Limonoids from the Branches and Leaves of Aglaia lawii and Their Cytotoxic Activities.

Three undescribed limonoids (1-3), named aglaians G-I, and one new natural product azedaralide (4), together with nine known analogues (5-13) were isolated from the branches and leaves of Aglaia lawii by RP C18 column, silica gel column, Sephadex LH-20 column chromatography and preparative HPLC. The structures of the new compounds were elucidated by IR, HRESIMS, 1D, 2D NMR, electronic circular dichroism (ECD) calculations and X-ray crystallography diffraction analysis. The results of bioassay showed that the compound 12 exhibited potential inhibitory activity against six human tumor cell lines (MDA-MB-231, MCF-7, Ln-cap, A549, HeLa and HepG-2) with IC50 values as 8.0-18.6 µM.

Unusual triterpenoids and steroids from Cipadessa baccifera and their biological activities.

Five undescribed triterpenoids and steroids (1-5), as well as ten known compounds, were purified from the branches and leaves of Cipadessa baccifera. Notably, 1 and 2 are rare cipadesin-type limonoids with an unusual 8,30-epoxide ring and 1,8-ether linkage, respectively. Compound 5 possessed pregnane steroid skeleton with an uncommon 5/6/6/6/5-fused ring system. Their structures were constructed by extensive spectroscopic analysis (NMR, IR, UV, and HRESIMS), and their absolute configurations were confirmed by ECD calculations and quantum chemical calculations. All the isolates were in vitro assayed for their antimicrobial potentials against 6 pathogenic microorganisms and antiproliferation activities against five human cancer cell lines. As a result, compounds 5, 12, 13, and 14 exhibited moderate antibacterial activities (MIC: 25-50 µg/mL). Moreover, 5 showed cytotoxicity against five cancer cell lines with IC50 values ranging from 8.0 to 19.9 µM.

A novel class of C14-sulfonate-tetrandrine derivatives as potential chemotherapeutic agents for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most common malignancy of the liver, exhibits high recurrence and metastasis. Structural modifications of natural products are crucial resources of antitumor drugs. This study aimed to synthesize C-14 derivatives of tetrandrine and evaluate their effects on HCC. Forty C-14 sulfonate tetrandrine derivatives were synthesized and their in vitro antiproliferative was evaluated against four hepatoma (HepG-2, SMMC-7721, QGY-7701, and SK-Hep-1) cell lines. For all tested cells, most of the modified compounds were more active than the lead compound, tetrandrine. In particular, 14-O-(5-chlorothiophene-2-sulfonyl)-tetrandrine (33) exhibited the strongest antiproliferative effect, with half-maximal inhibitory concentration values of 1.65, 2.89, 1.77, and 2.41 µM for the four hepatoma cell lines, respectively. Moreover, 33 was found to induce apoptosis via a mitochondria-mediated intrinsic pathway via flow cytometry and western blotting analysis. In addition, colony formation, wound healing, and transwell assays demonstrated that 33 significantly inhibited HepG-2 and SMMC-7721 cell proliferation, migration, and invasion, indicating that it might potentially be a candidate for an anti-HCC therapy in the future.

Synthesis of piscidinol A derivatives and their ability to inhibit HIV-1 protease.

Four types of piscidinol A derivatives were synthesized and evaluated their ability to inhibit HIV-1 protease to understand their structure-activity relationships. Of these tirucallane-type triterpene derivatives, an A-seco derivative (1b) moderately inhibited human immunodeficiency virus (HIV) protease (IC50 38.2 µM). The 2,2-dimethyl succinic acid (DMS) acylated tirucallane derivatives (4b, 6a, and 7b, 50 < IC50 < 100 µM) were more inhibitory against HIV-1 PR than the others (PA, 2a, 4a, 4c-4d, 5a, 6b-6d, and 7a, IC50 > 100 µM). These findings indicated that the 2,3-seco-2,3-dioic acid (1b) and DMS-acylated tirucallane-type derivatives preferably inhibited HIV viral protease.