مشکوٰۃ المصابیح پر شیخ عبدالحق محدث دہلوی کے کام کا جائزہ

"Mishkāt al-Maṣābīḥ" has a sound rank among the Hadith collections. Its importance can be gauged from the fact that it has been described and summarized by several scholars. The works of Sheikh Abdul Haq Muḥaddith Dehlavi over that is a great contribution and have a special place in the context of his Hadith services. He is one of the prominent muhaddithin of the Subcontinent. He was pioneer in teaching and disseminating Hadith knowledge in the subcontinent. Firstly, he described the Mishkāt al-Maṣābīḥ in the Persian language of that time, which gained immense popularity among the people and increased the taste for understanding Hadith. Secondly, He accumulated a treasure trove of mysteries and secrets in Arabic for the use of Researchers. The name of the Persian commentary is Ash‘atul Lam‘āt while the Arabic commentary is called Lam‘āt al-Tanqīh. They are more than one in usefulness, which has created a taste for reading and understanding Hadith among the people and Researchers. In the said article, an introduction and methodological study of the work done by Sheikh Abdul Haq on Mishkāt al-Maṣābīḥ will be presented.

Synthesis and Characterization of Potentially Biologically Active Compunds Derived from Fibric Acids.

The present study deals with the synthesis of fibric acids derivatives. The thesis has been divided into three parts (1) Synthesis of fibric acids derivatives (2) Biological screening (3) In silicio studies. In the first part of thesis two fibric acids (2a & 2b) were synthesized from two phenols (1a & 1b) followed by their conversion into corresponding esters (3a & 3b) and carbohydrazides (4a & 4b). Cyclization of these carbohydrazides was carried out to synthesize 1,3,4-oxadiazoles (5a & 5b). In next step N-substituted-2-bromoacetamides (7a- 7y) were prepared by using various anilines (6a-6y). Two main series of compounds 8-30 and 31-50 were synthesized successfully by reacting 5-(2-aryloxypropan-2-yl)-1.3.4- oxadiazol-2-thiols (5a & 5b) with N-substituted-2-bromoacetamides (7a-7y). Characterization of the compounds was carried out through spectroscopic analysis. N N O CH3 CH3 O X SH (5a-5b) 5a X=Cl 5b X=Br (Scheme 1) xiv Br N H O R1 R2 (7a-7y) 7a Cyclohexylamine 7j R1 = 3CH3 R2=5CH3 7s R1 = H R2=2Br 7b R1 = H R2=H 7k R1 = H R2=4C2H5 7t R1 = H R2=3Br 7c R1 = H R2=2CH3 7l R1 =2C2H5 R2=6CH3 7u R1 = H R2=4Br 7d R1 = H R2=3CH3 7m R1 = H R2=2OCH3 7v R1 = H R2=2Cl 7e R1 = H R2=4CH3 7n R1 = H R2=3OCH3 7w R1 = H R2=4F 7f R1 = 2CH3 R2=3CH3 70 R1 = H R2=4OCH3 7x R1 = H R2=4NO2 7g R1 = 2CH3 R2=4CH3 7p R1 = H R2=2OC2H5 7y R1 = H R2=2NH2 7h R1 = 2CH3 R2=6CH3 7q R1 = H R2=4OC2H5 7i R1 = 3CH3 R2=4CH3 7r R1 = 2OCH3 R2=5Cl (Scheme 2) N N O CH3 CH3 O Cl S N O H R1 R2 (8-30) 8 Cyclohexylamine 16 R1 = 3CH3 R2=4CH3 24 R1 = 2OCH3 R2=5Cl 9 R1 = H R2=H 17 R1 = 3CH3 R2=5CH3 25 R1 = H R2=2Br 10 R1 = H R2=2CH3 18 R1 = H R2=4C2H5 26 R1 = H R2=4Br 11 R1 = H R2=3CH3 19 R1 =2C2H5 R2=6CH3 27 R1 = H R2=2Cl 12 R1 = H R2=4CH3 20 R1 = H R2=2OCH3 28 R1 = H R2=4F xv 13 R1 = 2CH3 R2=3CH3 21 R1 = H R2=4OCH3 29 R1 = H R2=4NO2 14 R1 = 2CH3 R2=4CH3 22 R1 = H R2=2OC2H5 30 R1 = H R2=2NH2 15 R1 = 2CH3 R2=6CH3 23 R1 = H R2=4OC2H5 (Scheme 3) N N O CH3 CH3 O Br S N O H R1 R2 (31-50) 31 Cyclohexylamine 38 R1 = 2CH3 R2=6CH3 45 R1 = H R2=2OC2H5 32 R1 = H R2=H 39 R1 = 3CH3 R2=4CH3 46 R1 = H R2=4OC2H5 33 R1 = H R2=2CH3 40 R1 = 3CH3 R2=5CH3 47 R1 = 2OCH3 R2=5Cl 34 R1 = H R2=3CH3 41 R1 = H R2=4C2H5 48 R1 = H R2=2Br 35 R1 = H R2=4CH3 42 R1 =2C2H5 R2=6CH3 49 R1 = H R2=3Br 36 R1 = 2CH3 R2=3CH3 43 R1 = H R2=3OCH3 50 R1 = H R2=4Br 37 R1 = 2CH3 R2=4CH3 44 R1 = H R2=4OCH3 (Scheme 4) After the successful completion of synthetic portion and their characterization fibric acids derivatives were evaluated for their biological activities. For this purpose, protocols of anti-thrombotic (in vitro and in vivo) and anti-inflammatory activity (in vitro and in vivo) were followed. The anti-thrombotic activity (in vitro and in vivo) was performed to evaluate the FXa inhibition potential of newly synthesized compounds. In vitro, compounds 17, 27 and 36 showed higher % age of clot lysis than standard drug streptokinase; however the xvi remaining compounds showed moderate to good activities. In vivo, for compounds 9, 12, 13, 16, 17, 24, 27, 32, 36, 39, 41, and 48 enhanced clotting times (even better than standard drug heparin) were observed. Anti-inflammatory activity was performed to evaluate the COX-2 enzyme inhibition potential of fibric acids derivatives. In vitro, these compounds showed moderate to good activity while in vivo compounds 8, 9, 11, 12, 16, 17, 24, 34 and 48 showed results even better than standard drug diclofenic sodium. Compounds 14, 15, 19, 21, 31, 38 and 42 results were comparable to that of standard drug while remaining compounds exhibited moderate activity. In the last part of research work in silico studies were performed for selected compounds. For anti-thrombotic activity compounds 9-17 were docked against FXa protein. Except the compound 5a, all others showed higher docking score than the control ligand. In case of anti-inflammatory activity molecular docking of compounds 5a, 5b and 8-50 was carried out against COX-2 protein. All the compounds except 5a, 5b, 13 and 25 showed higher docking score than standard. Density functional theory (DFT) computed molecular properties of compounds 9-17 were also calculated by computational methodology. Results of biological activities showed good commitment with in silico study results. In future these compounds might be evaluated at molecular level.