شیخ ظہور الحسن
افسوس ہے کہ شیخ ظہورالحسن صاحب سابق ریوینیو سکریٹری حکومت اتر پردیش نے کراچی میں انتقال کیا، وہ اپنے محکمہ کے ماہر اور اس صوبے کے لائق ترین عہدہ داروں میں تھے، حکومت میں ان کا بڑا وقار تھا، عملاً بڑے مذہبی اور دیندار تھے، مذہبی مطالعہ وسیع تھا، دینی کاموں سے بڑی دلچسپی تھی، ترک وطن سے پہلے دارالمصنفین کی مجلس انتظامیہ کے رکن تھے، کئی سال ہوئے ریٹائرڈ ہوچکے تھے، ان کے لڑکے پاکستان میں بڑے عہدوں پر تھے، لیکن وہ خود ہندوستان ہی میں مقیم رہے، ۱۹۶۵ء کی جنگ سے کچھ پہلے لڑکوں سے ملنے کراچی گئے تھے، اسی دوران میں جنگ چھڑگئی، اس لیے لڑکوں کے اصرار سے وہاں مستقل قیام اختیار کرلیا، اور وہیں قلبی دورے میں وفات پائی، مسلمان عہدہ داروں میں ایسے لائق اور دیندار کم ہوتے ہیں، اﷲ تعالیٰ اس مرد مومن کی مغفرت فرمائے۔ (شاہ معین الدین ندوی، جنوری ۱۹۷۲ء)
The Islamic laws prevent us from the evil deeds. As well as, according to Shariah, it is permissible and sometimes even compulsory to save the believers from the actions that may lead them towards the banned activities. Therefore, the ruling of prohibition from these types of activities is called Sadd-e-Zaree’a. This is the principle extracted from the Quran and Sunnah. As Almighty Allah forbade the believers to say ‘Ra’ina’ because this word was used by Jews knowingly in a wrong manner with evil intentions, whereas, Muslims presented their requests by this same word in the highest court of The Holy Prophet (peace and blessings be upon him) for seeking easiness and relaxation in their concerned matters. As in Quran: O People who Believe, do not say (to the Prophet Mohammed- peace and blessings be upon him), " Ra’ina (Be considerate towards us)" but say, " Unzurna (Look mercifully upon us)", and listen attentively in the first place. [Baqarah 2: 104]. (To disrespect the Holy Prophet – peace and blessings be upon him – is blasphemy.) Another example by Hadith, in this regard, it is also evidenced by the good character of The Holy Prophet (peace and blessings be upon him) that sometimes He stopped himself intentionally from the permissible activities lest the common masses may involve in undesired activities on the basis of The Holy Prophet’s act. Concisely, keen consideration is required on rational basis when explaining the Shariah rulings of any matter. Otherwise, the beauty andbenefits of the Shariah may be lost. Consequently, to prevent from the future turmoil is actually the spirit of Sadd-e-Zaree’ah. As this is the actually basic need and prerequisite of Shariah. It saves and prevents its believers form expected turmoil. Therefore, if the risk of turmoil would trigger with committing the permissible activity it must be abandoned due to the risk of turmoil.
This study was designed to study various classes of synthetic organic compounds for their antioxidant activities in molecular and cellular models of oxidative stress. Etiology of numerous types of cancers has been linked with oxidative stress, especially, metastatic melanoma is known as a reactive oxygen species (ROS) driven tumor.In this study, five metastatic melanoma cell lines (A375, WM266-4, SK-Mel-28, BLM, and MV3), and two non-metastatic melanoma cell lines (WM-115 and Mel-HO) were used to detect ROS association with neoplastic transformation relative to normal cell lines wound healing fibroblast (CPD95) and normal human melanocytes (NHEM). However, corelation of ROS production with metastatic propensity of malignant melanoma cell lines could be found. Out of over 1,000 compounds evaluated during this study, 250 synthetic organic compounds showed free radical scavenging activity in the DPPH radical scavenging assay. From them 34 synthetic organic compounds (17 free radical scavengers with low to high free radical scavenging activity, along with 17 non-radical scavenger homologues) were selected for further biomolecular studies. These compounds were evaluated for their cytotoxicity, using the MTT assay. Eight different synthetic organic compounds of four different classes, pyrimidine derivatives 1 and 4, biscoumarin derivatives 10 and 11, thiazole derivatives 6 and 8, and aryl Schiff’s bases 13 and 15, were identified as potential anti-melanoma agents due to their cytotoxicity against both metastatic (A375, and SK-Mel-28), and non-metastatic cell lines (WM-115) cell lines. The identified potential anti-melanoma agents were further evaluated against normal cells lines wound healing fibroblast (CPD95) and normal human melanocytes (NHEM), and all of them were found to be non-cytotoxic against (NHEM). However, one of the bis-coumarin derivatives 11, one thiazole derivative 8, and both of the pyrimidine, derivatives 1 and 4 were found non-cytotoxic to the fibroblast cells. These compounds were further tested for their anti-migration properties. Both derivatives of the class thiazole, aryl Schiff’s bases, and bis-coumarins were found to behave as antimigration agents, wherase none of them affected intracellular ROS production of A375 cells. DNA synthesis inhibition activity of these compounds was also evaluated using the BrdU incorporation assay; all compounds were found to inhibit DNA synthesis in the metastatic melanoma (A375 cell line) cancer cells. A non-radical scavenger, bis-coumarin derivative 11 with anti-migration and anti-proliferation activities, was tested on 43 different kinases phosphorylation sites, and 2 related proteins (heat shock and tumor supressor) at two different time ponits using proteome profiler human phospho-kinase array assay. Compound 11 was found to target 40 different phosphorylation sites of 25 different kinases. The mammalian target of rapamycin (mTOR) pathway kinases (mTOR and PRS40), as well as tumor suppressor proteins (Tp53 and Chk-2 kinase) that are involved in melanoma cell growth and tumor suppression, respectively, were found to be the significant targets of compound 11. Compound 11 was also found to inhibit melanoma cell survival, and growth at gene level via inhibiting phosphorylation of STATs family of transcription factors through the JAK- STAT pathway. Compound 11 was also found to inhibit the melanoma cell survival and proliferation by inhibiting phosphorylation of ERK1/2, MSK1/2, and CREB via EGF and PDGF receptor-dependent, and intracellular redox-independent signaling pathways. Members of Src family of kinases implicated in melanoma migration/metastasis were found to be additional targets of this compound. Compound 11 was effective in inhibiting metastatic melanoma proliferation, and cell migration. For the first time it was identified as a novel anti-melanoma agent of the bis-coumarin class that could suppress the melanoma cell growth along with its metastatic propensity without affecting normal cells. Based on these findings, the lead compound 3,3''((3,5Dichlorophenyl) methylene) bis (4-hydroxy-2-H-chromen-2-one) (11) was identified as a potential anti-melanoma and anti-metastatic drug candidate.