Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives.

A new series of theophylline containing acetylene derivatives (6a-6b and 7-13) and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives (20-32) have been designed and synthesized. These compounds were screened for anticancer and antimicrobial activity. Further the computational docking and 2D QSAR were performed using MOE software to identify novel scaffolds. The results showed that compound 29 and 30 exhibit significant cytotoxic effect on all four cancer cells such as lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375) with IC50 values of 2.56, 2.19, 1.89, 4.89 µM and 3.57, 2.90, 2.10, 5.81 µM respectively. Whereas quite different results were observed for these compounds in antimicrobial studies. Compounds 11, 21 and 26 have exhibited significant minimum inhibitory concentrations (MIC) against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The docking studies demonstrate that compound 27, 28, 29 and 30 have good dock score and binding affinities with various therapeutic targets in cancer cell proliferation. In addition these compounds have shown acceptable correlation with bioassay results in the regression plots generated in 2D QSAR models. This is the first report to demonstrate the theophylline containing acetylene derivatives and theophylline containing 1,2,3-triazole nucleoside hybrids as potential anticancer and antimicrobial agents with comprehensive in silico analysis.

Optimization of parameters for enhanced oil recovery from enzyme treated wild apricot kernels.

Present investigation was undertaken with the overall objective of optimizing the enzymatic parameters i.e. moisture content during hydrolysis, enzyme concentration, enzyme ratio and incubation period on wild apricot kernel processing for better oil extractability and increased oil recovery. Response surface methodology was adopted in the experimental design. A central composite rotatable design of four variables at five levels was chosen. The parameters and their range for the experiments were moisture content during hydrolysis (20-32%, w.b.), enzyme concentration (12-16% v/w of sample), combination of pectolytic and cellulolytic enzyme i.e. enzyme ratio (30:70-70:30) and incubation period (12-16 h). Aspergillus foetidus and Trichoderma viride was used for production of crude enzyme i.e. pectolytic and cellulolytic enzyme respectively. A complete second order model for increased oil recovery as the function of enzymatic parameters fitted the data well. The best fit model for oil recovery was also developed. The effect of various parameters on increased oil recovery was determined at linear, quadric and interaction level. The increased oil recovery ranged from 0.14 to 2.53%. The corresponding conditions for maximum oil recovery were 23% (w.b.), 15 v/w of the sample, 60:40 (pectolytic:cellulolytic), 13 h. Results of the study indicated that incubation period during enzymatic hydrolysis is the most important factor affecting oil yield followed by enzyme ratio, moisture content and enzyme concentration in the decreasing order. Enzyme ratio, incubation period and moisture content had insignificant effect on oil recovery. Second order model for increased oil recovery as a function of enzymatic hydrolysis parameters predicted the data adequately.

Influence of processing parameters on textural characteristics and overall acceptability of millet enriched biscuits using response surface methodology.

Five blends of refined wheat flour (RWF) (63.2 - 96.8, %RWF) and millet were used to manufacture biscuits baked for varying time (3.3-6.7 min) and temperature (166.6 - 183.4 °C). The manufactured biscuits were evaluated in terms of textural attributes (crispness, hardness and cutting strength) and overall acceptability (OAA). Results showed that increasing the amount of RWF in biscuits decreased (p < 0.01) hardness. Prolonging the baking time led to a decrease (p < 0.01) in hardness and cutting strength and a significant increase (p < 0.05) in OAA. Increase in baking temperature was followed by an increase in crispness (p < 0.01) and OAA (p < 0.1), while hardness and cutting strength (p < 0.01) decreased. Optimum processing condition generated form the models was, - blend ratio, 90%RWF; baking time, 6 min and baking temperature, 170 °C. The predicted responses in terms of crispness, hardness, cutting strength and OAA were 45, 0.3N, 27.2N and 8.9, respectively. The desirability of the optimum conditions was 0.98.

Evaluation of the healing potential of Schrebera swietenioides in the dexamethasone-suppressed wound healing in rodents.

