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Benzimidazole and Acetamide Derivatives As Potential Therapeutic Agent for Breast Cancer

Thesis Info

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Author

Aziz, Aisha

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Pharmacology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11670/1/Aisha%20aziz%20pharmacology%202019%20UoK.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725571975

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Breast cancer is the most prevalent disease in women all-around the world. It is the leading cause of death in women. About 0.5 million deaths of breast cancer are reported worldwide. Options available for breast cancer treatment are surgery, radiation therapy and chemotherapeutics, e.g., doxorubicin, paclitaxel and cyclophosphamide. To improve therapeutics in breast cancer there is a need to develop better compounds with good efficacy and fewer side effects. The prime objective of present study is to analyze the activity of acetamide derivative, N-(2-hydroxyphenyl) acetamide (NA-2) and benzimidazoles derivative, 2-Amino-1 Me Benzimidazole (3Ve) on human breast cancer cell line MCF-7. Cytotoxic effects of NA-2 and 3Ve was determined by MTT assay. Doxorubicin was used as a standard drug in this study. Both NA-2 and 3Ve have shown dose dependent growth inhibition of MCF-7 cell line following 48h treatment. To explore the effects of these compounds on the mechanisms of apoptosis, cell cycle, angiogenesis and proliferation the cells were treated with IC50 doses of these drugs. The process of wound healing was assessed by scratch assay. Both the compounds delayed the wound healing process significantly. The effect of these compounds on cell cycle stages was monitored by flowcytometry. Both NA-2 and 3Ve arrested the cell cycle at G0/G1 phase and DOX has shown G2/M arrest. The apoptosis was assessed though ANNEXIN-V FITC assay. The morphology was seen by using fluorescent microscope and quantification was done by flowcytometry. The cells after treatment with the test compounds and standard have demonstrated the morphology of apoptotic cells. NA-2 and DOX produced late appearance of apoptotic events and 3Ve resulted in early apoptosis. The effects of NA-2, 3Ve and DOX on BAX (proapoptotic) and BCL2 (antiapoptotic) were also studied. Following 48 hours treatment, NA-2, 3Ve and DOX have enhanced BAX expression and attenuated BCL2 expression as compared to untreated control group. The results were also significant when we studied the effects of the compounds on BAX/ Bcl 2 on protein expression level by immunocytochemistry. Angiogenesis was assessed by using the markers VEGF and AKT. To observe antiangiogenic effect of the compounds RT-PCR was performed but none of these was effective to decrease the gene expression of XIV aforementioned markers.The anti proliferative effect of the compounds was further assessed by cellular markers of signal transduction pathway involved in breast cancer progression. These are JAK1, JAK3, STAT2 and STAT5A, which are highly expressed in breast cancer. The effects of the compounds were assessed on both gene and protein expression level. The results of both the compounds were found more significant on JAK 1 and STAT 2 expression levels. The same pattern was seen with Doxorubicin. While in case of JAK3, NA-2 did not diminish either gene or protein expression while 3Ve and DOX decreased the expression at genetic as well as protein level. The gene and protein expression of STAT5A following 3Ve treatment decreased after 48 h significantly. NA-2 and DOX were only effective to diminish the protein expression of STAT5A. We therefore draw a conclusion that NA-2 and 3Ve can inhibit proliferation of breast cancer cell line MCF-7 by induction of apoptosis and arrest of cell cycle at different stages. NA-2 and 3Ve have also attenuated different markers of JAK/STAT pathway.
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پروڈکشن کے نام پر جنسی استحصال

پروڈکشن ہاؤس کے نام پر جنسی استحصال

                یہ ناول نگار کا مشاہدہ ،تخلیق اور تحقیق ہے جو انھیں دوسروں سے نمایا ں کرتی ہے۔وہ بے باکی سے اپنامدعا بیان کرتے ہیں۔ناول نگار نے ظفر عالم کا ذکر کیا ہے کہانی میں جو کہ پروڈکشن ہاؤس چلاتے ہیں اور ان کی بیگم وہاں پہ ٹیچر ہیں۔وہ لڑکیوں کو پروڈکشن کے کام سکھاتی ہیں۔ضامن کی جب ان سے ملاقات ہوئی تو وہ اسی کشمکش میں تھا کہ وہ ضامن سے کیوں ملنا چاہتے ہیں۔پہلے ہی اس کے دل ودماغ میں ذیشان اور شیزہ کے حوالے سے سوالات کے انبار تھے۔ضامن نے ظفر عالم سے ملاقات کے بعد  اس کے نتائج بھی کچھ یوں نکالے:

