کتب علوم الحدیث میں امثال فقہیہ پر اختلاف مسالک کے اثرات؛ ایک تحقیقی جائزہ The effects of differences of Masalik on the Jurisprudential proverbs stated in the books of hadith studies

The foundation of the Sharia is revelation, revelation is the name of two things, the Qur'an and the Sunnah, since both are related to the news, and to convey the news to others, narrators are needed, so for the propagation of the Qur'an and the Sunnah to future generations. It was necessary to have narrators, the narrators of the Holy Qur'an are called Qira, the narrators of the Sunnah are called Muhaddith, the traditions of the Holy Qur'an are called 'Qara'at' and the traditions of the Sunnah are called 'Ahadith'. Both the Qur'an and the Sunnah are revelations, but still there are some differences between them which are explained in detail in the Book of Principles. It was a difficult task, and the significant efforts made by the Muhadditheen in this regard were more famous and campaigned than the knowledge of al-Qaraat and recitation. He became famous with this, and some people even got the wrong impression that he had nothing to do with jurisprudence, and this wrong impression was reinforced by the behavior of the some Narrators. In reasoning and deriving from the Sunnah, there were many disorders and factors that gave birth to different schools of jurisprudence. For example, a hadith revealed to an imam or a jurist during reasoning has a hidden reason that is not revealed to anyone else. Therefore, there is a difference in argumentation. Similarly, sometimes the hadeeth is correct in a certain issue in front of a jurist, while on the other hand, it is weak in the opinion of another, which leads to diversity in argumentation. When the jurists differed in the derivation of the issues and rulings, in fact, these are cases of priority and non-priority, in which there is, however, scope that any position can be declared preferred based on arguments. Keywords:               Hadith, Muhaddithin, Jurisprudential Proverbs, School of Thoughts, Differences.

Synthesis, Characterization Biological/ Photo Electrochemical Assay of Diverse Heterocyclic and Azo Scaffolds and Related Motifs

This research pertains to the synthesis, characterization and bio-evaluation of hybrids compounds in which two or more medicinally important nuclei are combine together in a single structural unit. Molecular docking studies were conducted to delineate the binding affinity of the molecules and a kinetic mechanism and mode of enzyme inhibition were proposed. The hybrids include thiazole-based coumarins arylideneamino thiazolyl ethanones, Azo-azomethines, Aza-thiosemicarbazones and sulfonamide-drug conjugates, In addition triazolo [1,2 a] [1,2,4]triazole-1,5-dithones, Thiazoliadinone, “6-substitued triazolo thiadiazoles, pyrazoles, thiazolo [3,2-b]-[a1,2,4]-triazoles, were also prepared . An efficient synthesis of thiazolo-coumarin derivatives; (213-222) was accomplished in three steps from suitable reactants. UV Visible spectra of the compounds were carried out in different solvents DMF, ethanol, methanol, ethyl acetate and acetone and the absorption was observed in the range 338-390 nm. Electrochemical study of thiazoles was conducted in DMF and redox behavior was also examined. Fluorescence carried out in ethanol showed sharp emission in the range 440-505 nm. Another one-pot synthesis of coumarinyl appended thiazoles was achieved by the reaction of 3-bromoacetylcoumarin with separately prepared thiosemicarbazones.The synthesized molecules were investigated for the inhibition activity against human tissue-nonspecific alkaline phosphatase and human intestinal alkaline phosphatase. Most of the tested compounds exhibited the selective and potent inhibition profile towards isozyme. However, few derivatives showed inhibition of both the enzymes. Molecular docking studies were conducted to explore the binding interactions and modes of potent compounds. Arylidene aminothiazolyl ethanones (236-243) were obtained by reacting 3-cholor0acetyl acetone with urea then reaction with benzaldehydes. Biological evaluation as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was carried out. Almost all compounds were selective inhibitors of AChE with (236) most potent AChE inhibitor (IC50±), Kinetics and molecular docking studies of most potent inhibitors were carried out. Additionally naked-eye coloured chemodosimeteric probes (244-249), based on Schiff-azo dye conjugates were prepared and characterized. The compounds (244-249), exhibited excellent selectivity and high sensitivity in absorbance toward detection of Fe(III) in alcoholic solutions under neutral pH conditions. The detection limit of the probe was shown to be up to 0.05 ppm and fast watching of Fe(III) method was also established. Electrochemical analysis of metal-free conjugates and iron chelated probes confirmed the chelation of ligands. A novel series of carbothioamides was prepared (250-265) by the reaction of thiosemicarbazide with the aldehyde, and tested for urease inhibitory activity Compound (255), bearing furan was the most potent inhibitor IC50 =0.58 lM. Molecular modelling revealed them to have similar binding style to the urease inhibitors. Fused triazolo-dithiones were obtained by reaction of thiosemicarbazide with aliphatic aldehydes in good to excellent yields and two successive intramolecular hetero-cyclizations mechanism was suggested. Synthesis and enzyme inhibitory kinetics of methyl [2-(arylmethylenehydrazono)-4-oxo-thiazolidin-5-ylidene] acetates (278-287) as mushroom tyrosinase inhibitors. The compounds were synthesized via cyclocondensation of thiosemicarbazones (278-287) with dimethyl but-2-ynedioate (DMAD) in good yields under solvent-free conditions. The synthesized compounds were evaluated for their potential to inhibit the activity of mushroom tyrosinase. It was unveiled that compounds (286) indicated excellent enzyme inhibitory activity with 3.17 mM while IC50 of standard kojic acid is 15.91 mM. The presence of heterocyclic pyridine ring in compound (286) play important role in enzyme inhibitory activity as rest of the functional groups are common in all prepared compounds. New thiadiazole derivatives (304-318) was achieved by phosphine free, C–H arylative cross-coupling of (289-303) with iodoanilines using an acyl thiourea as a ligand. Another small series of new 3,5-Dimethyl-4-(arylsulfanyl) pyrazoles obtained by a grinding-induced, sequential three-component reaction, of an equimolar mixture of 3-Chloro-2,4-pentanedione, differently substituted thiophenols, and hydrazine hydrate in the presence of piperidine under solvent-free conditions. Aryl pyrazoles are the well-recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in New aryl pyrazoles were prepared by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound (333) (IC50 =1.568 ± 0.01μM) showed relatively better potential compared to reference kojic acid (IC50 =16.051 ± 1.27 μM). Ten fused heterocyclic derivatives bearing the 2,6-Di(substituted phenyl)thiazolo-triazoles as central rings were synthesized. In vitro inhibitory activities of synthesized compounds on α-amylase, α-glucosidase and α-burylcholinesterase (α-BuChE) were evaluated using purified enzyme assays. Compound (342) demonstrated strong and selective α-amylase inhibitory activity (IC50 = 1.1 mmol/g). The compound (346) exhibited excellent inhibition against α-glucosidase (IC50 = 1.2 mmol/g) when compared with acarbose (IC50 = 4.7 mmol/g) as a positive reference. Compound (348) was found to be most potent derivative against α-BuChE with the IC50 of 1.5 mmol/g which was comparable to the (4.7 mmol/g) positive control (galantamine hydrobromide). Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also evaluated. All the 24 synthesized compounds exhibited excellent potential for urease enzyme. Compound (354) (IC50 = 0.081±0.003 μM), 356 ( IC50 = 0.0022 ±0.0002 μM), 366 ( IC50 = 0.0250 ±0.0007 μM) and 371 ( IC50 = 0.0266±0.0021 μM) were found to be the lead compounds compared to standard (thiourea, IC50= 17.814).