مولانا آزاد سجانی
دوسرا حادثہ مولانا آزاد سبحانی کی وفات کا ہے، نئی پود کو کیا معلوم کہ ایک زمانہ میں مولانا کتنی بڑی شخصیت رکھتے تھے، اگر ان کے دل و دماغ میں توازن اور خیالات و عمل میں استقلال ہوتا تو ہندوستان کے چوٹی کے علماء اور لیڈروں میں ان کا شمار ہوتا، وہ بڑے ذہین اور وسیع النظر عالم معقولات کے ماہر اور سحربیان خطیب تھے، ان کی تقریر خطابت اور منطق کا مرقع ہوتی تھی، ایک زمانہ میں مدرسہ الٰہیات کانپور کے روح رواں اور مسجد کانپور کے واقعہ کے ہیرو تھے، ہندوستان کی جنگ آزادی میں بھی ان کا حصہ ہے تحریک ترک موالات میں اور اس کے بعد بھی کچھ دنوں تک گاندھی جی کے رفیق کار اور کانگریس کے سرگرم رکن رہے، مگر ان میں استقلال نہ تھا، کسی مسلک پر زیادہ دنوں تک قائم نہ رہتے تھے اور عجیب عجیب تحریکیں اختراع کرتے تھے، ادھر کئی سال سے اسلامی کمیونزم اور حکومت ربانی کے مبلغ بن گئے تھے اور اس پر ایک کتاب بھی لکھی تھی، مگر کسی تحریک کو عرصہ تک نہ چلا سکے اور سب کا خاتمہ ناکامی پر ہوا، ادھر عرصہ سے سب جماعتوں سے الگ ہوگئے تھے اور ان کی زندگی کا آخری دور گمنانی میں بسر ہوا، مگر اس حال میں بھی جب کہ بڑی شکستہ حالت میں حکومت ربانی کی تبلیغ کرتے پھرتے تھے جب کسی مسئلہ پر گفتگو کرتے تھے تو معلوم ہوتا تھا کہ کوئی بڑا مفکر اور فلسفی بول رہا ہے، ان کی خاموش موت دنیاوی شہرت کی بے ثباتی کا سبق آموز واقعہ ہے ایک زمانہ میں جس کی خطابت کی سارے ہندوستان میں دھوم تھی، اس کی موت کو اخبارات نے ایک معمولی واقعہ سے زیادہ اہمیت نہ دی اور بہتوں کو اس کی خبر بھی نہ ہونے...
Until recently, Gwadar has always been mentioned as a small insignificant fishing town. Very little was known about its history and potential to the outside world. However, at the turn of the 21st century Gwadar became the focus of attention globally. The development of a deep seaport with China’s assistance and prospects of connecting China and Central Asia through Pakistan to the North Arabian Sea has brought this small, insignificant fishing town to international recognition. But history reveals that this region has always played a vital role since primeval times due to its geostrategic and geographical location. From Alexander’s retreat to Pakistan’s reclaiming Gwadar, it has always reminded its significance at different times in diverse manners. This paper aims to bring into light the historical journey of Gwadar, which usually remained unknown or were either considered trivial by historians. Gwadar became an important chapter in the Belt and Road initiative proposed by the Chinese president. It will link China, South Asia, Middle East, Central Asia, Africa and Europe through a network of land and sea routes and ports will contribute significantly to the progress and prosperity of Gwadar in Pakistan, China and the entire region.
