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• Nine different oleanane-type glycosides were isolated. • Their structures were elucidated by extensive spectroscopic analyses. • The chemotaxonomy of the Weigela genus was discussed, based on the structure of the isolated glycosides. • The cytotoxicity of some isolated compounds was evaluated on three cancer cell lines. • The monodesmosidic oleanolic acid derivatives displayed a good cytotoxicity with IC 50 ranging from 2.19 to 2.83 μM. Nine different oleanane-type glycosides were extracted and isolated by various chromatographic methods from two Weigela florida cultivars, "Pink Poppet" and "Jean's Gold". From the roots of W. florida "Pink Poppet", three monodesmosidic oleanolic acid saponins 1 , 4 , 5 were obtained, together with one hederagenin ester 6 from the leaves, and six bidesmosidic saponins 2, 3, 6-9 were isolated from the leaves of W. florida "Jean's Gold". Among compounds 1 - 9 , three were previously undescribed (1 - 3) and six (4 - 9) were already published in the literature. Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESI-MS). The cytotoxicity of the isolated compounds 1, 3, 4, 6, 7, 9 , against mouse colon carcinoma (CT26), mouse melanoma (B16) and human liver cancer (HepG2) cell lines, was evaluated by MTS assay. The ester group at C-28 and/or the primary alcohol function at C-23 led to a negative effect, whereas monodesmosidic oleanolic acid glycosides displayed a good cytotoxicity with IC 50 ranging from 2.19 to 2.83 μM. A key sequence in the structure of the molecules was proposed for the cytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP inhibitors that have been shown to be efficacious against certain types of cancers has given rise to a new field of research that investigates the activity of these compounds in other incurable human diseases such as fibrotic disorders. The aim of this review is to discuss new findings regarding the involvement of HSPs in the pathogenesis of organ fibrosis and to note recent discoveries that indicate that HSPs could be important therapeutic targets to improve the current dismal outcome of fibrotic diseases. [Copyright &y& Elsevier]

Steroidal glycosides are known to possess a wide range of biological activities such as cytotoxicity and antimicrobial effects. To isolate more of these glycosides to get a better understanding at their structure/activity relationship, and to complete chemotaxonomic information, a cultivated Yucca rostrata was studied, along with a wild and a cultivated Dracaena braunii. Thirteen spiro- and furostan glycosides were isolated from those plants and their structure were elucidated using 1D and 2D NMR. Since they were already reported from other plant species, it allowed us to get an idea on which type of structure might be specific to which taxon. The compounds from D. braunii were tested for their antimicrobial activity against Candida albicans, C. glabrata and Staphylococcus aureus. Only compound 12 (CAS 39491-39-9) showed a weak activity on S. aureus with a MIC of 50 μg/mL. The compounds from Y. rostrata were tested for their cytotoxicity against a CT26 (murine colorectal carcinoma) cell line. The spirostan glycosides 4 (CAS 119459-80-2) and 5 (CAS 164592-97-6) showed an interesting activity with an IC 50 of 2.38 μM and 2.26 μM, respectively. Comparing the structures of the active versus the inactive ones, we were able to formulate some hypotheses regarding the structure/activity relationships, in accordance with the current literature. • Yucca rostrata and Dracaena braunii as source of steroidal saponins. • Isolation of thirteen known steroidal glycosides brings new chemotaxonomic data. • Evaluation of weak antimicrobial activity against Staphylococcus aureus. • Description of a strong cytotoxic effect against CT26 cells. [ABSTRACT FROM AUTHOR]

Seven previously undescribed oleanane-type glycosides were isolated from the trunk barks of a Central African tree named Millettia laurentii De Wild (Fabaceae). After the extraction from the barks, the isolation and purification of these compounds were achieved using various solid/liquid chromatographic methods. Their structures were established mainly by 1D and 2D NMR (COSY, TOCSY, ROESY, HSQC, HMBC) and mass spectrometry (ESI-MS), as 3- O -β-D-glucuronopyranosyl-(1 → 2)-β-D-glucuronopyranosylechinocystic acid, 3- O -β-D-apiofuranosyl-(1 → 3)-β-D-glucuronopyranosyl-(1 → 2)-β-D-glucuronopyranosylechinocystic acid, 3- O -β-D-apiofuranosyl-(1 → 3)-β-D-galactopyranosyl-(1 → 2)-β-D-glucuronopyranosylechinocystic acid, 3- O -β-D-apiofuranosyl-(1 → 3)-[β- d -xylopyranosyl-(1 → 2)]-β-D-galactopyranosyl-(1 → 2)-β-D-glucuronopyranosylechinocystic acid, 3- O -β-D-apiofuranosyl-(1 → 3)-[α-L-arabinofuranosyl-(1 → 2)]-β-D-galactopyranosyl-(1 → 2)-β-D-glucuronopyranosylechinocystic acid, 3- O -α-L-arabinofuranosyl-(1 → 2)-β-D-galactopyranosyl-(1 → 2)-β-D-glucuronopyranosyloleanolic acid, 3- O -β-D-apiofuranosyl-(1 → 3)-[α-L-arabinofuranosyl-(1 → 2)]-β-D-galactopyranosyl-(1 → 2)-β-D-glucuronopyranosyloleanolic acid. In addition, the cytotoxicity of six glycosides among the isolated ones, was evaluated against 4 T1 cell line from a mouse mammary gland tissue, using MTS method. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemotherapy with anti PD-1/PD-L1 antibodies has become the standard of care for patients with metastatic non-small cell lung cancer (mNSCLC). Using lung tumor models, where pemetrexed and cisplatin (PEM/CDDP) chemotherapy remains unable to synergize with immune checkpoint inhibitors (ICIs), we linked the failure of this treatment with its inability to induce CXCL10 expression and CD8+ T cell recruitment. Using drug screening, we showed that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion by cancer cells and CD8+ T cell recruitment, sensitizing it to ICIs. PEM/CDDP plus a MEKi promotes optineurin (OPTN)-dependent mitophagy, resulting in CXCL10 production in a mitochondrial DNA- and TLR9-dependent manner. TLR9 or autophagy/mitophagy inhibition abolishes the anti-tumor efficacy of PEM/CDDP plus MEKi/anti-PD-L1 therapy. In human NSCLCs, high OPTN , TLR9 , and CXCL10 expression is associated with a better response to ICIs. Our results underline the role of TLR9- and OPTN-dependent mitophagy in enhancing chemoimmunotherapy efficacy. [Display omitted] • MEK inhibition synergizes with chemotherapy to induce CD8+ T cell recruitment in TME • Active KRAS-MEK pathway negatively regulates optineurin-dependent mitophagy • TLR9-dependent mitochondrial DNA sensing during mitophagy induces CXCL10 expression • MEK inhibitor and chemotherapy combination synergizes with PD-L1 blockade Limagne et al. show that simultaneous treatment by chemotherapy and MEK inhibitors promotes mitophagy and mitochondrial DNA recognition by TLR9. TLR9 signaling leads to CXCL10 expression in cancer cells and CD8+ T cell recruitment to tumors and improves efficacy of PD-L1 blockade. [ABSTRACT FROM AUTHOR]

