- Preparation and characterization of micelles of oligomeric chitosan linked to all-trans retinoic acid
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New amphiphilic chitosan derivatives of all trans retinoic acid-chitosan (RA-chitosan) with different molar feeding ratios of all trans retinoic acid (ATRA) were synthesized. The degree of ATRA substitution ranged from 8.72% to 18.78%. The RA-chitosan formed micelles with an average size of 142.14-208.4 nm, and zeta potential of +27.25 to 34.48 mV. The critical association concentration (CAC) was found to range from 1.3 × 10-2 to 2.13 × 10-2 mg ml-1. Upon evaluation, the RA-chitosan shows no significant cytotoxicity on Hela and HepG2 cells. Analysis of micelles loaded with ATRA revealed that the size of micelles decreased by increasing loaded drug content while zeta potential did not change. ATRA was released slowly over 3-day period, and drug content had no effect on the release rate. These phenomena make RA-chitosan micelles as a candidate for drug carrier.
- Fattahi, Ali,Golozar, Mohammad-Ali,Varshosaz, Jaleh,Sadeghi, Hamid Mirmohammad,Fathi, Mohammadhossein
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- Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells
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As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.
- Bang, Eun-Kyoung,El-Baz, Karim,Hong, Jung Joo,Jeong, Dae Gwin,Kang, Kyung Won,Keum, Gyochang,Kim, Green,Kim, Hye-Jung,Kim, Jae-Ouk,Kim, Minjeong,Kim, Rhoon-Ho,Kim, Soo Young,Ko, Hae Li,Kwak, Hye Won,Lee, Hyukjin,Lee, Kyuri,Lee, Sang-Myeong,Nam, Jae-Hwan,Oh, Hanseul,Park, Hyelim,Park, Hyo-Jung,Ryu, Seung Rok,Song, Manki
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- Synthesis, Spectroscopy and Crystal Structure Analysis of N 1,N 3-dicyclohexyl-N 1-(all-trans-retinoyl)urea
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The title compound, C33H50N2O2, is a side product in the reaction of all-trans-retinoic acid (atRA) with N-hydroxysuccinimide, in the presence of the coupling agent N,N′-dicyclohexylcarbodiimide, which produces the ‘active’ ester succinimidyl all-trans-retinoate as the product. It crystallizes in the orthorhombic Pbca space group. The compound was characterized by 1H-NMR, 13C-NMR, ESI–MS and IR spectroscopy and its structure was determined by single-crystal X-ray diffraction. For example in the 13C-NMR spectrum, diagnostic peaks are those of the two amide carbonyl C atoms at δ 169.5 and 154.2?ppm, the ten olefinic C atoms of the unsaturated chain of atRA moiety at δ 149.0, 139.3, 137.7, 137.3, 134.9, 130.2, 130.0, 129.4, 128.5 and 121.5?ppm and the two methine C atoms of the N,N′-dicyclohexylurea moiety at δ 57.9 and 49.5?ppm. Detailed analysis of its molecular and supramolecular structure showed that close-packing principles (elongated shape/large hydrophobic region of the molecule) together with chemical factors (N–H?O and C–H?O intermolecular interactions) direct the 3D self-assembly process in the crystalline state. Hirshfeld surface analysis was employed, a powerful approach to quickly and easily gain insight into molecular environments in the crystalline state. Graphical Abstract: The synthesis and X-ray structure of 1-((2E, 4E, 6E, 8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoyl)-1,3-dicyclohexylurea, a side product in the synthesis of succinimidyl all-trans-retinoate, is reported; Hirshfeld surface analysis was employed to identify intermolecular interactions.[Figure not available: see fulltext.].
- Kalantzi, Stefania,Nastopoulos, Vassilios,Papaioannou, Dionissios,Vachlioti, Eleanna
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- Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
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Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
- Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
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- Synthesis of octadecylamine-retinoic acid conjugate for enhanced cytotoxic effects of 5-FU using LDL targeted nanostructured lipid carriers
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The aim of the present study was to reduce 5-FU side effects by targeted nanostructured lipid carriers (NLCs) to LDL receptors that are over expressed in colorectal carcinoma and also use of a new synthesized conjugate of retinoic acid as a cytotoxic agent. Fatty acyl amide derivative of retinoic acid was synthesized by its conjugation to octadecylamine with the expectation to improve its loading capacity in NLCs of 5-FU. The NLCs were prepared by an emulsification-solvent evaporation method using cholesterol and cholesteryl stearate. Physical properties and drug release were studied in NLCs. The cytotoxicity of NLCs loaded with 5-FU and retinoic acid conjugate was studied on colon cancer cells (HT29) using MTT assay. To confirm that drug targeting has been done through LDL receptors, APO-E was omitted from the cell culture and the MTT assay was repeated. FTIR and 1H NMR spectra confirmed successful production of the conjugate. Results showed the IC50 of free 5-FU was about 7.6 μM while in comparable concentration, the cytotoxicity of 5-FU loaded in NLCs containing the retinoic acid conjugate was nearly 2 fold of NLCs just loaded with 5-FU and more than 5 fold of free 5-FU. The retinoic acid conjugate loaded NLCs prepared by cholesterol can target LDL receptors of HT29 cells and seems promising in reducing 5-FU dose in colorectal cancer.
- Varshosaz, Jaleh,Hassanzadeh, Farshid,Sadeghi, Hojjat,Andalib, Sare
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experimental part
p. 429 - 438
(2012/09/25)
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- TRACEABLE RETINOID ACID FOR IMAGING, DISEASE PREVENTION AND THERAPY
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The present invention provides nonradioactive NIR optical imaging agents based up on the structure of retinoid acid derivatives. The nonradioactive NIR optical imaging agent has been evaluated at the cellular level by confocal microscopy, and in vivo in a
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Page/Page column 10
(2012/10/08)
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- Preparation of spermine conjugates with acidic retinoids with potent ribonuclease P inhibitory activity
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Novel mono- and diacylated spermines, readily obtained using isolable succinimidyl active esters of acidic retinoids for the selective acylation of free spermine or in situ activated acidic retinoids for acylating selectively protected spermine followed b
- Magoulas, George,Papaioannou, Dionysios,Papadimou, Evangelia,Drainas, Denis
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experimental part
p. 2689 - 2695
(2009/10/02)
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- Effect of conjugates of all-trans-retinoic acid and shorter polyene chain analogues with amino acids on prostate cancer cell growth
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In the present work, a series of conjugates of amino acids with all-trans-retinoic acid (ATRA) and shorter polyene chain analogues were rationally designed, synthesized by coupling the succinimidyl active esters of the acidic retinoids with appropriately
- Sadikoglou, Eldem,Magoulas, George,Theodoropoulou, Christina,Athanassopoulos, Constantinos M.,Giannopoulou, Efstathia,Theodorakopoulou, Olga,Drainas, Denis,Papaioannou, Dionysios,Papadimitriou, Evangelia
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scheme or table
p. 3175 - 3187
(2009/12/04)
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