The Chemistry and biological studies of heterocyclic compounds has been important field for a long time in Medicinal Chemistry. It is a fundamental need for the development of new drugs having potent activities. The discovery of new drug candidates has been the burning issue of all the times owing to new emerging diseases. Synthetic and natural heterocyclic compounds are the subject of R & D units of many pharmacological, agrochemical and industrial laboratories. Around 90% of new medications contain heterocyclic moieties. The presented work is a contribution in the field of pharmaceutical industry regarding the discovery of new drug candidates. The amalgamation of two heterocyclic moieties i.e. 1,3-thiazole and 1,3,4-oxadiazole, were carried out in the designed molecules to impart them possible therapeutic properties. The new compounds have been synthesized by encompassing different bioactive moieties including 1,3-thiazole, 1,3,4-oxadiazole, alkyl halide, Acetamide and propanamide. The synthesized molecules have been subjected to evaluation of their antibacterial, enzyme inhibitionand hemolytic potential. Furthermore, enzyme inhibition potential results have been supported by computational docking in order to find the types of interactions with the active site of involved enzymes. Six (06) schemes have been used to demonstrate the synthesis of ninety (90) compounds. In Scheme-1, 1,3-thiazole-2-amine (1) wasstirred with 2-bromoacetyl bromide (2) in basic medium to yieldN-(1,3-thiazol-2-yl)-2-bromoacetamide (3) as an electrophiles. In a parallel reaction different 5-substituted-1,3,4-oxadiazol (7a-o) were synthesized from corresponding aryl carboxylic acids (4a-o) through esterification and hydrazide formation. The final compounds, 8a-o, were synthesized by stirring 7a-o and 3 in an aprotic polar solvent. In Scheme-2, the synthesis was initiated by the reaction of 4-methyl-1,3-thiazol-2-amine (9) with bromoacetyl bromide (2) in aqueous basic medium to obtain an electrophile,2-bromo-N-(4-methyl-1,3-thiazol-2-yl)acetamide (10). In parallel reactions, a series of carboxylic acids, 4a-o, was converted, through a sequence of three steps, into respective 1,3,4-oxadiazole heterocyclic cores, 7a-o, to utilize as nucleophiles. Finally, a series of compound, 11a-o, was synthesized by coupling 7a-o, individually, with 10 in an aprotic polar solvent. In Scheme-3, firstly, an electrophile, 2-bromo-N- XII (5-methyl-1,3-thiazol-2-yl)acetamide (13), was synthesized by the reaction of 5-methyl-1,3-thiazol-2-amine (12) and bromoacetyl bromide (2) in an aqueous medium. Then, the electrophile 13 was coupled with the aforementioned1,3,4-oxadiazoles (7a-o)to obtain the targeted bi-heterocycles (14a-o). In Scheme-4, the synthesis was initiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (15) to corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (16) by the reaction with hydrazine hydrate in methanol. The treatment of acid hydrazide, 16, with carbon disulfide gave a bi-heterocyclic 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol (17). The target compounds, 19a-o, were synthesized by stirring the parent 17 with different electrophiles, 18a-o, in DMF using LiH as weak base and activator. In Scheme-5, the synthesis of a new series of S-substituted derivatives, 23a-o, of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (17) were synthesized and evaluated for enzyme inhibition study along with cytotoxic behavior. Different electrophiles, 22a-o, was synthesized by the reaction of aniline (20a-o) and 2-bromoacetyl bromide (21) in an aqueous medium. The target compounds were synthesized by stirring 17 with different electrophiles, 22a-o, in DMF using LiH as weak base and activator.In Scheme-6, the synthesis of a novel series of bi-heterocycles, 26a-o, was accomplished by S-substitution of 5-(2-amino-1,3-thiazol-4-yl)methyl)-1,3,4-oxadiazol-2-thiol (17). A series of electrophiles, 25a-o, were synthesized by stirring primary amines (20a-o) with 3-bromopropanoyl chloride (24) in a basic aqueous medium. The target compounds, 26a-o, were synthesized by stirring 17 with synthesized electrophiles, 25a-o, in DMF using LiH as a weak base and activator. The synthesized compounds were initially confirmed through thin layer chromatography (TLC) and then finally corroborated through spectral data of IR (Infra Red), 1H-NMR (Proton Nuclear Magnetic Resonance), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance) and EIMS (Electron Impact Mass Spectrometry). Some spectra are also given for structural elucidation in the discussion section of chapter 4. The physical datalike color, state, yield, melting point (not for sticky solids), molecular formula and molecular mass of all the synthesized compounds also have been provided. Four enzymes, namely, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-Glucosidase and urease were used to establish the structure-activity relationship of all these synthesized bi-heterocyclic compounds. The antibacterial potential against different bacterial strains was conducted through thedisc diffusion method. Activity through diffusion method was compared with XIII Ampicillin. Doxorubicin was used as astandard to find out cytotoxicity of these synthesized compounds by killing brime shrimps at different concentration. All synthesized derivatives were computationally docked against AChE, BChE α-glucosidase, and urease to explore the binding modes of the ligands. Among the synthesized ninety (90) compounds, various compounds have shown pharmacological activity potential. The structure-activity relationship (SAR) of these synthesized compounds has been elaborated in chapter 4 under the discussion section. The most potent antibacterial agents and enzyme inhibitors with less toxicity might be subjected to in vivo study for further analysis as drug candidates. These compounds might be considered for the pharmacological industries as new drug candidates for a drug discovery program.