Current Bioactive Compounds - Volume 10, Issue 4, 2014

The exploitation of the antitumor properties of fungal secondary metabolites is one of the fundamental objectives pursued by a multiplicity of research groups and laboratories working on the characterization of natural products worldwide. The availability of a synthetic framework on such a vast interdisciplinary topic can enhance the current knowledge by supporting novel findings, and stimulating further insights. This paper offers an overview of the state-of-the-art concerning this category of compounds and their occurrence, selection, structural diversity and mechanisms of action on tumor cells.

A simple and sensitive red spectrofluorimetric method has been described for the estimation of hypocrellin B in rabbit plasma and ocular tissues such as retina, iris, aqueous humour and vitreous body. The fluorimetric estimation was achieved using black coloured 96- well plate at an excitation/emission wavelengths of 470/620 nm with a specific well volume of 100 µL/well. Hypocrellin B calibration curves were linear at a concentration ranging from 20 ng/mL to 1280 ng/mL with correlation coefficient between 0.86 and 0.99 in ocular tissues and plasma. Limit of detection and quantification was between 0.011 to 0.017 µg/mL and 0.034 to 0.054 µg/mL respectively for hypocrellin B in different ocular tissues and plasma. The percentage relative standard deviation observed for the validation parameters such as method precision, system precision, intra- inter day, analyst to analyst variations and robustness is found to be less than 12.5 % for the observed fluorescence intensity in different ocular tissues/plasma. The method has been applied to check the hypocrellin B concentration in plasma and ocular tissues after intravenous administration and found that hypocrellin B has some exposure to the posterior segment of eye without major intraocular presuure abnormalities. This selective and sensitive fluorimetric method will facilitate the future investigations of hypocrellin B on ocular delivery of hypocrellin B with less solvent consumption.

Alzheimer’s disease (AD), a progressive neurodegenerative disease has become one of the major health issues in developed countries. Continuing our research on biological activity of coumarin derivatives, this study presents evaluation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity of series 4- methylcoumarins. All studied compounds showed inhibitory activity in a similar manner as they are capable of scavenging reactive oxygen species and reducing transition metals. This study was focused on structural features that regulate biological activity of 4-methylcoumarins.

Three series of novel bile acid conjugates with different α–amino acid have been synthesized. The synthesis of final compounds was accomplished with anhydride using ethyl chloroformate. The conjugation was introduced via coupling of the bile acid anhydride with appropriately functionalized α-amino acid. Biological evaluation of synthesized compounds was carried out in vitro for their antimicrobial and antifungal properties against human pathogens. The bile acid conjugates 1g, 2g, 2h and 3g indicated 2–fold stronger antimicrobial activity compared to ciprofloxacin. The final products were obtained in both high yield and purity. The prepared conjugated bile acids were characterized by mass spectrometry, infrared spectroscopy and nuclear magnetic resonance proton spectroscopy which are also discussed along with the thin–layer chromatographic properties.

The optimization and kinetic of rosmarinic acid extraction from Orthosiphon stamineus were investigated in this study. In the preliminary study, the extractions were carried out to identify the optimal ethanol concentration. Then, the optimal ethanol concentration was used to optimize the extraction variables (solventto- solid loading ratio, temperature and time) by central composite design. The optimum conditions for the rosmarinic acid extraction were at the concentration of ethanol, 70% v/v; solvent-to-solid loading ratio, 9.14; extraction temperature, 56.53°C; and extraction time, 3 hours. Subsequently, this study used six proposed models to describe the kinetic of the rosmarinic acid extraction. Two-site kinetic model gave the best fit for the experimental data with the highest coefficient of determination, R2 (0.976) and the smallest values of root mean square error (RMSE) (1.522). The goodness of fit is due to the presence of the rate constants of both fast and slow released fractions in the model. Hence, two-site kinetic model is the most appropriate model to describe the rosmarinic acid extraction from O. stamineus in a reflux extraction system.

Benzazolo[3,2-a]quinolium salts (BQS) are cationic quaternary alkaloids with similar structure to the anticancer agent ellipticine. This study describes the synthesis and screen, at the experimental concentration of 10 mM, utilizing the 60 cell line anti-cancer screening of two BQS, namely, 7-benzyl-3- aminobenzimidazo[3,2-a]quinolinium chloride (ABQ-48: NSC D-763307) and the corresponding 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium chloride (NBQ 48: NSC D-763303). Compound ABQ-48: NSC D-763307 was also screened in the 5-dose NCI panel. These compounds differ in the presence of an amino or nitro substituent at the 3- position in ring A. The data show that ABQ 48 with electron donating amino group at position 3 in ring A is highly effective in the growth inhibition in several cancer cell lines. However, its analog NBQ 48 which has an electron withdrawing nitrogen group at this position has negligible effect in most of the cell lines. In particular, ABQ 48 shows >90% growth inhibition in KM12, U251 & SK-MEL-5; and >70% growth inhibition in several cell lines. As per the NCI’s screening criteria ABQ 48 showed better than 60% growth inhibition in at least eight tumor cell lines, and thus, selected for the five dose response study. It is therefore concluded that the biological activity of these compounds is greatly affected by their electron donating properties. Additionally, this work describes the complete proton and carbon-13 chemical shifts assignments using 1D and 2D nuclear magnetic resonance techniques.

In the present investigation an attempt was made to screen actinomycetes for the therapeutic lead. Marine soil samples were collected from Chennai region, Tamil Nadu, India for the isolation of actinomycetes, about 6 actinobacterial colonies were isolated and screened for its bioactive potential by cross streak method. Among the six isolates screened, one isolate named VITSD1showed potent bioactivity. The molecular analysis of the isolate based on 16S r-DNA gene sequence was validated by existing taxonomic reports. The strain VITSD1 was found 100 % similar to Streptomyces gancidicus. The VITSD1 crude extract checked for antibiogram at 5mg/mL against clinical pathogens was found to have maximum antibacterial activity against Escherichia coli (30±0.92mm), Pseudomonas aeruginosa (28±0.93mm), Salmonella typhi (18±0.98mm) and Staphylococcus aureus (20±1.02mm). The antioxidant potential of the strain showed maximum inhibition at 5.0mg/mL concentration with 65±1.94 %. Hence the present study justifies the overwhelming circumstantial evidence as the most bioactive metabolites are from actinomycetes which are of marine origin.