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Studies of the Role of Gpr54-Kisspeptin Signaling in Endocrine Function of Primate Testes

Thesis Info

Author

Shahzad Irfan

Department

Deptt. of Animal Sciences, QAU.

Program

Mphil

Institute

Quaid-i-Azam University

Institute Type

Public

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2006

Thesis Completion Status

Completed

Page

ii, 53

Subject

Animal Sciences

Language

English

Other

Call No: DISS/M.Phil BIO/1755

Added

2021-02-17 19:49:13

Modified

2023-02-19 12:33:56

ARI ID

1676718690756

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۳۹۔ آتم کتھا

آتم کتھا

وہ مجھ سے اس وقت بچھڑا تھا

جب آنکھوں کے سیپ خوابوں کے موتیوں کوترستے تھے

جب جسم و جاںپر رنگِ بہار نہیں چڑھا تھا

جب روح احساسِ کرب سے نا آشنا تھی

زندگی کی حقیقت کا ادراک نہیں تھا

کوئی دوست تھا نہ دشمن

اب میرے پاس سب کچھ ہے

یادیں ،محرومیاں ،اذیتیں

کیسے انمول کھلونے ہیں

مگر افسوس بے فکری کی دولت چھن گئی

غیر مسلم اقلیتوں کے حقوق کا اسلامی فلسفہ: قرآنی تناظر میں تجزیاتی مطالعہ

Islamic Philosophy of the Rights of Non-Muslims Minorties: An Analysis in Qur’ᾱnic Perspective Islam is complete code of life for entire humankind. According to the Holy Quran all human beings have been created from a single person (Adam). By birth all are equal and have all fundamental rights irrespective of their religion. If a group is numerically inferior to the rest of the population of state in a non-dominant position, will not be considered minority according to Quran. Quran classify people into two different categories: believers and non-believers on the base of their belief instead of numerical value. Minorities enjoy all fundamental rights and freedoms in Islamic territory. This article demonstrates in the light of Quran that Islam does not discriminate between Muslims and non-Muslims in the matter of rights and will clarify the objection of western propaganda that Islam is rigid for non-believers. There are different types of Non-Muslims living in Islamic state as minority. According to Quran, concept of minority is unique, minority does not mean inferior in number. This paper will reveal the types of minorities and their specific rights along with their basic rights too. It has been concluded that Islam is only religion which offers basic human rights at the level of equality irrespective their religion.

Complexes of Ruthenium and Osmium Based on Oxicam Scaffold As Potential Anticancer Agents

