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In search of new cytotoxic derivatives based on the lupane scaffold, methyl betulonate and methyl 20,29-dihydrobetulonate were conjugated with Reformatsky reagents to provide homolupanes extended at the C3-carbon atom. Further transformations of the functional groups afforded a series of derivatives with 2-hydroxyethyl and allyl alcohol moieties. Their varying antiproliferative activity in vitro was then investigated in four cancer cell lines and in normal human BJ fibroblasts. In cervical carcinoma HeLa cells, derivatives 5, 6 and 17 were the most promising with lower micromolar IC

Background: Oleanolic acid is a natural plant adaptogen, and tryptamine is a natural psychoactive drug. To compare their effects of with the effect of their derivatives, tryptamine and fluorotryptamine amides of oleanolic acid were designed and synthesized. Methods: The target amides were investigated for their pharmacological effect, and basic supramolecular self-assembly characteristics. Four human cancer cell lines were involved in the screening tests performed by standard methods. Results: The ability to display cytotoxicity and to cause selective cell apoptosis in human cervical carcinoma and in human malignant melanoma was seen with the three most active compounds of the prepared series of compounds. Tryptamine amide of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (3a) exhibited cytotoxicity in HeLa cancer cell lines (IC50 = 8.7 ± 0.4 µM) and in G-361 cancer cell lines (IC50 = 9.0 ± 0.4 µM). Fluorotryptamine amides of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (compounds 3b and 3c) showed cytotoxicity in the HeLa cancer cell line (IC50 = 6.7 ± 0.4 µM and 12.2 ± 4.7 µM, respectively). The fluorotryptamine amide of oleanolic acid (compound 4c) displayed cytotoxicity in the MCF7 cancer cell line (IC50 = 13.5 ± 3.3 µM). Based on the preliminary UV spectra measured in methanol/water mixtures, the compounds 3a–3c were also found to self-assemble into supramolecular systems. Conclusions: An effect of the fluorine atom present in the molecules on self-assembly was observed with 3b. Enhanced cytotoxicity has been achieved in 3a–4c in comparison with the effect of the parent oleanolic acid (1) and tryptamine. The compounds 3a–3c showed a strong induction of apoptosis in HeLa and G-361 cells after 24 h.

Six new (1, 2, 6, 8, 13, and 20) and twenty previously isolated (3&ndash, 5, 7, 9&ndash, 12, 14&ndash, 19, and 21&ndash, 26) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral Sinularia polydactyla collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds 3&ndash, 7, 9&ndash, 20, and 22&ndash, 26, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids 22 and 23 showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds 11, 12, 22, and 23 at 20 &micro, M. The results of the androgen receptor (AR) reporter assay showed that compound 11 exhibited the strongest inhibition of AR at 10 &micro, M, while it is noteworthy that steroids 10, 16, and 20 displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds 11 and 23 showed neuroprotective activity on neuron-like SH-SY5Y cells.

In search of new cytotoxic derivatives based on the lupane scaffold, the seco-lupane azides were coupled with a number of alkynes under the 1,3-dipolar cycloaddition (CuAAC) conditions to afford 1,2,3-triazoles. Phenylalkynes having different substituents at the para position were used as starting materials. Similarly, coupling of the seco-lupane thiocyanate with sodium azide gave 5-thiotetrazole. The cytotoxicity of thirteen derivatives were investigated, as well as the effect of substituents in the phenyl ring on the activity of 1,2,3-triazoles. Limited activity was observed for some of these products. Most of the studied compounds were inactive in cancer cell lines and healthy fibroblasts. Triazole 46 exhibited cytotoxic activity against CEM and MCF-7 cancer cell lines, however, it was also toxic to normal human BJ fibroblasts. Two other derivatives – triazole 45 and tetrazole 49 – exhibited low cytotoxicity. Compound 49 showed good selectivity towards tumor cell lines compared to normal fibroblasts. This compound did not affect the growth of normal human fibroblasts and therefore has a wide therapeutic window.