معاصر خانقاہی نظام میں خانقاہ سراجیہ کے امتیازات

Mawlānā abu Sa'ad Ahmed Khan's sincerity, piety, adherence to the sunnah of the prophet and simplicity in his lifetime made this monastery a unique city in the subcontinent and a centre of universal growth and guidance. Gave after him Mawlānā Abdullah Ludhianvi, Khwaja Khan Muhammad and Khwaja Khalil Ahmad continued his mission. In addition to reforming the human population, the shuyūkh of this monastery has been following the sunnah of the prophet, reforming society, promoting education, preserving the belief at the end of prophethood, patronage of madrassas and religious parties, charitable work and promoting Naqshbandiyya.  And the emperors and officials have done their best to play their role in the implementation of the Islamic system and the establishment of the justice system in the country. Mashaikh of the monastery broke the intellectual statement of the religious schools by imparting practical training, Self-purification, spiritual asceticism, religious support, prophetic politics and modern insights. On the other hand, volunteer religious services and selfless sacrifice to bring the right path to the people, as well as the public meetings, strong character and perseverance religious influenced by source. Through his voluntary religious services and selfless sacrifices, he tried to bring them to the right… In this way, these gentlemen addressed the masses through Zikr, strong character and religious perseverance, influenced by source.

Study of Inhibition of Carbonic Anhydrase Ii and Dpp-Iv As Possible Targets of Drug Discovery

Research on enzyme inhibitors has an enormous potential to introduce new drug candidates against enzyme related diseases. Keeping this in view, present study was designed to identify natural and synthetic compounds as leads against two clinically important enzymes, carbonic anhydrase-II (CA-II) and dipeptidyl peptidase-IV (DPP-IV). Carbonic anhydrases (CAs), and dipeptidyl peptidase-IV (DPP-IV) have pathological roles in the emergence of number of diseases, particularly glaucoma and diabetes, respectively. The results of the study are summarized below: PART A CA-II is an important enzyme for many physiological processes. Inhibitors of CA-II are used for the treatment of many diseases, such as epilepsy, mountain sickness, and glaucoma. During this study, over 350 fully characterized compounds were evaluated against BCA-II enzyme. Out of which 58 compounds showed a good inhibitory activity. Among these compounds, bisindoles and thiourea derivatives of bisindolyl showed the most significant activity with IC50 values in the range of 14.4 – 70.36 μM. To study the mechanism of action of inhibitors, most active inhibitors of these classes were further subjected to kinetic studies. Inhibition constants and type of inhibition were deduced by using Lineweaver-Burk plot, secondary re-plot of Lineweaver-Burk plot, and Dixon plot. Inhibition type and dissociation constants were deduced by Lineweaver-Burk plot, secondary re-plot, and Dixon plot. Bisindole derivatives, such as 23 (N-(4-(bis(5-chloro-1H-indol-3-yl)methyl)phenyl)-2,4-dinitrobenzenesulfonamide), 28 (N-(4-(bis(5-chloro-1H-indol-3-yl)methyl)phenyl)-3,5-dichloro-2-hydroxybenzenesulfonamide), and 38 (N-(4- (bis(5-bromo-1H-indol-3-yl)methyl)phenyl)-2,4-dinitrobenzenesulfonamide) showed a significant inhibition of enzyme CA-II (IC50 = 15.6 – 28.86 μM). To assess their safety profile, cytotoxic studies were conducted on mouse fibroblast cell line (3T3). Fortunately some of the good active compounds were found non-cytotoxic, and thus can serve as leads for further studies on CA inhibitor drug design and development. PART B Epidemic prevalence of diabetes at national and global level emphasizes the need of urgent therapeutic intervention. In the second part of our work, we targeted an important enzyme of incretin pathway, dipeptidyl peptidase-IV (DPP-IV). Inhibitors of DPP-IV occupy center stage in the current anti-diabetic drug market. We screened over 1,800 fully characterized natural and synthetic compounds, through a mechanism-based colorimetric assay. This led to the identification of 87 new inhibitors. Significant inhibition was shown by the compounds of semicarbazones, thiosemicarbazone, benzophenone Schiff bases classes, and gold complexes. New inhibitors, identified through initial screening, were further subjected to mechanism-based kinetic studies. Lineweaver-Burk plot, secondary re-plot of Lineweaver-Burk plot, and Dixon plots were constructed to determine the type of inhibition, inhibition constant, and other kinetic parameters. Cytotoxic studies of active compounds were also conducted on mouse fibroblast cell line (3T3). Some potent inhibitors were also subjected to in situ DPP-IV inhibition assay by using Caco-2 cellular model. Synthetic compounds of different classes and Gold complexes were found to be active. Compounds (R)-2-phenyl-2,3-dihydrobenzo [d] imidazo[2,1-b] thiazole gold (I) triphenylphosphine tetrafluoro borate (204), (S)-2-phenyl-2,3-dihydrobenzo[d]imidazo [2,1-b]thiazole gold (I) triphenylphosphine tetrafluoro borate (207), and (S)-2-phenyl-2,3-dihydrobenzo[d] imidazo [2,1-b] thiazole gold (I) chloride (209) were identified as most potent inhibitors with IC50 values in the range of 22.0 – 35.6 μM. Earlier studies on DPP-IV inhibitors were restricted to selected number of compounds with limited structural variations. Present study presents comprehensive screening of different classes of synthetic compounds for the discovery of new inhibitors of DPP-IV. This is a cost effective, easy, reliable, and fast approach for the discovery of new drug candidates.