Release studies of the anticancer drug 5-fluorouracil from chitosan-banana peel extract films.

5-F-lourouracil is an anticancer drug used for the treatment of different types of cancers. 5-flourouracil loaded chitosan-banana peel extract films were prepared for the in vitro drug release studies. Solvent casting technique was employed to prepare the films. The structure and morphology of the prepared films were analysed by FTIR, XRD and SEM methods and confirmed the presence of drug in the films. The drug loaded films show excellent thermal stability and good shelf life. Studies revealed that the percentage of banana peel extract influences the swelling properties of the film, thickness of the films and release of the drug from the films. Increase in the concentration of chitosan and banana peel extract decreases the swelling properties of the film and rate of release of the drug from the film. The release rate of 5-fluorouracil from the drug loaded chitosan-banana peel extract films were followed spectrophotometrically at λmax 266 nm and the film derived from 1 % chitosan solution and 1 mL aqueous banana peel extract (saturated) exhibited maximum drug release. Cytotoxicity studies proved that the films are non-toxic in nature and augurs well for their applications as excellent drug delivery systems. Antimicrobial studies show that the drug loaded chitosan-banana peel extract films were found to be active against microbes E. coli, Streptococcus mutans, Staphylococcus aureus, Candida albicans and Aspergillus niger and inactive against Pseudomonas aeruginosa.

Advances in the Solid-Phase Synthesis of Pyrimidine Derivatives.

This Review describes the existing synthetic approaches for the solid-phase synthesis (SPS) of differently substituted and fused pyrimidine derivatives. These synthetic strategies are classified on the basis of the different synthetic routes leading to the particular type of pyrimidine heterocycle formed. The Review discusses the application of a variety of polystyrene derived supports for the construction of pyrimidine rings. The effect of microwave heating on the solid-phase synthesis is also addressed in the review.

Transition state analogue imprinted polymers as artificial amidases for amino acid p-nitroanilides: morphological effects of polymer network on catalytic efficiency.

The morphology of the polymer network - porous/less porous - plays predominant role in the amidase activities of the polymer catalysts in the hydrolytic reactions of amino acid p-nitroanilides. Polymers with the imprints of stable phosphonate analogue of the intermediate of hydrolytic reactions were synthesized as enzyme mimics. Molecular imprinting was carried out in thermodynamically stable porogen dimethyl sulphoxide and unstable porogen chloroform, to investigate the morphological effects of polymers on catalytic amidolysis. It was found that the medium of polymerization has vital influence in the amidase activities of the enzyme mimics. The morphological studies of the polymer catalysts were carried out by scanning electron microscopy and Bruner-Emmett-Teller analysis. The morphology of the polymer catalysts and their amidase activities are found to be dependent on the composition of reaction medium. The polymer catalyst prepared in dimethyl sulphoxide is observed to be efficient in 1:9 acetonitrile (ACN)-Tris HCl buffer and that prepared in chloroform is noticed to be stereo specifically and shape-selectively effective in 9:1 ACN-Tris HCl buffer. The solvent memory effect in catalytic amidolysis was investigated using the polymer prepared in acetonitrile.

Catalytic amidolysis of amino acid p-nitroanilides using transition state analogue imprinted artificial enzymes: Cooperative effect of pyridine moiety.

Enzyme-like polymer catalysts with the imprints of phosphonate transition state analogue (TSA) lined along with imidazole and pyridine moieties were synthesized using methacryloyl-l-histidine and 4-vinylpyridine as the functional monomers and phenyl-1-(N-benzyloxycarbonylamino)-2-(phenyl)ethyl phosphonate - the TSA of hydrolytic reaction as the template for the amidolysis of N-benzyloxycarbonyl-l-phenylalanine p-nitroanilide (Z-l-Phe-PNA). Polymers containing different functional groups can act together to provide catalytic activity and selectivity superior to what can be obtained from monofunctional analogues. The higher rate acceleration exhibited by the bifunctional polymer over the monofunctional polymers indicates cooperative catalysis of imidazole and pyridine moieties. The optimum catalytic competence is shown by the bifunctional polymer containing imidazole and pyridine moieties in 2:1M ratio which may be due to alignment of the functional groups in proper H-bond distance. In addition to the non-covalent interactions like hydrogen bonding or π-stacking interactions between the functional groups of the polymer and the template, 3D-microcavities complementary to the geometry of the template are necessary for effective shape selective binding. Michaelis-Menten kinetics implies that only the catalysts with imidazole moieties act as enzyme-like catalysts and imidazole is the key catalytic function of the enzyme mimics.

Conformation of an octapeptide fragment (2-9) of kaliocin-1 in DMSO-d6 by 1H NMR and restrained molecular dynamics.

Kaliocin-1, a 31-residue synthetic peptide (FFSASCVPGADKGQFPNLCRLCA GTGENKCA), which has shown the antimicrobial activity forms the 152-182 fragment of human lactoferrin (HLf). As the octapeptide FSASCVPG forms the 2-9 fragment of kaliocin-1, in the present study, its conformation in dimethyl sulfoxide-d6 (DMSO-d6) has been determined using two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy as well as restrained molecular dynamics. Sequence specific assignments of all the 1H resonances have been carried out using 2D correlation experiments (2D DQF-COSY, TOCSY and ROESY). In dimethyl sulfoxide-d6 at 25 degrees C, the octapeptide adopts a predominantly extended backbone conformation. The calculated structure resembles closely with the reported structure of the corresponding fragment of HLf. The peptide also has sequence and structural similarity with the corresponding fragments of lactoferrins from other organisms.

Conformational analysis of sea cucumber (Caudina arenicola) C globin 94-97 fragment, Pro-Glu-Leu-Leu.

The tetrapeptide Pro-Glu-Leu-Leu forms the 94-97 fragment of C globin in sea cucumber. 2% Butanediol dimethacrylate-cross linked polystyrene (2% BDDMA-PS), which had been optimized, was used for the synthesis of the tetrapeptide Pro-Glu-Leu-Leu. The peptide was synthesized by using Boc-amino acid strategy. The peptide purity was checked by RP-HPLC and the peptide was characterized by (1)H NMR spectroscopy and amino acid analysis. Conformation of the peptide was studied by 1D- and 2D- homonuclear (1)H NMR, in DMSO-d6 at 300K. The conformation of the synthetic tetrapeptide (extended backbone conformation) is not in agreement with that in C globin.

Solid phase synthesis of hydrophobic difficult sequence peptides on BDDMA-PS support.

This article illustrates the successful and efficient solid phase assembly of hydrophobic difficult sequence peptides following both t-Boc and Fmoc chemistry. The peptides were synthesized on an optimized 1,4-butanediol dimethacrylate-crosslinked polystyrene support (BDDMA-PS). Four difficult sequence test peptides, VAVAG, VIVIG, QVGQVELG and VQAAIDYING, were synthesized in relatively good yield and purity without any aggregation problems. The peptides were assembled on chloromethylated and 4-hydroxymethylphenoxymethyl (HMP) BDDMA-PS resins. The peptides were fabricated using Boc amino acid 1-hydroxybenzotriazolyl and Fmoc amino acid pentafluorophenyl active esters in coupling reactions. The peptides after synthesis were cleaved from the polymeric support by exposing the peptidyl resin to 90% trifluroacetic acid/5% thioanisole/5% EDT mixture. The HPLC and MALDI TOF MS studies of the peptides revealed the high homogeneity of the synthesized peptides. Chloromethylated resin having a functional group loading of 1.14 mmol Cl/g was used for the synthesis. The yield and homogeneity of these peptides synthesized using the new support were high when compared with the conventional DVB-PS resin.