Clerodane diterpenes: sources, structures, and biological activities

The clerodane diterpenoids are a widespread class of secondary metabolites and have been found in several hundreds of plant species from various families and in organisms from other taxonomic groups

Recent advances in the investigation of curcuminoids

More than 30 Curcuma species (Zingiberaceae) are found in Asia, where the rhizomes of these plants are used as both food and medicine, such as in traditional Chinese medicine. The plants are usually aromatic and carminative, and are used to treat indigestion, hepatitis, jaundice, diabetes, atherosclerosis and bacterial infections. Among the Curcuma species, C. longa, C. aromatica and C. xanthorrhiza are popular. The main constituents of Curcuma species are curcuminoids and bisabolane-type sesquiterpenes. Curcumin is the most important constituent among natural curcuminoids found in these plants. Published research has described the biological effects and chemistry of curcumin. Curcumin derivatives have been evaluated for bioactivity and structure-activity relationships (SAR). In this article, we review the literature between 1976 and mid-2008 on the anti-inflammatory, anti-oxidant, anti-HIV, chemopreventive and anti-prostate cancer effects of curcuminoids. Recent studies on curcuminoids, particularly on curcumin, have discovered not only much on the therapeutic activities, but also on mechanisms of molecular biological action and major genomic effects

HIV entry inhibitors and their potential in HIV therapy

This review discusses recent progress in the development of anti-HIV agents targeting the viral entry process. The three main classes (attachment inhibitors, co-receptor binding inhibitors, and fusion inhibitors) are further broken down by specific mechanism of action and structure. Many of these inhibitors are in advanced clinical trials, including the HIV maturation inhibitor bevirimat, from the authors’ laboratories. In addition, the CCR5 inhibitor maraviroc has recently been FDA-approved. Possible roles for these agents in anti-HIV therapy, including treatment of virus resistant to current drugs, are also discussed

Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents

This article reviews the antitumor and anti-HIV activities of naturally occurring triterpenoids, including the lupane, ursane, oleanane, lanostane, dammarane, and miscellaneous scaffolds. Structure–activity relationships of selected natural compounds and their synthetic derivatives are also discussed

Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity

Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds

Cytotoxic esterified diterpenoid alkaloid derivatives with increase selectivity against a drug-resistant cancer cell line

C-6 Esterifications of delpheline (1) were carried out to provide 20 new diterpenoid alkaloid derivatives (4–22, 24). Three natural alkaloids (1–3) and all synthesized compounds (4–25) were evaluated for cytotoxic activity against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines and interestingly, showed an improved drug resistance profile compared to paclitaxel. Particularly, 6-(4-fluoro-3-methylbenzoyl)delpheline (22) displayed 2.6-fold greater potency against KB-VIN cells compared with the parental non-drug resistant KB cells. 6-Acylation of 1 appears to be critical for producing cytotoxic activity in this alkaloid class and a means to provide promising new leads for further development into antitumor agents

Carolignans from the Aerial Parts of Euphorbia sikkimensis and Their Anti-HIV Activity

Seven new carolignans, including two pairs of enantiomers (±)-erythro-7′-methylcarolignan E (1a/1b) and (±)-threo-7′-methylcarolignan E (2a/2b), (+)-threo-carolignan E (3a), (+)-erythro-carolignan E (4a), and (−)-erythro-carolignan Z (5), together with four known lignans (3b, 4b, 6, and 7) and six polyphenols (8–13) were isolated from the aerial parts of Euphorbia sikkimensis. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Seven of the isolates were examined for anti-HIV effects, and compounds 1a and 1b showed moderate anti-HIV activity with EC50 values of 6.3 and 5.3 μM

Songaricalarins A–E, Cytotoxic Oplopane Sesquiterpenes from Ligularia songarica

Five new highly oxygenated oplopane sesquiterpenes, songaricalarins A–E (1–5), and two known analogues (6 and 7) were isolated from the roots and rhizomes of Ligularia songarica. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for in vitro cytotoxic activity against cultured A-549, MCF-7, KB, and KBVIN cells, and 4 exhibited cytotoxicity with EC50 values of 4.9, 0.8, 3.4, and 3.2 µg/mL, respectively

Acetophenone Monomers from Acronychia trifoliolata

Seven new [acronyculatins I-O (1-7)] and four known acetophenone monomers were isolated from a CH 3 OH/CH 2 Cl 2 (1:1) extract (N089419) of Acronychia trifoliolata provided by the U.S. National Cancer Institute (NCI, Frederick, MD, USA). Their structures were characterized by using various NMR and HRMS techniques. Among the known compounds, the structure of acronyculatin B (8) was revised. Some of the isolated compounds were evaluated for antiproliferative activity against human cancer cell lines. While most of the tested compounds were not cytotoxic, acronyculatins I (1) and J (2) showed moderate antiproliferative activity

Anti-AIDS Agents 81. Design, Synthesis, and Structure−Activity Relationship Study of Betulinic Acid and Moronic Acid Derivatives as Potent HIV Maturation Inhibitors †

In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl- betulinic acid (MSB) analogs were also designed to better understand the contribution of the C-3′ dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3) was also employed to study the influence of the backbone and the C-3 modification towards the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents, and led to the design and synthesis of compound 12 (EC50: 0.0006 μM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor