles, 10a-t, were synthesized by the reaction of alkyl/aralkyl/aryl/phenyl amines (8a-t) and bromoacetyl bromide (9) in 5% sodium carbonate solution. The compound 5 was treated with equimolar N-substituted-2bromopropanamides (13a-r) to acquire N-alkyl/aralkyl/aryl/phenyl-2-[(5-{1-[(4methoxyphenyl) sulfonyl]-4-piperidinyl}-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl] propanamide (14a-r). The electrophiles, 13a-r, were synthesized by the reaction of alkyl/aralkyl/aryl/phenyl amines (8a-i, k, m-t) and 2-bromopropionyl bromide (12) in 5% sodium carbonate solution. Compound 4 was refluxed with methyl isothiocyanate in methanol to acquire an intermediate compound (2-({1-[(4-methoxyphenyl) sulfonyl]-4-piperidinyl}carbonyl)-N-methyl-1-hydrazinecarbothioamide) which was refluxed in basic medium to get 5-{1-[(4-methoxyphenyl)sulfonyl]-4-piperidinyl}-4methyl-4H-1,2,4-triazole-3-thiol (15). Compound 15 was stirred with different aralkyl halides (6a-j) in the presence of NaH and DMF using conventional and microwave assisted methods. 3-Aralkylthio-5-{1-[(4-methoxyphenyl)sulfonyl]-4-piperidinyl}-4methyl-4H-1,2,4-triazole (16a-j) were obtained through filtration from aqueous medium. The compound 15 was treated with equimolar N-substituted-2bromoacetamides (10a-t) to acquire N-alkyl/aralkyl/aryl/phenyl-2-[(5-{1-[(4methoxyphenyl) sulfonyl]-4-piperidinyl}-4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl] acetamide (17a-t). The compound 15 was treated with equimolar N-substituted-2bromopropanamides (13a-r) to acquire N-alkyl/aralkyl/aryl/phenyl-2-[(5-{1-[(4methoxyphenyl) sulfonyl]-4-piperidinyl}-4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl] propanamide (18a-r). The synthesized compounds were initially verified through TLC and stored for further analysis. The synthesized compounds were spectroscopically characterized by using IR, 1H-NMR, 13C-NMR, HMQC, HMBC, COSY, NOESY and EIMS spectral information to justify the available main functional groups, hydrogen atoms, carbon atoms and the fragmentation pattern of the structures of synthesized compounds. xiv The synthesized compounds were screened for enzyme inhibition activity against six different enzymes and also for antioxidant activity. The different six enzymes included acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), αglucosidase, urease, lipoxygenase and carbonic anhydrase II enzyme. Almost all the compounds were found to be excellent active agents against these enzymes. Antioxidant activityof all the synthesized molecules wasalso tested in search of some unique drug candidates. The chemistry of active sites and different functionalities responsible for the best pharmacological potential of all the synthesized compounds was verified through docking studies. In addition to it, the evaluation of protein drug interaction assisted us in understanding the various binding sites and binding constant to justify the stay of the drugs in the body, their circulation, metabolism, elimination and pharmacodynamics. The sketched compounds in the eight schemes were synthesized efficiently with high yield and purity through environment friendly protocol with minimum cost and time. The time of synthesis and the yield were compared for two modes of synthetic methods including conventional and microwave assisted ones. The following synthetic as well as biological screening studies resulted into the identification of a numberof compoundsbeing active against the considered enzymes. These enzymes are responsible for different kind of diseases and so the bioactive potent compounds may be considered as new drug candidates for the concerned diseases.