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New Bioactive Ferrocene Incorporated N, N′- Disubstituted Ureas and Thioureas

Thesis Info

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External Link

Author

Faiza Asghar

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/2911/1/Thesis%20Faiza-Final%20.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726750562

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In the present work, the synthesis, characterization (FT-IR, multinuclear ( 1 H and 13 C) NMR, AAS, elemental analysis and single-crystal XRD), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry) and in vitro biological screening of some ferrocene-based thioureas and ureas are reported. The ferrocene-incorporated N,N′- disubstituted thioureas 3a1-3d17 were derived by allowing the ferrocenyl anilines 2(a-d) to react with freshly prepared isothiocyanates in dry acetone. In the subsequent reactions, the deprotection of these thioureas 3a1-3d17 to the corresponding oxo analogues using NaOH (aq) and mercuric chloride led to the ferrocenyl ureas 4a1-4d17 in high yields. Crystallographic analyses of representative compounds revealed a supramolecular structure mediated by secondary non-covalent interactions (π---H and π---π), which facilitated the interaction of these molecules with biological macro-molecules like DNA. DNA binding is a pre-requisite for a compound to be used as an antitumor agent. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The diffusion coefficients of the drug-DNA adducts are lower than is that for the free drug indicating slow diffusion of the comparatively high molecular weight drug towards the electrode in the cyclic voltammetric study. The small binding site size (s) values are also indicative of an electrostatic mode of interaction. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good free radical scavenging activity against DPPH. These compounds were also screened for antimicrobial, cytotoxic (brine shrimps) and protein kinase inhibition potential and proved to be effective candidates in terms of microbial growth and protein kinase inhibition. The synthesized complexes were scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of XIcytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin). The presence of electron-withdrawing substituents was found to exert profound influence on the therapeutic properties of these compounds, which might be attributable to the decrease in the basicity of the NH groups and an increase in their lipophilicity. These properties may prove valuable in the future design of new anticancer and antimicrobial drugs.
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کبھی نگاہوں کی چلمنوں سے نہ راز کہنا، فضا سے کہنا

کبھی نگاہوں کی چلمنوں سے نہ راز کہنا، فضا سے کہنا
غمِ جہاں کو تو زندگی بھر پڑے گا سہنا، فضا سے کہنا

رفاقتوں کا ہے دعویٰ تم کو تو اپنے دعوے کی لاج رکھنا
زماں، مکاں کی حدوں سے آگے بھی ساتھ رہنا، فضا سے کہنا

قدم قدم پر ہے خطرۂ جاں، وہ عزم اپنا بلند رکھے
یہ عشق دریا ہے اس کی فطرت ہے الٹا بہنا، فضا سے کہنا

وہ شوخ آنکھیں غزال جن پہ ہیں صدقے واری، مَیں کیوں نہ واروں
یہ چاند، بادل، دھنک، بہاریں، یہ حسن گہنا، فضا سے کہنا

گلوں نے کلیوں نے کترے دامن، قزح بھی آنکھیں چھپا رہی ہے
یہ نازکی کا لباس تم نے غضب ہے پہنا، فضا سے کہنا

Arrhythmias after Implantation of the Left Ventricular Assisted Device Arrhythmias after Implantation of the Left Ventricular Assisted Device

Cardiac arrhythmias has been frequently reported after left ventricular assist devices implantation but currently literature shows no sufficient information on cardiac arrhythmias. Objective: The aim of this study was to assess the frequency and other features of ventricular and supra ventricular ectopic beats ((SVEB), atrial fibrillation (AF)/flutter (AFL) post device implantation. Methods: This is a retrospective study conducted in Department of Cardiac-Surgery, University of Verona Medical School, Verona, Italy from June 2014-September 2016. Rhythm monitoring and registration were collected from 16 patients (13 males; 45±13years) during the first five (05) days after implantation. To assess late post-operative rhythm, patient’s hospital electronic records were used as well asfunctional hemodynamic parameters including mean arterial pressure(MAP), right atrial pressure(RAP), heart rate(HR) and ST-deviation(d-ST). Results: Ventricular arrhythmia (n=9), atrial fibrillation (n=5) or atrial flutter (n=2) episodes were preoperatively present in 11 patients. Postoperatively, 5 patients developed either VT (n=2), AF (n=1) or both VT/AF (n=2) during a follow-up of 18±14 months. Prior to postoperative VT (POVT) episodes (n=123), MAP decreased, HR, d-ST increased and RAP remained unaltered. POVT were initiated either by single VEBS (28%), V-couplets (15%), V-run (46%) or occurred suddenly (11%). Conclusions: Ventricular and supraventricular arrhythmias are common after device implantation. The frequency of sustained VTA was less at early phase as compared to late postoperative phase.

Going Concern Prediction Models of Liquidated Non-Financial Firms of Pakistan.

The main focus of this study is whether the original version of the prediction models are the best proxy for evaluating the firm’s status as going concern that are operated in creditor-oriented regime. This study is much more precise for the selection of firm as an analysis sample to formulate the prediction model for the firm that are operated in the creditor-oriented regime. The selection is based on such type of firms, whose: a) continuous financial years net losses, b) the external and independent auditors issue the non-going concern opinion of the audited client, and c) all the operations of firms are liquidated. The analysis sample consist of one hundred and twenty-four (124) non-financial firms. In first stage, the validity of the original version of the existing firm’s bankruptcy prediction models, like Altman (1968) and Rashid and Abbas (2011); the original version of the existing going concern prediction models, like Koh and Killough (1990), and Koh (1991); and the original version of the existing liquidation prediction models, like Kuruppur, Laswad and Oyelere (2003) are examined. In second stage these aforesaid models are re-estimated (or updated) and the revised prediction models are formulated for the firms that are operated in creditor regime. In third stage, this study formulated the prediction models by using the MDA and LR techniques to deal with the issues faced by the auditor for evaluating the firm’s status as going concern. The type I error and type II error of the formulated prediction models for evaluating the firm’s status as going concern is less than the type I error and type II error of the existing firm’s prediction models, re-estimated (or updated) version of the existing firm’s prediction models and new prediction models based on the pool of variables. The proposed prediction models are considered as the best alternative for evaluating the firm’s status as going concern. The finding based on five (5) discriminatory ratios that are the part of statement of profit and loss, and the statement of financial positions, the newly formulated prediction models, consist of accounting ratios, is not only a useful tool for accessing the firm’s status as going concern, but also a supportive tool for accessing the firm’s financial fraud risk, for the external and independent auditors in order to construct their opinion for a firm that is operated in the creditor-oriented regime. Implication that emerge from these results has developed the instrument which will be highly recognized by the accounting and auditing practitioners like the auditors of developed economies. Therefore, the regulatory authorities in Pakistan, like SECP, SBP and PSX; and the audit practitioner institutes, like ICAP, and ICMAP, to use these formulated the prediction models for evaluating the firm’s status as going concern that are operated in creditor-oriented regime. The proposed models would also be helpful in monitoring and assessing the financial health of the firms as well.