Defending Prophet’s Integrity in the Light of Shariah & Contemporary Work

Defending Prophet’s honor is religious and social duty of every Muslim, The Holy Prophet (r) being more valuable than our own lives and souls. The theme of love rests in its high correlation with obedience. That the one whom someone loves, his obedience and submission to him becomes easier, even to the extent of contentment and pleasure. Love of Allah and Holy Prophet (r) has been stressed upon in the article so that obedience of Allah and his Prophet and submission to them is expressed as easy and doable, and an instigation to avoid disobedience is generated. Success of a man lies in obedience of Allah and that of Holy Prophet (r). In this article, the facet of “Love” with Holy Prophet (r) has been comprehensively narrated. The prophet was deputed to be obeyed and followed to the dooms day unchecked of followers’ class, color or ethnicity. Such unconditioned following required his person to be of an extensively inclusive character, which it did, and that every single instant of his esteemed life is preserved. The most divinely of the services is moral building of nations on practical patterns. One way is of preaching, while even cultured is to assemble written material to be followed for long or elsewise forcefully bind people to follow ethical doctrines and avoid vice.

Computer-Guided Design and Synthesis of Il-2 Inhibitors As Immunomodulating Agents

Cytokine Interleukin-2 (IL-2) has a prevalent role in the growth, activation, and differentiation o f T-cells. To suppress immune responses associated with organ transplant rejection and other autoimmune diseases, it is important to disrupt the interaction of IL-2 with its receptor system. IL-2 is now emerging as a target in the discovery of novel therapeutics for addressing the problems related to immune system. The main goal of this study was to establish an effective in silico protocol for identification of IL-2 inhibitors. It describes a pharmacophore based virtual screening combined with docking study as a rational strategy for identification of novel IL-2 inhibitors. Structure based pharmacophore model was developed using the crystal structure of IL-2/IL-2Rα (PDB ID: 1Z92) complex. The predictive pharmacophore model consisted of three features, two hydrophobic and one cationic feature with three excluded volumes. The pharmacophore was validated using a training set of thirty known IL-2 inhibitors. Pharmacophore model as a 3D search query was searched against ZINC and MOE database, in order to retrieve new chemical scaffolds that may be potent IL-2 inhibitors. The hits retrieved from this search were filtered based on their RMSD values and pharmacophoric features. Hits that were retained were used in a molecular docking study to find the binding mode and molecular interactions with crucial residues at the active site of the target. Pharmacophore based molecular docking was carried out on virtually screened compounds using 1Z92 as target by MOE software that led to the identification of 15 hits belonging to diverse classes of heterocycles. These hits were further optimized and a library of forty six compounds including 5-6 membered azaheterocycles namely dihydropyrimidines, heteroazepines, pyrazoles and benzimidazoles besides some compounds such as chalcones and Schiff bases, was designed and synthesized. All newly synthesized compounds were characterized by their MS and NMR spectral analysis. IL-2 inhibition studies on the members of the synthesized library led to the identification of novel IL-2 inhibitors with IC 50 values ranging from <2- >50μg/ml using cyclosporine as a standard drug. This entire set of experiments in both dry and wet labs led to a successful designing and synthesis of a variety of compounds as novel scaffolds that may be developed into interesting immunomodulators.