لانبہ ، سردار نرنجن سنگھ
انتقال پر ملال
حضرت مفتی عتیق الرحمن عثمانی ؒ کے انتہائی عقیدت مند سردار نرنجن سنگھ لانبہ ۴ جنوری ۱۹۹۳ء کی علی الصبح کو اچانک انتقال فرماگئے۔ وہ ۸۴ سال کے تھے۔ اور بڑے ہی مخلص اور غریبوں کے ہمدرد و بہی خواہ تھے۔ بہت بڑے کاروباری ہوتے ہوئے بھی بے سہاروں، بیواؤں، یتیموں کی فلاح و بہبودگی کے کاموں میں بڑھ چڑھ کر حصہ لیتے تھے، انسانیت کی خدمت میں ہمیشہ جٹے رہتے تھے۔
مفتی عتیق الرحمن عثمانی کے جاں نثار و فدا ئی تھے، ان سے تعلق ِخصوصی قیام پاکستان سے قبل راولپنڈی ہی سے تھا، برابر خط و کتابت رہتی تھی۔ قیام پاکستان کے بعد مفتی صاحب کی عقیدت و محبت ہی انہیں دہلی کھینچ لائی تھی۔ تعصبات و تنگ نظری سے بالکل پاک و صاف تھے، بلا لحاظ مذہب و ملّت ضرورت مندوں کی امداد کرتے رہتے تھے۔ حضرت مفتی عتیق الرحمن عثمانی کے انتقال کی خبر ملتے ہی بلک بلک کر رونے لگے اور کہنے لگے کہ آج ہمارے مسلمانانِ ہند اور ملک کے اوپر سے سایہ ٔ شفقت اٹھ گیا ہے۔ مفتی صاحب کے جنازے میں باوجود سخت بیماری و تکلیف کے جامع مسجد سے مہندیان تک پیدل ہی چلتے رہے، لوگوں نے ان کے درد کی شدت کو محسوس کرتے ہوئے انھیں سواری میں بیٹھنے کے لیے کہا تو بولے کہ جس ہستی نے ملک و قوم کی خدمت میں اپنی پوری زندگی قربان کردی اس ہستی کے لیے ہم پیدل بھی نہیں چل سکتے کیا؟
حقیقت تو یہ ہے کہ لانبہ صاحب قدیم روایات و تہذیب کے امین تھے۔ ان کے انتقال سے ایک خلا سا محسوس ہورہا ہے ۔ حق تعالیٰ سے دعاہے کہ ان کے انتقال پر ملال پر ہم سب کو، ان کے متعلقین کو اور ان کے تمام...
Those who abused the Prophet r, and accused him of violence, slander and falsely, had never listened to the call of the mind. They should never ignore the one of the most important verses of the holy book revealed from the Creator, Allah Almighty, that Prophet Muhammad r has been sent to the mankind purely for offering mercy. How can they neglect the fact that the Prophet r himself said if he was a leader without mercy, people around him did not accompany him. When we study the life of Prophet r, we observe that all factions of the society, whether they are slaves or independent, Muslims or non- Muslims, men or women, beloved friends or worst enemies; they were behaved not only with extreme justice, but with utmost mercy. So we find that it was a mercy in everything, in education, in advocacy and in legislation, in war and peace, in the family and society, and in all walks of life, etc. In this article, aspect of mercy in the personality of holy Prophet Muhammad r has been discussed in detail. Opinions of the Orientalists are also presented in the article. Aspect of mercy was not only an ingredient of the personality of Prophet r, but He r also made mercy a part of his followers’ personalities. So history witnesses that there was an elongated reign of peace in the world, whenever Muslim Rulers were in power.
Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine kinases with three structurally homologous mammalian isoforms, Akt1 (PKBα), Akt2 (PKBβ), and Akt3 (PKBγ). Akt isoforms emerged as anti-cancer drug targets because of their constitutive hyperactivation in various oncological disorders. However, due to high intra-family similarity within ATP binding region, the development of isoform-selective modulators of Akt represent a challenging endeavor and thus, until now only a handful of compounds were selected for the clinical investigation. Yet none of them could reach the market for routine clinical use due to their off-target toxicity and poor pharmacokinetic properties. Recent reports on achieving isoform selectivity by designing inhibitors against less conserved pleckstrin homology (PH) domain offer the opportunity to reduce the major off-target toxic effects of Akt antagonists. Therefore, in this thesis, combined ligand- and structure-based in silico strategies have been utilized to probe the key structural features for the inhibition of the PH domain of Akt2 which is more commonly overexpressed in solid tumors. Toward this end, various predictive 2DQSAR (two-dimensional quantitative structure-activity relationship) and GridIndependent Molecular Descriptor (GRIND) and pharmacophore models using structurally diverse data set of 111 quinoline analogs have been developed. Our key findings demonstrate that the presence of three hydrogen bond donors (D1-D3) at a molecular distance of ~8.4, 21.6, 16.8 Å between D1–D2, D1–D3 and D2–D3, respectively is important for selective inhibition of PH domain of Akt2. In addition, our docking results indicated a crucial role of Lys30 for the optimal fit of quinoline-type inhibitors within the binding cavity of the Akt2 PH domain. Moreover, the structurebased pharmacophore model exhibited three hydrogen bond acceptors (A1-A3) at a distance of 4.05 Å (A1-A2), 11.58 Å (A2-A3) and 15.33 Å (A1-A3) that are complementary to the molecular distances identified by GRIND which further validate the reliability of our developed models. Additionally, identified hits through pharmacophoric-based virtual screening provided a new arsenal of potentially selective chemical scaffolds which have a broad structural diversity and less chemical similarity to any of the other known Akt2-PH domain inhibitors. Subsequently, selectivity profiling with the help of proteochemometric modeling revealed essential substructures such as Nmethylpent-3-en-2-amine for selective inhibition of Akt1, methylene amine, isoproenylterazol and 2H-tetrazole for Akt2, and formaldehyde hydrazine for the Akt3 selective inhibition. The present work also illustrates the substructure based similarity search of ChemBridge database to identify Akt2-selective hit compounds. In the present study, one of the selected carboxamide-type hit showed 1.2 and 2.1 fold selectivity against Akt2 as compared to Akt1 and Akt3, respectively. Overall, the work described in this thesis could pave the way towards the identification of potential modulators of Akt2 against cell proliferation in cancer with high isoform-selectivity and limited side effects.