Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives.

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51-53.33 µM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC50 for AChE = 0.82 ± 0.08 µmol•L-1, IC50 for BuChE = 46.30 ± 3.26 µmol•L-1) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC50 for AChE = 10.54 ± 0.86 µmol•L-1, IC50 for BuChE = 0.26 ± 0.08 µmol•L-1). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.

Synthesis of Icaritin and ß-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines.

BACKGROUND: Prenyl flavonoid icaritin (1) and ß-anhydroicaritin (2) are two natural products with important biological and pharmacological effects. such as antiosteoporosis, estrogen regulation and antitumor properties. OBJECTIVE: The present study investigates the synthesis and cytotoxic activities on three Human cancer cell lines (Hela, HCC1954 and SK-OV-3) of icaritin and ß-anhydroicaritin Mannich base derivatives in vitro models. METHOD: Preylated flavonoid icaritin (1) upon treatment with formic acid under microwave assistance gave another natural product ß-anhydroicaritin (2) in good yield (89%). Based on Mannich reaction of 1 or 2 with various secondary amines and formaldehyde, two series eighteen new 6-aminomethylated flavonoids Mannich base derivatives 3-11 and 12-20 were synthesized. Their cytotoxic potential against three human cancer cell lines (Hela, HCC1954 and SK-OV-3) were evaluated by the standard MTT method with cis-Platin and Paclitaxel as positive control. RESULTS: Our research showed that most of these flavonoid Mannich base derivatives displayed equal or higher (lower IC50 values) cytotoxic activities than the positive control cis-Platin. Some compounds possess the IC50 value below 10µM. Compounds 6-(diisopropylamino)methyl- and 6-morpholinylmethyl substituted ß-anhydroicaritin (15 and 19) showed selective cytotoxicity against HCC1954 cells (IC50 12.688 µM) and Hela cells (IC50 6.543 µM) respectively. CONCLUSION: Our finding most of icaritin and ß-anhydroicaritin Mannich base derivatives possessing moderate to potent cytotoxicity against these three cancer cells (Hela, HCC1954 and SK-OV-3). Compound 15 and 19 showed selective cytotoxicity against HCC1954 cells and Hela cells respectively, they are potential and selective anticancer agent and worthy of further development.

Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 µM than the positive control cis-platin (IC50 41.25 µM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 µM than the positive control cis-platin (IC50 29.68 µM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 µM than the positive control cis-platin (IC50 21.27 µM).

Three new vibralactone-related compounds from cultures of Basidiomycete Boreostereum vibrans.

Three new compounds, named as vibralactones K-M (1-3), together with vibralactone (4) have been isolated from cultures of the Basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic evidences (1D and 2D NMR, HRMS, UV, and IR data), chemical methods and literature data. None of the compounds was cytotoxic against five human cancer cell lines and showed inhibitory activity on the pancreatic lipase.

Three new compounds from the cultures of basidiomycete Boreostereum vibrans.

Three new compounds, vibranether (1), myrrhlalkyldiol (2), vibralactone H (3), together with three known compounds, 2-methyl-6-p-tolylheptane-2,3-diol (4), 2-hydroxy-2-methyl-6-p-tolylheptan-3-one (5), and vibralactone (6), were isolated from the cultures of the basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic evidences (1D and 2D NMR, HRMS, UV, and IR data), chemical methods, and the literature data. The new compounds displayed no significant cytotoxicities against five human cancer cell lines (IC50>40 µM).

Synthesis and cytotoxicity of chalcones and 5-deoxyflavonoids.

Chalcones 1~8 and 5-deoxyflavonoids 9~22 were synthesized in good yields by aldol condensation, Algar-Flynn-Oyamada reaction, glycosidation, and deacetylation reaction, respectively, starting from 2-acetyl phenols substituted by methoxy or methoxymethoxy group and appropriately benzaldehydes substituted by methoxy, methoxymethoxy group, or chlorine. Among them, 13 and 17~22 are new compounds. The cytotoxicity bioassays of these chalcones and 5-deoxyflavonoids were screened using the sulforhodamine B (SRB) protein staining method, and the results showed that compounds 2, 4, 5, 6, 10, 15, and 19 exhibited moderate cytotoxicity against the cancer cell line of MDA-MB-231, U251, BGC-823, and B16 in comparison with control drugs (HCPT, Vincristine, and Taxol).