The wound healing potential of the aqueous, alcoholic extracts, and the butanolic fraction of the alcoholic extract obtained from the bark of Schrebera swietenioides were evaluated in the dexamethasone suppressed wound healing model. The work was conducted on rodents using incision, excision, and dead space wound models. The extracts of S swietenioides enhanced the breaking strength of incision wounds significantly (P < .05). Faster epithelization and contraction of excision wounds were observed in the treated groups (P < .05). Dead space wound model demonstrated an increase in breaking strength of granulation tissue and weight of dried granulation tissue after treatment with the extracts.The extracts attenuated the effect of dexamethasone on healing.The total RNA isolated from the granulation tissues of the extract-treated animals was significantly higher than in both dexamethasone and normal groups, (P < 0.05). It was observed that the DNA was intact in all the groups. These findings suggest that dexamethasone suppresses wound healing, possibly through an inappropriate transcription rather than causing DNA damage.The S swietenioides extracts have the capacity to reverse this effect.

Regression analysis of total fatty acids from human whole brain according to age and sex.

Total fatty acids processed from whole brain samples removed at autopsy from men and women, 26-87 years of age, were esterified, the methyl esters analyzed by gas chromatography, and the respective profiles deduced. In the study of the effect of age and sex in relation to the fatty acid levels, regression analysis was applied to smoothened data to take care of extraneous effects or variables. Toward this end, five age groupings were formed and the regression relationships explored for each group per sex. Generally, the saturated homologs occurred in higher amounts among males of advancing age but decreased with age among females. This effect stemmed from the even-carbon acids. For the unsaturated fatty acids, the reverse behavior appeared evident. For the prominent acids, 16:0 and 18:0, the differences were moderately significant for cases 50 years and older, for 18:2, significance based on either sex was noted with all age groups.

Effect of feeding coffee and its lipids on regenerating and intact liver.

Liver regeneration was stimulated in partially hepatectomized rats fed diets supplemental with up to 7.0% by weight of ground green and roasted Brazilian or Hawaiian (Kona) coffee in a basal powdered ration but was little influenced by decaffeinated or African Robusta coffee diets over a period of 10 days. The causative agent occurred in the total lipids from the active ground coffee batches and could be concentrated in the unsaponifiable portion as was also noted with the product from Robusta coffee. The lipids were inactive by the sc route. Pressed Brazilian green coffee oil elicited a lower regenerative response and other caffeine sources such as ground kola nuts and Paraquay tea at levels of 7.0% as demonstrated earlier for black tea, were nonstimulatory. Caffeine tended to depress liver regeneration, a level of 0.40% being quite inhibitory. As based on the composition of the unsaponifiable material, the activity might reside in the diterpene alcohol fraction containing cafestol and kahweol and some fractionation of the mixture was attempted currently. The agents which were active in the operated series generally elicited wet and dry liver enlargement in intact rats over the same period.

Total fatty acids of human liver in relation to age, sex and pathology.

Lipids were extracted from 28 "normal", 3 fatty and 2 cirrhotic adult livers removed at necropsy as well as from 4 newborn and infant organs. The total fatty acids were processed, the methyl esters submitted to gas chromatographic analysis and the acid differences ascertained relative to age, sex and pathology. Among other significant findings, the unsaturated acids ranged higher than the saturated homologs and were even greater in the fatty liver lipids. The latter showed an increase in 18:1 and depressions in 18:0, 22:0 and 24:0 as compared to the "normal" specimens and the same changes in 18:0 and 18:1 as contrasted to the cirrhotic lipids.

Distribution of total fatty acids in human splenic lipids.

Lipids were extracted from adult human spleens obtained at surgery or autopsy, 26 with some degree of congestion and 7 displaying congestive splenomegaly. The fatty acids were processed following saponification of the lipids, esterified and the esters as such as well as hydrogenated aliquots analyzed by gas chromatography. The significance of fatty acid differences on the basis of age, sex, pathology and mode of organ acquisition was determined by t-tests. Several acid differences were significant in regard to age groups, between congestion and splenomegaly (surgical, autopsy and overall) and in the comparison of the respective surgical vs autopsy groups. No definite difference could be attributed to sex.

Kidney total fatty acids in renal cell carcinoma and infection.

Lipids extracted from the kidneys of adults with renal cell carcinoma or infection after careful dissection of lesions and from organs showing minimal alterations were saponified and the fatty acids converted to the methyl esters. Gas chromatographic criteria were applied to the esters as such and to hydrogenated aliquots, and the relative percentages of the component acids were ascertained. The various lipid classes were well represented in the total fatty acid mixtures. The unsaturated acids ranged higher than the saturated homologs. Comparisons of the fatty acids were carried out on the basis of age, sex, kidney position, mode of ascquisition (surgery and autopsy), and pathology. Several small but statistically significant differences were discerned according to the categories but with few exceptions, these involved acids occurring at low levels and with wide variance.