A phytochemical study of Cordyline fruticosa "Fairchild red" (Asparagaceae) from Vietnam, led to the isolation of fourteen steroidal glycosides, including twelve previously undescribed along with two known ones. Ten compounds were obtained by successive solid/liquid chromatographic methods from an aqueous-ethanolic extract of the roots, and four from the aerial parts. Their structures were elucidated mainly by spectroscopic analysis 2D NMR and mass spectroscopy (ESI-MS), as spirostanol glycosides, 5α-spirost-25(27)-ene-1β,3β,4α-triol 1- O -β-D-fucopyranoside, 5α-spirost-(25)27-ene-1β,3β,4α-triol 1- O -β-D-xylopyranoside, 5α-spirost-(25)27-ene-1β,3β,4α-triol 1- O -α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranoside, 5α-spirost-(25)27-ene-1β,3β,4α-triol 1- O -α-L-rhamnopyranosyl-(1 → 2)-(4- O -sulfo)-β-D-fucopyranoside, 5α-spirost-25(27)-ene-1β,3β-diol 1- O -α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranoside, and 5α-spirost-25(27)-ene-1β,3β-diol 1- O -α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranoside. Furostanol glycosides were also isolated as 26- O- β-D-glucopyranosyl-5α-furost-(25)27-ene-1β,3β,4α,22α,26-pentol 1- O- β-D-fucopyranoside, 26- O -β-D-glucopyranosyl-22α-methoxy-5α-furost-(25)27-ene-1β,3β,4α,26-tetrol 1- O -β-D-fucopyranoside, 26- O- β-D-glucopyranosyl-5α-furost-(25)27-ene-1β,3β,22α,26-tetrol 1- O- β-D-glucopyranoside, 26- O- β-D-glucopyranosyl-5α-furost-(25)27-ene-1β,3β,22α,26-tetrol 1- O- α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside, 26- O -β-D-glucopyranosyl-5α-furost-(25)27-ene-1β,3β,22α,26-tetrol 1- O -α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranoside, and 26- O -β-D-glucopyranosyl-22α-methoxy-5α-furost-(25)27-ene-1β,3β,26-triol 1- O -α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranoside. All the isolated compounds were further evaluated for their cytotoxicity against 4T1 cell line, from a mouse mammary gland tissue, using MTS method. Fourteen steroidal glycosides, twelve undescribed, were isolated from Cordyline fruticosa (L.) A.Chev. , cultivar "Fairchild red" (Asparagaceae). Their cytotoxicity was evaluated using MTS method. [Display omitted] • A phytochemical study of Cordyline fruticosa "Fairchild red" (Asparagaceae) from Vietnam was achieved. • Fourteen steroidal glycosides were isolated, twelve previously undescribed and two known ones. • Their structures were elucidated mainly by 2D NMR and mass spectrometry (ESI-MS). • Six of them were spirostane-type glycosides and six of the furostane-type. • Their cytotoxicity against a 4T1 cell line was evaluated. [ABSTRACT FROM AUTHOR]

Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity. [Display omitted] • Design of efficient aza-BODIPY-based homo-bimetallic gold(I) theranostics. • High in vitro anti-proliferative properties (4 < IC 50 < 10 μM on 4 cancer cell lines). • Significant anti-cancer effect of aza-BODI-Au-1 in tumor-bearing BALB/c mice. • The compounds can be tracked in vitro and in vivo by NIR-optical imaging. [ABSTRACT FROM AUTHOR]

Seven oleanane-type glycosides were extracted and isolated by various chromatographic methods from the roots of Weigela x "Bristol Ruby" (1 – 7), six previously undescribed (1 – 6) and a known one (7). Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESIMS). Selected triterpenoid glycosides (1 – 3 , 6 , 7) displayed a good cytotoxic activity against a mouse colon cancer cell line CT26. Unlabelled Image [ABSTRACT FROM AUTHOR]