صوفیہ خام اور علمائے سوء کا علمی محاسبہ کشف المحجوب کی روشنی میں

This paper is an attempt to elaborate and highlight the attributes and qualities of leading specialists and reformative factors of Islamic society blessed with moral par-excellence known asṢūfiyā and‘Ulamā’. As unfortunately, with an exception of few, these responsible characters have gone astray following ill commanding self like a wolf in sheep’s dress hiding their harmful aspects with friendly appearance. These so-called knowledge spreading elements and spiritual mentors are also accountable to disparage the values and thought associated with Islamic system of learning and self-purification. So, it is necessary to remove the curtain in order to visit the real picture of Taṣawwaf. For this purpose, a book ‘Kashf al-Maḥjūb’ of great Sufi scholar Syed Alī bin ‘Uthmān al Hujvairī (R.A)has been selected to examine analytically how he discussed the situation in the light of Qur’ān and Sunnah elaborating the misconduct and bad behavior of under discussed. One who disguised himself instead of having conflict between his internality (self) to that of externality. The habits and attitude of imperfect Ṣūfiyā and the misleading ‘Ulamā’ and their injurious impact on society have been discussed by Alī Hujvairī (R.A) in his comprehensive treatise. The author also setout a strategy to know how to get rid of these so-called Ṣūfiyā and‘Ulamā’ and suggested various outlines and framework for recuperation in order to save the humanity from their lethal side effects.

Synthesis, Identification, Biological Investigation and Molecular Docking Studies of Aromatic/Heterocyclic Derivatives As Monoamine Oxidase Inhibitors

Monoamine oxidase inhibition offers potential therapeutic target for the management of depression and Parkinson’s disease. Keeping this in view, the present study was designed to select and synthesize potential scaffolds followed by monoamine oxidase inhibition, computational studies, behavioral and neurochemical assessments. Five different types of scaffolds (pyrazolobenzothiazine-based carbothioamides, chromones, chalcones and quinoline carboxylic acid derivatives) and a synthetic compound oxatomide were selected for this study based on their potential to interact therapeutically with MAO enzyme. Their various derivatives were synthesized and structurally characterized using spectroscopic methods i.e., mass and NMR. All compounds were subjected to monoamine oxidase A and B inhibition assay using the kynuramine or the amplex red method. The data showed that pyrazolobenzothiazinebased carbothioamides held significant potential to inhibit both MAO-A and B. Compounds 2-(4-(3,4-dimethyl-5,5-dioxidobenzo pyrazolo[4,3-c][1,2]thiazin-2(4H)yl) benzylidene)-N-(p-tolyl) hydrazine carbothioamide (3b) (IC50 = 0.003 ± 0.0007 mM) and N-(4-ethylphenyl)-2-(4-(4-methyl-5,5-dioxido-3-phenylbenzo pyrazolo[4,3c][1,2]thiazin-2(4H)-yl) benzylidene) hydrazine carbothioamide (4d) (IC50 = 0.02 ± 0.001 mM) inhibited the enzyme with efficacy comparable to that of the standard inhibitors, clorgyline and deprenyl. Computational docking studies revealed that 3b showed interaction to Tyr407 and Tyr444 pi-interactions from 4-methylphemyl zone of molecule, and the bezothiazine ring was oriented to hydrophobic pocket of the active site. The amino acids Ile325, Ile335, Phe352, Tyr69 and Tyr197 showed Van der Waals interactions while amino acids Tyr407, Gln215, Val210, Phe208, Ile180, and Cys323 showed polar interaction to flavin adenine dinucleotide (FAD). Kinetic data revealed compound 3b as a noncompetitive inhibitor. Phenothazine ring of 4d showed pi-stacked-interactions to Tyr398 and Tyr435. Ethylphenyl-side was oriented to entrance cavity. Van der Waals interactions were found with Phe103, Leu164, Phe168, Ile199, Tyr326 and Phe34. Apart from π-π interactions with the Tyr398 and Tyr435, FAD and other residues such as Gln206 and Ile316 showed polar interactions with 4d. Thus aryl substitution was necessary for the observed function of these molecules. Enzyme kinetics showed 4d to be a competitive inhibitor for MAO-B. These compounds were tested for their efficacy in-vivo. The compound 3b caused significant decline in the immobility time in tail suspension test, while compound 4d significantly reversed the effect of rotenone as suggested by the remarkable increase in time spent on Rotarod. Hence, it can be deduced that both of this compounds have the ability to reach CNS to produce their desired effects. Their effects were further confirmed by neurotransmitter analysis. The brains from 3b treated animals showed significant increase in the levels of norepinephrine and serotonin alone with decline of its metabolite i.e., 5-hydroxyindoleacetic acid. However, the 4d treatment caused significant increase in dopamine levels with corresponding decline in its metabolites i.e., 3,4 dihydroxyphenylacetic acid and homovanilic acid. The aforementioned analysis is suggestive of preferential effect of 3b and 4d on MAO A and B, respectively in vivo. Hence, both of these compounds are suitable candidates for the development of MAO inhibition based therapy for the management of depression and Parkinson’s disease.