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Cephalothin as a Carrier of 6-Mercaptopurine for Targeting Cancer Tissues

A lower extracellular pH is one of the few well-documented physiological differences between tumour and normal tissues. On the other hand, elevated glutathione (GSH) level has been detected in many tumours compared with healthy surrounding tissues. The compound II: 3-(9H-purin-6-yl-thio) carbonothionyl methyl-8-oxo-7-(2-thiophen-2-yl) acetamido-5-thia-1-azabicyclo-4-octo-ene-carboxylic acid was a cephalothin derivative contain 6-mercaptopurine (6-MP). Compound II react with general base catalysis in slightly acidic pH or with sulfhydryl nucleophiles to release the chemotherapeutic drug 6-MP. The generation of compound II was accomplished following multistep reaction procedures. The structure of compound II and its intermediate was confirmed by their melting point, infrared spectroscopy, CHN and NMR analysis. The hydrolysis of compound II in aqueous buffer solution of pH 6 and in the presence of GSH at pH 7.4 was studied. The partition coefficient (PC) of compound II was also determined. Compound II has acceptable rate of hydrolysis at slightly acidic medium pH 6 (t1/2 = 56.34 min.) and 80% of compound II had been converted to 6-MP within 30 min in the presence of GSH. And the compound has acceptable stability at pH 7.4(t0.5=639.65 min.) and the rate of hydrolysis was effected by change the buffer concentration.  This compound can selectively deliver 6-MP into the tumour tissues which have acidic pH or elevated GSH level. Compound II had an improved PC value of 12.23 compared to 1.22 for free drug 6-MP confirming higher lipophilicity.

Key words: 6-mercaptopurine, cancer, prodrug, targeting

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Publication Date
Tue Feb 01 2022
Journal Name
Macromolecular Symposia
Synthesis of 5‐Fluorouracil–Naproxen Conjugates as a Mutual Prodrug for Targeting Cancer Tissues
Abstract<p>A new 5‐fluorouracil–naproxen conjugate is synthesized as a mutual prodrug for targeting cancer tissues. The structure of the target compound and their intermediate are characterized by their melting point, IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and elemental microanalysis. The cytotoxic activity is preliminarily evaluated using nonsmall lung cancer CRL‐2049, human breast cancer CAL‐51, and one type of normal cell line; rat embryo fibroblast cell line. The synthesized compound shows a good cytotoxic effect at the cancer cell and no significant effect at rat embryo fibroblast cell line.</p>
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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis of 5-Fluorouracil Derivatives as Possible Mutual Prodrugs with Meloxicam and Ibuprofen for Targeting Cancer Tissues

In the present study, five derivatives have been designed to be synthesized as possible mutual prodrugs for 5-Fluorouracil (5-FU) and non steroidal anti-inflammatory drugs (NSAIDs) to selectively deliver the drugs into the cancer cells. The synthesis of the target compounds were accomplished following multistep reaction procedures, the chemical reaction followed up and the purity of the products were checked by TLC. The structure of the final compounds and their intermediates were confirmed by their melting points, infrared spectroscopy and elemental microanalysis, the hydrolysis of compound III was studied using HPLC technique. According to the results mentioned above, compounds (I−V) can be good candidates as possible mutual prod

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Publication Date
Wed Apr 01 2020
Journal Name
Biochem. Cell. Arch.
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Publication Date
Sun Jun 09 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Anticancer Evaluation of 6-Mercaptopurine –Methotrexate Conjugate as Possible Mutual Prodrug

Small molecules drug conjugate mutual prodrug design  (SMDC) composed of folate and lethal agent conjugate, rigidly bonded via hydrophilic bridge and self immolative disulfide  bond   ;  represent new interesting approaches for cancer treatment , the component of SMDC intended  for targeting    folate receptor , along with greater conservation  of component until reaching  the target tumor tissue . The  designing and synthesis of compound VI and VIII derived from 6-Mercaptopurine (6-MP) and Methotrexate ( MTX) conjugate altogether as mutual prodrugs were  processed forward  successfully by multistep reaction  procedures , and by Thin Layer Chromatography (TLC) for

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Publication Date
Sun Jan 01 2023
Journal Name
Materials Today: Proceedings
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Publication Date
Sun Jan 01 2023
Journal Name
Materials Today: Proceedings
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Publication Date
Thu Apr 18 2019
Journal Name
Al-kindy College Medical Journal
Immunohistochemical Targeting of p110β Isoform of phosphatidylinositol 3-kinase co-associated with Cyclin-Dependent Kinase 1 in a Group of Tissues from Iraqi Patients with Breast Cancer

Background: While two-thirds of breast cancers express hormone receptors for either estrogen (ER) and/or progesterone (PR) , genetically altered PI3K pathway was found in more than 70% of ER-positive breast cancers.An aberrant activity of cyclin-dependent kinase 1 (CDK1) in a wide variety of human cancers has selectively constituted an attractive pharmacological targets in MYC-dependent human breast cancer cells.

Aim of the study:  Role of p110-beta as well as and CDK 1  in the pathogenesis of subset of breast cancers and contribution in their carcinogenesis.

Type of the study: is a retrospective study

Methods: This retr

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Publication Date
Wed Jan 01 2020
Journal Name
Annals Of Tropical Medicine And Public Health
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Publication Date
Thu Dec 09 2021
Journal Name
Revista Latinoamericana De Hipertension
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Publication Date
Wed Jan 30 2019
Journal Name
International Journal Of Applied Pharmaceutics
THE IMPACT OF NEW TARGETING METHODS IN THE CANCER THERAPY

Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later

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