Metal based drugs have been used for medicinal purposes since ages but their potential was realized after the discovery of the first metal based chemotherapeutic agent, i.e., cisplatin, which became one of the most successful anticancer drugs espcecially for the treatment of testicular cancer. Other members of this class include oxaliplatin, carboplatin and nedaplatin. The use of platinum based drugs is limited due to their adverse side effects (e.g., nephrotoxicity, neurotoxicity, nausea, vomiting etc.) and intrinsic or acquired resistance. These limitations prompted bioinorganic chemists to develop new strategies to treat cancer with other metal based anticancer agents with higher efficacy and lesser undesired effects. Therefore, different metal complexes of titanium, iron, cobalt, gallium, ruthenium and osmium etc. were investigated. Among these NAMI-A (imidazolium [tetrachlorido(dimethylsulfoxide)(1Himidazole)ruthenate(III)]), KP46 (trismaltolate gallium) and KP1019 (indazolium trans[tetrachloridobis(1H-indazole)ruthenate(III)]) have enteredclinical trials. On the other hand, Ru(II)/Os(II) half sandwich organometallic complexes increase the lipophilic character of complexes and facilitate their uptake into cells. RAPTA type complexes are among the most popular examples of half sandwich organometallics. Furthermore, the coordination of bioactive ligands with these established organometallic pharmacophores may enhance the efficacy of these biologically active compounds by altering their physicochemical and pharmacological properties. In particular, the use of bioactive ligands such as hydroxypyrones, quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) often resulted in promising bioactivity of the compounds. In this thesis, the use of oxicam based NSAIDS as ligands for Ru(II) and Os(II) was investigated. For this purpose different series of ligands based on the oxicam scaffold were prepared. These include 1,2-benzothiazine based primary amides, secondary amides, indazole and methyl pyridyl based secondary amides, piroxicam as well as isoxicam analogues, 1,2-benzothiazine based α,βunsatuarated ketones and pyrazole based benzenesulfonamides. Furthermore, these ligands were reacted with Ru(II) and Os(II) cymene dimer to obtain organometallic complexes. All the ligands and complexes were characterized with different spectroscopic techniques including FT-IR, 1H, 13C NMR, elemental analysis, high resolution mass spectrometry and twenty seven compounds were analyzed by single crystal X-ray diffraction analysis. The cytotoxic activity of the complexes towards human colorectal carcinoma HCT116, non-small cell lung carcinoma NCIH460 and cervical carcinoma SiHa cells was investigated by using the sulforhodamine B (SRB) assay. The prepared ligands behaved as monodentate (N donor) or bidentate chelators (O,O-, N,O- and N,N-donor systems) depending upon the ligand structure as well as reaction conditions such as xxix nature of solvent used for reaction. The 1,2-benzothiazine based primary amides were synthesized by reacting compound 5 with different alkylating agents in basic conditions to isolate ligands 6a-g. These O,O-coordinating ligands were used to synthesize the organometallic ruthenium complexes 7a-g (Scheme-1) with piano-stool configuration. These complexes were evaluated for their anticancer activity and results indicate that only 7f and 7g were active against three different human cancer cell lines. On the other hand, 1,2-benzothiazine based secondary amides were synthesized by reacting compound 8 with different aniline derivatives to obtain O,O-chelating ligands 9a-g. When these ligands were reacted with [Ru(cym)Cl2]2, the same O,Ocoordination behavior was observed to stabilize metal complexes 10a-g by forming sixmembered rings and giving rise to piano stool type geometry (Scheme-2). All these complexes were found active against different anticancer cell lines and the most lipophilic compound was found the most active with an IC50 value of 13.58 µM. The N-benzyl analogues of piroxicam and isoxicam 11 and 12 were also prepared and reacted with MII(η6-p-cymene). Compounds 11 and 12 can act as monodentate ligands through their pyridyl/isoxazolyl nitrogen atom and as bidentate chelators to Ru(II) and Os(II) metal ions by forming six membered rings through pyridyl/isoxazolyl nitrogen and the amide oxygen atoms (Scheme-3). In compounds 15-18 functionalization at position 3 was carried out to get indazolyl/pyridyl goup-containing oxicam analogues which act as monodentate ligands and coordinate to ruthenium/osmium centres through pyridyl/indazolyl nitrogens. The results of anticancer activity studies revealed that organo-Ru(II) and -Os(II) complexes 18a-c are more active than the free ligand 18 (Scheme-4). The 1,2-benzothiazine based chalcones (Scheme-5) were obtained as intermediates which were reacted with hydrazine to isolate 1,2-benzothiazine based pyrazole containing sulphonamide ligands 21a-j. The results of anticancer activity assays show that halogen containing derivatives are more active in this series (Scheme-6). These pyrazole containing sulphonamides were reacted with [Ru(cym)Cl2]2 to isolate complexes in which these sulfonamides acted either asmonodentate or bidentate ligands. In complexes 22a-k ligands coordinated mondentately through the pyrazole nitrogen (Scheme-7) while in complexes 23a-g they coordinated bidentately via pyrazole and sulphonamide nitrogen atoms by forming rather stable seven membered rings (Scheme-8). The biological investigations indicate moderate to high IC50 values for these complexes and it was also observed that within the series of compounds, the most lipophilic complex was the most active.