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ڈاکٹر عبدالعلیم

ڈاکٹر عبدالعلیم
ڈاکٹر عبدالعلیم سابق وائس چانسلر مسلم یونیورسٹی علی گڑھ اور صدر اردو بورڈ دہلی کی اچانک وفات سے پورے علمی حلقہ کو دکھ ہے، ان کے خیالات کچھ بھی رہے ہوں، لیکن وہ اپنی شرافت طبع اور مرنجان مرنج رویے کی وجہ سے ہر حلقہ میں پسند کئے جاتے تھے، جہاں رہے ان کا وزن اور وقار رہا، دارالمصنفین سے ان کے تعلقات برابر خوشگوار رہے، مسلم یونیورسٹی کے عربی اور اسلامیات کے شعبوں کو ترقی دینے میں بھی ان کی خدمات برابر یاد کی جائیں گی، وہ مسلم یونیورسٹی کے وائس چانسلر بہت ہی نازک دور میں بنائے گئے، ان پر نظر انتخاب ڈاکٹر ذاکر حسین خاں مرحوم کی پڑی تھی، جو ان کو بہت محبوب رکھتے تھے، انھوں نے جامعہ ملیہ میں تعلیم پائی، ان کی وفات سے جامعہ ایک لائق فرزند علمی حلقہ ایک شریف اہل علم اور ملک ایک بہت ہی باوقار محب وطن سے محروم ہوگیا، اﷲ تبارک و تعالیٰ ان کو غریق رحمت کرے، آمین۔ (صباح الدین عبدالرحمن، مارچ ۱۹۷۶ء)

 

Mitogen Activated Protein Kinase: Function and Responses to Different Stresses in Plants

Mitogen Activated Protein Kinase (MAPK) pathway is the most commonly studied signaling mechanisms, consisting of different groups of protein kinases that participate in regularly connecting interpretation of external stimuli that can change in gene expression or cellular organization within eukaryotic systems. The MAP kinase pathways functions in plants cell signaling (intra- and extra). MAPK cascades follow a response system. MAP kinases are the component of kinase constituents that deliver signals from sensors to responders in eukaryotes including plants. Several pathways are activated under different environmental stresses. Stimulating agents may be biological (biotic) like microbial infections or environmental (abiotic) like temperatures threshold, high salt concentration, drought, heavy metal, Ultra-violet radiation, ozone gases and reactive oxygen species (ROS). The involvement of MAPK signaling pathway in different stresses has been widely studied. In this review we also try to highlight MAPK cascades, its regulation, functions and recent findings in various cellular processes against stress conditions.

Studies on Anticancer and Antileishmanial Potentials of Synthetic Compounds and Insight into Anticancer Mechanism of Selected Organotin Iv Compounds

Drug development has multiple stages of drug designing and evaluation in pharmacological models for desired clinical outcomes. The unmet need to completely eradicate cancer and leishmaniasis drives researchers to continue the struggle for safer and effective medicines. Along these lines, a library of 78 organic synthetic compounds including organotin (IV) (39), indoline (15), hydrazide (4), diazole (2) and ferrocene (18) derivatives were studied against Leishmania and cancer using in vitro, in silico and in vivo models. Cytotoxicity against DU145, THP-1 and isolated lymphocytes was shown by 36 (> 70%), 21 (> 50-70%), and 18 (least IC50 2.23 µg/ml) organotins and 1 (75.72%), 4 (50.2-82.3%) and 2 (least IC50 13 µg/ml) indolines, respectively. Only 5 (50.08-81.7%) hydrazides/diazoles and 9 (least IC50 6.66 µg/ml) ferrocenes were cytotoxic to THP-1 cells and lymphocytes, respectively. A total of 38 (least MIC 0.0122 µg/disc) organotins, 1 (least MIC 3.125 µg/disc) indoline, 3 (least MIC 1.5625 µg/disc) diazole/hydrazides and 17 (least MIC 0.74 µg/disc) ferrocenes demonstrated protein kinase (PK) inhibition activity in Streptomyces 85E. Next, in silico analysis of selected 36 organotin (IV) compounds, comparatively more cytotoxic to cancer cells, showed that these were druglike to mid structures, have low to high blood brain barrier penetration and human intestinal absorption (caco2 cell permeability 17.6-35.09 nm/sec) and were metabolized by phase I and phase II reactions. Organotins were also predicted to target multiple enzymes, transcription factors, receptors, transporters, ion channels and other proteins. Subsequently, in vitro cytotoxicity analysis in prostate cancer cell lines and fibroblasts provided least IC50 values of 0.17 µM (PC3M) and 1.67 µM (fibroblasts) for triphenyltin (IV); 0.63 µM (PC3M) and 0.12 µM (fibroblasts) for tributyltin (IV); 0.33 µM (PC3M) and 2.55 µM (fibroblasts) for dibutyltin (IV) and 6.06 µM (PC3M) and 4.29 µM (fibroblasts) for tribenzyltin (IV) compounds after 72 h of treatment. Eventually, in-depth study of two most active compounds namely dibutylstannanediyl (2Z,2’Z)-bis(4(benzylamino)-4-oxobut-2-enoate (Ch-620) and triphenylstannyl 2-(benzylcarbamoyl) benzoate (Ch-319), showed that both compounds were more cytotoxic to prostate cancer and melanoma cells as compared to normal cells, restricted their colony forming capacity and migration, induced cell cycle arrest and caspase mediated apoptosis and disrupted associated regulatory proteins. Ch-620 resulted in phosphorylation of p38 MAPK and ERK1/2, upregulation of PPARα, decreased expression of SMAD4 and ITGB5 and reduced tumor proliferation as observed by proteomics, in vitro and in vivo xenograft studies. Treatment of cancer cells and transgenic Pten knockout mice with Ch-319 downregulated PI3K/Akt signaling associated with elevation of FOXO3a expression. In addition, Ch-319 decreased expression of epithelial-mesenchymal transition markers Ncadherin and Vimentin with concomitant increase in E-cadherin in in vitro. Immunohistochemical examination of tumor sections also depicted reduction of proliferation markers. Moreover, evaluation of 78 compounds against Leishmania tropica kwh showed that 37, 5 and 1 organotin, indoline and ferrocene compounds, respectively inhibited growth of promastigotes. The selected 43 compounds predominantly organotin (IV) derivatives, halted the growth of Leishmania promastigotes partially by producing reactive oxygen species. Antileishmanial activity was reduced by 4.1-6.9 and 1.4-7.96% in triphenyltin (IV), 3.3-14.22 and 6.3-11.2% in tribenzyltin (IV), 5.2-34.38 and 1.838.2% in tributyltin (IV) and 7.9-15.7 and 5.2-15.4% in dibutyltin (IV) compounds in the presence of sodium azide and mannitol, respectively. Indolines and ferrocenes demonstrated antileishmanial activity reduction maximally in the presence of mannitol by 5.3 and 6.22%, respectively. Considering all these results, it is proposed that Ch-319 and Ch-620 have potential to be developed as anticancer agents against prostate cancer. Furthermore, organotin (IV) compounds in particular are also potent antileishmanial agents and detailed analysis on their mechanism is recommended.
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