Isolation and characterisation of pharmaceutically versatile molecules from Rumex dentatus and evaluation of their cytotoxic activity against human cancer cell lines.

The disclosed study reveals isolation, characterization and anticancer evaluation of Rumex dentatus. The extracts and isolated compounds were used for cytotoxic activity against (lung (A549), pancreatic (MIAPaCa), colon (HCT-116), breast (MDA-MB-231) and breast (MDA-MB-468) cell lines. The extracts were screened for cytotoxicity using MTT colorimetric assay. Out of all extracts, methanolic (30) %: chloroform fraction (TAW6) with 75.01% inhibition at a concentration 100 µg/mL was observed. The selected extracts were further processed for column chromatography and led to isolation of seven compounds (A to G). The structural determination of isolated compounds was carried out using 1HNMR, 13CNMR, IR and HRMS. All the isolates were tested for cytotoxic activity and compound B was found most active with IC50 values 11.29 µg against HCT-116 (Colon). The compound B was then used for detailed study via transwell invasion assay and wound healing assay. Thus the significant anticancer activity particularly against colon cancerous cell lines recommends that the (Rumex dentatus) could act as a potential drug candidate for cancer, more particularly for colon cancer.

An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells.

Withania somnifera exhibits different pharmacological activities which mainly stem from its broad range of bioactive molecules. Majority of these bioactive molecules, fall into the groupings of alkaloids, steroidal lactones, phenolic compounds and glycoproteins. In this study, we evaluated a novel protein fraction, named here as WSPF, isolated from Withania somnifera roots for its cytotoxic properties against various human cancer cell lines. WSPF exhibited apoptotic activity for each cancer cell line tested, demonstrating significant activity against MDA-MB-231 human breast cancer cells with an IC50 value of 92 µg/mL. WSPF induced mitochondrial-mediated apoptosis of MDA-MB-231 cells via extensive reactive oxygen species generation, dysregulation of Bax/Bcl-2, loss of mitochondrial membrane potential and caspase-3 activation. Additionally, we observed G2/M-phase cell cycle arrest, cleavage of nuclear lamin A/C proteins, and nuclear morphological changes. The present results highlight the anti-cancer properties of WSPF, indicating that the proteins in this fraction can be potential therapeutic agents for triple negative breast cancer treatment.

Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model.

In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of ∼33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.