’’مجھے یہ شخص پورے سسٹم کا مرکزی کردارمعلوم ہورہا تھااور اس کی بیوی جسے وہ ٹیچر بتارہاتھا۔میں اچھی طرح جانتا تھا یہ شوبز ڈیزاننگ انڈسٹری دوسرے لفظوں میں سیکس انڈسٹری ہوتی ہے‘‘ (25)

                یہ ایک معمہ تھا۔ضامن کیلئے وہ الجھتا جارہا تھا۔ناول نگار کی تحریر شعور زیست کے ساتھ ساتھ شعار زیست بھی دیتی ہے جو قاری میں ترفع پیدا کرنے کا موجب بنتی ہے۔بہر حال قاری کے دل ودماغ کو شعور تب ملنا شروع ہوا جب ضامن، ذیشا ن اور شیزہ دونوں کے ساتھ ایک فلیٹ پر رہنے آگیا۔وہ ایک عجیب قسم کا فلیٹ تھاکبھی دوست آتے، بہت چہل ہوتی ،کبھی بہت خاموشی ،کبھی رقص کی محفل ،کبھی انتہائی بیزاری محسوس ہوتی تھی اور سب سے بڑھ کر ضامن جو شیزہ کی محبت میں گرفتار ہو کر فیصلہ نہیں کر پارہا تھاکہ ہو کیا رہا ہے۔

                ناول نگار نے بے پردگی کی ایک ایسی فضا قائم کی ہے جو قاری کو سوچوں میں گم چھوڑ دیتی ہے۔وہ سوچتا رہتا ہے کہ کیا اخلاقیات...

حلالہ اور مروجہ حلالہ سنٹرز: ایک تجزیاتی مطالعہ

Almighty Allah made marriage a source of affection and love among the human beings. He also ordered to uphold this relation as much as possible. If, on one way or the other the relationship of a couple becomes so unpleasant that their family life becomes impossible to move any more further. In this case the Islamic “Sharia’h” recommends opening of the ways for their respectable separation in the shapes of “Divorce” and “Khula’a” (divorce obtained on wife’s initiative, s). Though Islamic sharia’h has declared “Divorce” as legal act, yet marriage being a great sacred relation which is desired to be retained intact to the maximum, it has been named as the most unpleasant among the permissible acts in Islam. Some human beings very abruptly break the same relation (Nikah) without proper consideration. Some of these persons later on repent on what they have done. Allah Almighty  therefore, very affectionately has allowed men after uttering two times the words, ‘Divorcee (Talaq) at different times to reconcile with their wives. But if he disrespecting this great relation stress-passes the final time and utters the word “Divorce” (Talaq) for the third time in his life so the religion has fixed certain punishment for his this very irresponsible act as a punishment that though, both spouses may agree to continue their married life, Islam does not allow them to do so, prior to undergoing the process of re-marrying  the woman with another person to fulfill the condition of her reunion with her first husband. This process is called “Halala”  In the article under reference side by side with presenting the literal meaning and idiomatic definitions of Halala, its Shari status has also been elaborated. Efforts  have been intensified to recollect the different views of all jurists  regarding this practice and examine the same analytically. In addition to that with the help of irrefutable proofs, the adverse effects of the so called “Halala, s centers” have been proved to warn the people to stay away from them.

Implementation of Do-Talk-Record Strategy in Lower Secondary Mathematics Classroom in Government School

Teaching and learning mathematics is considered a boring and difficult task by the teachers as well as students where teachers have to take whole responsibility of transferring mathematics knowledge to students and students fearfully receive this knowledge as passive recipients. My experiences a learner and later as a teacher in the same situation has stimulated my thinking about a better and effective way of teaching and learning mathematics which could invite students' active participation in their own learning. Hence I took the opportunity to conduct a study according to my interest in mathematics teaching. The focus of my study was the implementation of the Do - Talk - Record strategy in lower secondary mathematics' class in a government school. The research was carried out for five weeks and the study was designed to follow three stages (pre-intervention, intervention and post-intervention). I followed a qualitative research design because qualitative research seeks to enlarge our sense of explanation and makes things understandable by means of explanation or interpretation. The observation of classroom practice, interview of research participants and my own teaching helped me with data collection. During the pre-intervention stage, I found that the teacher's current emphasis was on rote learning. Students blindly followed the procedure directed by the teacher. The purpose of my study was to create an environment for the students in which they became self learners and, they would relate mathematics to their daily life with anintent to promote long-term memory. Through the Do - Talk - Record strategy I tried to develop discussion skills in students. For that purpose I gave students some activities. During activities I recognised some teaching approaches which helped me to know how students learn; such as learning through misconception, learning through prior knowledge, learning by doing, learning by questioning and learning through discussion. I used those approaches which enabled me to support students' conceptual understanding of fraction'. The result of this approach enabled me to suggest some recommendations, like the Do - Talk - Record strategy be introduced in the educational institutions in Pakistan on a trial basis.