ولادت النبیﷺ سے متعلق سیرۃ کی چند روایات کا تحقیقی جائزہ

Allah sent Hadrat Muhammad (SAW) as last Prophet and preserved his all aspect of life for the complete guidance of mankind. Love with the Holy Prophet (SAW) is a part of the Faith. But it has become the standard of his love that all the things which are attributed to him either authentic or unauthentic are accepted without research. Regarding the S╚rah (life) of Holy Prophet (SAW) numerous authentic narrations are exist, but on the other hand some fabricated narrations also mentioned by the story-teller historians, so be careful while propagating these narrations. Some narrations are very famous regarding the birth of the Holy prophet (SAW) which are far away from the reality. In this article some narrations regarding the birth of the Holy prophet (SAW) are scholarly reviewed in the light of the views of the scholars of Jarh-o- Ta‘d┘l in order to find their legal status.

Synthesis, Characterization and Biological Evaluation of New Analogues of Penicillin Group of Antibiotics

The work presented in this thesis consists of synthesis, characterization and biological screening of penicillin analogues. This work also describes the optimisation of a lead inhibitor of metallo-β-lactamases previously identified by fragment screening of a compound library. Keeping in view the wide spread of resistant strains of microorganisms there is an urgent need for the development of new antibacterial agents to treat the patients infected with multidrug resistant bacteria, we select 6-aminopenicillinic acid (6-APA) as a precursor for the synthesis of new penicillin analogues. These penicillin conjugates were prepared by acylation of 6-APA with different acid chlorides in aqueous medium. A number of 4-substituted benzoic acids were required for this work. Different substituted 4-benzoylbenzoic acids were prepared form the appropriate substituted benzoic acids by regioselective Friedel-Crafts acylation of toluene promoted by phosphorus pentoxide adsorbed onto silica, followed by benzylic oxidation using Jones reagent in hot acetic acid. Starting with 4-benzoylbenzoic acid, hydrogenolysis gave 4-benzylbenzoic acid, while partial reduction with sodium borohydride gave the benzylic alcohol-acid. 3-(4-Methylbenzoyl)benzoic acid used in this work was prepared by the hydrolysis of dimethyl isophthalate to the monoacid which was then subjected to the Friedel-Crafts acylation with toluene and phosphorus pentoxide on silica gel to yield the methyl 3-(4-methylbenzoyl)benzoate. Finally, saponification of methyl 3-(4-methylbenzoyl)benzoate gave the required carboxylic acid. The monoacid ester of isophthalic acid was treated with pivalyl chloride and triethyl amine in dichloromethane which was then condensed with piperidine and pyrrolodin to get methyl 3-(piperidine-1-carbonyl)benzoate and methyl 3-(pyrrolodin- 1-carbonyl)benzoate respectively. The saponification of these two esters was accomplished with LiOH.H2O in 30 % water methanol solution to give their respective carboxylic acids. The final carboxylic acids used in this work were synthesized by acetylation of 4-hydroxybenzoic acid and 2-hydroxybenzoic acid. Finally all these carboxylic acids were then converted to their respective acid chlorides for the acylation of 6-APA. These penicillin analogues were then screened against Gram-positive and Gram-negative bacterial strains for their antibacterial activity. These compounds were also screened against IMP-1 metallo-β-lactamase. Briefly, kinetic studies were performed using the chromogenic substrate CENTA and a 96-well plate reader at pH 7.00 and monitoring the development of the chromophore 4-nitrothiophenolate at 405 nm. We screened these penicillin conjugates too against fully reduced pig purple acid phosphatase (pPAP) using 5 mM PNPP as a substrate at pH 4.9 with reduction time 132-264 sec. In this study we found out new biological activity associated with this class of compounds. During preliminary biological screening it was found that penicillin conjugates had significant inhibitory activity against pig PAP with Ki values as low as 12 μM. The interactions of the most potent inhibitors and the active site of imipenemase (IMP-1), pig purple acid phosphatese (pPAP), and human purple acid phosphatese (hPAP) were examined using in silico docking methods. For the optimisation of a lead inhibitor of metallo-β-lactamases, 1,2,4- Triazole-3-thiols were prepared in most cases from acylated thiosemicarbazides on treatment with strong base, either aqueous sodium hydroxide solution or sodium ethoxide in ethanol. Acylated thiosemicarbazides were prepared by a variety of methods, either direct thermal condensation of thiosemicarbazide with carboxylic acids or by acylation of thiosemicarbazide with acid chlorides or acid anhydrides. In some cases the intermediate acylated thiosemicarbazides could not be isolated, and the 1,2,4-triazole-3-thiol products instead formed directly. A fortuitous discovery was that many of the acylated thiosemicarbazide synthetic precursors of the triazole-thiols did themselves possess high potencies against the IMP-1 MBL with Ki values as low as 11 μM, comparable with the potency of already reported inhibitor captopril (Ki = 12.5 μM).