A wide set of 264 compounds has been semisynthesized with high yields and purities. These compounds have been obtained through easy synthetic processes based on a solid-phase combinatorial methodology. All the members of this library have one central core of a natural pentacyclic triterpene (oleanolic or maslinic acid) and differ by 6 amino acids, coupled with the carboxyl group at C-28 of the triterpenoid skeleton, and by 10 different acyl groups attached to the hydroxyl groups of the A-ring of these molecules. According to the literature on the outstanding and promising pharmacological activities of other similar terpene derivatives, some of these compounds have been tested for their cytotoxic effects on the proliferation of three cancer cell lines: B16-F10, HT29, and Hep G2. In general, we have found that around 70% of the compounds tested show cytotoxicity in all three of the cell lines selected; around 60% of the cytotoxic compounds are more effective than their corresponding precursors, that is, oleanolic (OA) or maslinic (MA) acids; and nearly 50% of the cytotoxic derivatives have IC50 values between 2- to 320-fold lower than their corresponding precursor (OA or MA).
We have studied the nucleic acid concentrations and protein turnover rates, fractional protein synthesis (KS), degradation (KD), and accumulation (KG) rates, synthesis capacity (CS), synthesis efficiency (KRNA), synthesis per DNA unit (KDNA), and protein retention efficiency (PRE) in the liver of rainbow trout (Oncorhynchus mykiss) at different stages of development (fingerling: 7 g; juvenile: 45, 65, and 170 g; adult: 420 g; represented by 14-, 24-, 28-, 40-, and 96-week-old fish). Our results show that liver growth is characterized by linear increases in both total DNA (reflecting hyperplasia) and the protein:DNA ratio (reflecting hypertrophy); hyperplasia was more pronounced than hypertrophy. Development was accompanied by a significant decrease in KS, while KGdid not change significantly. There was a concomitant fall in RNA concentration measured as milligrams per gram of protein (CS) and as milligrams per gram of liver, while KRNAonly decreased slightly. The alterations in KSwere thus probably due to a decrease in CS. The pronounced fall in KStogether with the slight increase in the protein:DNA ratio may be responsible for the decline in KDNA. PRE increased concomitantly with an increase in whole-body weight.
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