Chemical constituents from the seeds of Cullen corylifolium and their inhibitory activity on diacylglycerol acyltransferase.

A large number of extracts of medicinal plants or natural products shows beneficial to combat obesity. In the present work, a new flavonoid named (2S,1″R,2″R)-4'-hydroxy-7-methoxy-6-(1,2,3-trihydroxy-3-methyl-butyl)-flavanone (1), along with seven known compounds (2-8) were isolated from the seeds of Cullen corylifolium. Their structures, including the absolute configurations, were determined by the analysis of comprehensive spectroscopic data and computational calculation methods. All isolates were evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity. Compounds 1-4 exhibited different level of DGAT1 inhibitory activity with IC50 values ranging from 28.2 ± 1.1 to 127.3 ± 1.9 µM. In addition, 45 flavonoids which be evaluated for DGAT inhibitory activity were summarised and potential structure-activity relationships were discussed.

Aaptamine derivatives with CDK2 inhibitory activities from the South China Sea sponge Aaptos suberitoides.

Three new aaptamines (1-3) together with two known derivatives (4-5) were isolated from the South China Sea sponge Aaptos suberitoides. The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds 3-5 showed moderate cytotoxicities against H1299 and H520 cells with IC50 values ranging from 12.9 to 20.6 µg/mL. Besides, compounds 3-5 also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC50 values of 14.3, 3.0 and 6.0 µg/mL, respectively. In addition, compounds 3-5 significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound 3 could effectively bind with CDK2 protein and protect it from the degradation by pronase.

Scutellariabarbata D. Don extraction selectively targets stemness-prone NSCLC cells by attenuating SOX2/SMO/GLI1 network loop.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellariabarbata D. Don extraction (SBE), a traditional Chinese medicine, has been proved effective against various malignant disorders in clinics with tolerable side-effects when administered alone or in combination with conventional chemotherapeutic regimens. AIM OF THIS STUDY: Multi-drug resistance of cancer is attributed to existence of cancer stemness-prone cells that harbor aberrantly high activation of Sonic Hedgehog (SHH) cascade. Our previous study has demonstrated that SBE sensitized non-small cell lung cancer (NSCLC) cells to Cisplatin (DDP) treatment by downregulating SHH pathway. Yet, whether SBE could prohibit proliferation of cancer stemness-prone cells and its underlying molecular mechanisms remain to be investigated. In this article, we further investigated intervention of SBE on NSCLC cell stemness-associated phenotypes and its potential mode of action. MATERIALS AND METHODS: CCK-8 and clonal formation detection were used to measure the anti-proliferative potency of SBE against NSCLC and normal epithelial cells. Sphere formation assay and RQ-PCR were used to detect proliferation of cancer stemness cells and associated marker expression upon SBE incubation. Mechanistically, DARTS-WB and SPR were used to unveil binding target of SBE. Immunodeficient mice were implanted with patient derived tumor bulk for in vivo validation of anti-cancer effect of SBE. RESULTS: SBE selectively attenuated proliferation and stemness-like phenotypes of NSCLC cells rather than bronchial normal epithelial cells. Drug-protein interaction analysis revealed that SBE could directly bind with stem cell-specific transcription factor sex determining region Y-box 2 (SOX2) and interfere with the SOX2/SMO/GLI1 positive loop. In vivo assay using patient-derived xenografts (PDXs) model further proved that SBE diminished tumor growth and SOX2 expression in vivo. CONCLUSION: Our data indicate that SBE represses stemness-related features of NSCLC cells via targeting SOX2 and may serve as an alternative therapeutic option for clinic treatment.

Triazole derivatives and their antiplasmodial and antimalarial activities.

Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates.

Quinoline and quinolone dimers and their biological activities: An overview.

Quinoline and quinolone motifs which act as structural subunits of more complex natural products are ubiquitous in nature, and they are useful pharmacophores which play a pivotal role in drug development. Compared with the corresponding monomeric compounds, the dimers usually exhibited some unique properties, so dimers have caused great interests in recent years. Quinline and quinolone dimers possess various biological properties such as antibacterial, anticancer, antimalarial and antitubercular activities, and some of them which are exemplified by piperaquine have already used in clinical practice. Numerous quinline and quinolone dimers have been synthesized and screened for their in vitro and in vivo biological activities, and some of them exhibited promising potency. Therefore, quinline and quinolone dimers have the potential for clinical deployment in the control and eradication of various diseases. This review covers the recent advances of quinline and quinolone dimers as bioactive substances. The structure-activity relationship was also discussed to provide an insight for rational designs of more active quinline and quinolone dimers.

Cytotoxic and Antiviral Triterpenoids from the Mangrove Plant Sonneratia paracaseolaris.

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A-E (1-4, and 11) together with twelve known analogues (5-10, 12-17). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC50 value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC50 value of 28.4 µg/mL. A preliminary structure activity relationship was discussed.

Imidazole Alkaloids from the South China Sea Sponge Pericharax heteroraphis and Their Cytotoxic and Antiviral Activities.

Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole alkaloid named naamidine J (1) along with four known ones (2-5). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed a central 2-aminoimidazole ring, substituted by one or two functionalized benzyl groups in some combination of the C4 and C5 positions. The cytotoxicities against selected HL-60, HeLa, A549 and K562 tumor cell lines and anti-H1N1 (Influenza a virus (IAV)) activity for the isolates were evaluated. Compounds 1 and 2 exhibited cytotoxicities against the K562 cell line with IC50 values of 11.3 and 9.4 µM, respectively. Compound 5 exhibited weak anti-H1N1 (influenza a virus, IAV) activity with an inhibition ratio of 33%.

Polyhydroxylated steroids from the South China Sea soft coral Sarcophyton sp. and their cytotoxic and antiviral activities.

Chemical investigation on the soft coral Sarcophyton sp. collected from the South China Sea yielded three new polyhydroxylated steroids, compounds (1-3), together with seven known ones (4-10). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed the 3ß,5α,6ß-trihydroxylated steroidal nucleus. The cytotoxicities against selected HL-60, HeLa and K562 tumor cell lines and anti-H1N1 (Influenza A virus (IAV)) activities for the isolates were evaluated. Compounds 2, 3 and 5-8 exhibited potent activities against K562 cell lines with IC50 values ranging from 6.4 to 10.3 µM. Compounds 1, 6-8 potently inhibited the growth of HL-60 tumor cell lines, and 6 also showed cytotoxicity towards HeLa cell lines. In addition, preliminary structure-activity relationships for the isolates are discussed. The OAc group at C-11 is proposed to be an important pharmacophore for their cytotoxicities in the 3ß,5α,6ß-triol steroids. Compounds 4 and 9 exhibited significant anti-H1N1 IAV activity with IC50 values of 19.6 and 36.7 µg/mL, respectively.