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 preliminary detection of products and their intermediates, along with their purity. The structures of two final compounds and their intermediates were proclaimed by melting point measurement, infrared spectrometry and ¹HNMR analysis given results greatly correspond with theoretical proposed chemical structure of synthesized compounds. Furthermore, cytotoxic activity evaluation on cell line level had been done for two final compounds against human breast tumor cell (MCF-7) and human ovarian tumor cell (SKO-3) types of cancer cell line and the results were confirmed which show greater cytotoxic tumor activity of two final compounds, while compound VI possess optimal activity proportional with increased number of 6-MP molecules.
Schiff bases (Sh1-Sh3) have been synthesized (p-aminophenol) was condensed with different aromatic aldehyde in ethanol inthe presence of glacial acetic acid as catalyst. These Schiff bases on treatment with monochloroacetyl choride gave 3-chloro-1-(4-hydroxyphenyl)-4-(substituted)azetidin-2-one(Az4-Az6), with αmercaptoacetic acid gave 3-(4-hydroxyphenyl)-2-( substituted)thiazolidin-4-one (Th7-Th9) and with anthranilic acid gave 3-(4-hydroxyphenyl)-2(substituted)-2,3-dihydroquinazolin-4(1H)-one (Qu10-Qu12). The purity of the derivatives was confirmed by TLC. The some compoundsidentify by (FT-IR and1H, 13C-NMR) data. Some of derivatives were evaluated activity against several microbesto determine ability to inhibit bacterial in some h
... Show MoreBackground: Methotrexate (MTX) was one of the first drugs synthesized for a specific chemotherapeutic purpose used to inhibit folic acid (FA) for the treatment of acute lymphoblastic leukemia in children. Its history is closely related to the discovery and characterization of folic acid. It is used clinically in medicine to treat a range of cancerous and noncancerous conditions. MTX is currently used in gynecology to treat disorders arising from trophoblastic tissue, namely, ectopic pregnancy. MTX, the most frequently used diseasemodifying anti-rheumatic drug (DMARD), suppresses disease activity and reduces joint damage. The aim of study: It is designed to demonstrate the effect of MTX (7.5 mg/wk.) on the histogenesis of gonad (testis) of n
... Show MoreOne of the important goals in the learning process is to be effective learning through the self-direction of the learner , because it has an impact on the effort of learners , it is better to be a learner responsible for learning and independent of the acquisition of knowledge ,
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... Show MoreThis work involved the successful synthesis of three new Schiff base complexes, including Ni(II), Mn(II), and Cu(II) complexes. The Schiff base ligand was created by reacting the malonyldihydrazide molecule with naphthaldehyde, and the final step involved reacting the ligand with the corresponding metallic chloride yielding pure target complexes. FTIR, 1 H NMR, 13 C NMR, mass, and UV/Vis spectroscopies were used to comprehensively characterize the produced complexes. These substances have been employed in this study to photo-stabilize polystyrene (PS) and lessen the photo-degradation of its polymeric chains. Several methods, including FTIR, weight loss, viscosity average molecular weight, light and atomic force microscopy, and energy disper
... Show MoreMethotrxate (MTX) has become the standard of care and first-line therapy for patients who have RA and consider as a gold standard of treatment for RA. The role of MTX in the treatment of RA has now been well established. The use of MTX treatment of RA inhibits proliferation of the lymphocytes, reduces signs and symptoms this disease, reduces progression damage of the joints and improves quality of life outcome. Progranulin (PGRN) acts a role in autoimmune inflammatory, has important function in several processes including immune response. Present study has conducted to find the effect of MTX drugs as a therapeutic target for RA patients because of its ability to bind with tumor necrosis factor receptor (TNFR), with progranulin, obestatin an
... Show MoreA new series of 5-methoxy-2-mercapto benzimidazole derivatives were synthesized by the reaction of 5-methoxy- 2-mercaptobenzimidazole with chloroacetic acid and affords 2-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio) acetic acid (1),which on cyclization with acetic anhydride and pyridine gives 7- methoxybenzo[4,5]imidazo[2,1-b]thiazol- 3(2H)-one(2), which on condensation with different aryl aldehydes in the presence of anhydrous sodium acetate in glacial acetic acid, furnishes a arylidene thiazolidinone. The purity of the synthesized compounds was confirmed by melting point and TLC.The structures were established by different spectral analysis such as FTIR,1HNMR, and CHN analysis. The newly synthesized compounds (3a-d) were in vivo evaluated f
... Show MoreMethotrexate (MTX), a folate antagonist agent, is mainly used in treatment of malignant tumors and autoimmune diseases. The present study was undertaken to determine whether antioxidant vitamin (vitamin A) could ameliorate methotrexate induced oxidative stress in male rabbits. Twenty male rabbits were randomly assigned into four groups. Group 1: control group, Group 2: MTX-treated group (received 20 mg/kg MTX intraperitoneally), Group 3: Vit.A treated group received 5000 IU Vit.A orally) and Group 4: MTX+Vit.A treated group received MTX 20 mg/kg plus 5000 IU vit.A). After 4 weeks of treatment, blood samples were collected by cardiac puncture to determine the serum malondialdehyde (MDA), as a good indicator for lipid peroxidation and
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