Synthesis, structural characterization, and antiproliferative/cytotoxic effects of a novel modified poly (maleic anhydride-co-vinyl acetate) doxorubicin conjugate

Autor: Haci Bayram Zengin, Mesut Karahan, Gulderen Karakus, Ayse Sahin Yaglioglu, Abdulilah Ece
Přispěvatelé: Biruni Üniversitesi, [Karakus, Gulderen] Cumhuriyet Univ, Dept Pharmaceut Chem, Fac Pharm, TR-58140 Sivas, Turkey -- [Ece, Abdulilah] Biruni Univ, Dept Pharmaceut Chem, Fac Pharm, TR-34010 Istanbul, Turkey -- [Yaglioglu, Ayse Sahin] Cankiri Karatekin Univ, Fac Sci, Dept Chem, TR-18100 Cankiri, Turkey -- [Zengin, Haci Bayram] Cumhuriyet Univ, Dept Chem, Fac Sci, TR-58140 Sivas, Turkey -- [Karahan, Mesut] Uskudar Univ, Fac Engn & Nat Sci, Dept Bioengn, TR-34662 Istanbul, Turkey, Ece, Abdulilah -- 0000-0002-3087-5145, Karahan, Mesut -- 0000-0002-8971-678X
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Materials science
Polymers and Plastics
Hydrochloride
Stereochemistry
Electrostatic potential counter map
HeLa and C6 Cell Lines
02 engineering and technology
Benzoyl peroxide
010402 general chemistry
01 natural sciences
HeLa
chemistry.chemical_compound
polycyclic compounds
Materials Chemistry
Vinyl acetate
medicine
Poly(maleic anhydride-co-vinyl acetate) modification
Antiproliferative and Cytotoxic Activity
Computational Study
biology
technology
industry
and agriculture
Maleic anhydride
Doxorubicin hydrochloride
General Chemistry
Doxorubicin Hydrochloride
Poly (Maleic Anhydride-Co-vinyl Acetate) Modification
021001 nanoscience & nanotechnology
Condensed Matter Physics
biology.organism_classification
Electrostatic Potential Counter Map
0104 chemical sciences
chemistry
Antiproliferative and cytotoxic activity
HeLa and C6 cell lines
Computational study
0210 nano-technology
Drug carrier
Nuclear chemistry
Conjugate
medicine.drug
Popis: WOS: 000400971300013
Drug carrier, poly(maleic anhydride-co-vinyl acetate) (MAVA or poly[MA-co-VA]) copolymer, was traditionally synthesized by free radical chain polymerization reaction, in methyl ethyl ketone (MEK) organic media at 80 A degrees C, using benzoyl peroxide (BPO) as the radicalic initiator. The purified copolymer was then modified with a chemotherapeutic agent, doxorubicin hydrochloride (DOX) at 75 A degrees C for 72 h, using N-(3-dimethyl-aminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) as the carboxylic acid-activating agent. Structural characterization of the MAVA and the modified MAVA/DOX conjugate was carried out by Fourier transform infrared (FTIR) and nuclear magnetic resonance (H-1-NMR and C-13-NMR). Their molecular weights were determined by size-exclusion chromatography (SEC). The spectroscopic and SEC results confirmed that conjugated/modification reaction was successfully carried out. UV spectrophotometric measurements indicated that MAVA/DOX preserved its molecular stability in physiological body fluid, PBS (physiological pH 7.40 at 37 A degrees C). Antiproliferative activities of MAVA/DOX were determined by BrdU cell proliferation ELISA assay using C6 (Rat Brain tumor cells) and HeLa (human uterus carcinoma) cell lines in vitro by comparing with free DOX agent (reference compound). Although MAVA showed low antiproliferative activity, both MAVA/DOX and DOX exhibited greater activity against HeLa and C6. Lactate dehydrogenase (LDH) leakage assay was performed for MAVA/DOX and DOX, which detected a non-toxic effect against C6 even at the highest dose (100 mu g/mL). IC50 and IC75 values were also determined using ED50 plus v1.0. Molecular modeling at M06-L/6-31 + G(d,p)//AM1 level showed that the electron density in MAVA/DOX is more localized resulting a higher polarization and thereby a higher dipole moment which shed light on the solubility of MAVA/DOX conjugate.
Sciences Research Projects Foundation of Cumhuriyet University [F258, F339]
This work was supported by Sciences Research Projects Foundation of Cumhuriyet University (Project No: F258 and F339). Structural characterizations were carried out at Technology Research and Developing Centre, Erciyes University, Kayseri, Turkey. Average molecular weight distribution of MAVA and MAVA/DOX was analyzed by Size-Exclusion Chromatography (SEC) Measurements at Yildiz Technical University.
Databáze: OpenAIRE
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