توریہ کے اصطلاحی مفاہیم اور اس کی شرعی حیثیت

Twriyah in a speech or word contains multiple meanings having different interpretations of its primary meaning. This article represents the linguistic and connotative concept of Twriyah and T’ryd in the light of Qur’an, hadith, Sirat, the views of various jurists. By analytical study of the available literature it is concluded that there is difference between using Twriyah and Falsification. There are several rules which regulate the use of Twriyah in special circumstances. All Messengers of Allah have never give false statements in any case, however they often used Twriyah in their statements. This article elaborated the various meanings and situations of Twryh in the light of Islamic teachings.

Anthraquinone Sulfonamides and Derived Heterocycles: Design, Synthesis, Biological Evaluation and Computational Studies

Leishmaniasis, a worldwide prevalent disease, is still enjoying the ruling with no proper medication; and to add to this current gloomy scenario the disease causing parasite Leishmania is becoming resistant to the ongoing medication that is being practiced now a days. Hence, the need is to search for reasonable, safe and targeted drugs; the present research is one such effort in this direction. To begin with, Leishmanolysin (GP63), zinc metalloprotease, expressed over the surface of Leishmania species was selected as drug target due to its virulence and reason for parasite resistance. A library of benzimidazole derivatives (1-37) was synthesized and screened for its antileishmanial potential against L. major. All the compounds were found potent antileishmanial with IC50 values in the range of 0.62-0.92 μg/mL as compared to amphotericin B (standard drug) IC50 value 0.56 μg/mL. 2-(Thiophen-2-yl)-1H- benzimidazole (19) and 2-(1H-indol-3-yl)-5-nitro-1H-benzimidazole (34) were identified as the lead compounds of the library with IC50 value of 0.62 μg/mL. ADMET properties of the entire library were also predicted by using ADMET PredictorTM and were observed to be safe. Molecular docking studies carried out on all the members of library and amphotericin B by using MOE software, indicated that the most active compounds fitted at the centre of binding pocket of GP63 built by amino acid residue His264, His268, His334 and Zn578. On the basis of molecular docking results, receptor based pharmacophore model was built containing three Aro|Hyd features and one Acc&ML feature. This pharmacophore model was used to design new scaffolds for antileishmanial compounds. Four libraries, 2-(2- aryl/heteroarylbenzimidazol-1-sulfonyl)anthraquinones (38-69), N-(heteroaryl)-anthraquinon-2- sulfonamides (70-95), aryl anthraquinon-2-sulfonates (96-111) and N-(anthraquinon-2-sulfonyl)-amino acid methylesters (112-123) were designed and all the cmpounds were found as hit by pharamocophoric search. Their antleishmanial activities were predicted by QSAR model; built by MOE software by selection of 94 descriptors and partial least square (PLS) method on experimental antileishmanial activity of 37-mebered library and amphotericin B, validated by internal and exernal test sets with correlation coefficient (R2) 0.7762. All the compounds belonging to four libraries (38-69, 70-95, 96-111 and 112- 123) were found potent antileihmanial with predicted activity in the range of 0.5435-0.9940. All the compouds were observed safe according to predicted ADMET properties and Lipinski’s rule of five (Ro5). Later, these four designed libraries were synthesized and characterized by physical constants and spectroscopic techniques for onward screening for their antileishmanial potential against L. major by using amphotericin B as standard control which confirmed that all the compounds were potent antileishmanial. Compliance of the predicted activity by QSAR model with observed activity from in vitro antileishmanial activity resulted in identification of the same lead compounds in each library 38-69, 70-95, 96-111 and 112-123 i.e. 2-(5-Nitro-4-methoxyphenyl-1H-benzimidazol-1-sulfonyl)anthraquinone (61) (predicted activity 0.6794, IC50 0.67 μg/mL), 2-(1H-benzo-1,2,3-triazol-1-sulfonyl)anthraquinone (91) (predicted activity 0.5579, IC50 0.57 μg/mL), 2-(1H-pyrazol-1-sulfonyl)anthraquinone (90) (predicted activity 0.5435, IC50 0.58 μg/mL), benzyl anthraquinon-2-sulfonate (100) (predicted activity 0.7615, IC50 0.76 μg/mL) and N-(anthraquinon-2-sulfonyl)-2-phenylglycine methylester (123) (predicted activity 0.7305, IC50 0.75 μg/mL). Pharmacophore based molecular docking studies carried out on all the eighty six compounds on GP63 by MOE software showed hydrophobic interactions, hydrogen bonding and metal ligation interactions with His268, His264, His334 and Zn578, respectively. This entire set of experiments in both dry and wet labs led to a successful designing of a variety of anthraquinon-2- sulfonamides as a novel scaffold having strong antileishmanial effect.