Exploring the Anticancer Potential of Premna resinosa (Hochst.) Leaf Surface Extract: Discovering New Diterpenes as Heat Shock Protein 70 (Hsp70) Binding Agents.

Premna, a genus consisting of approximately 200 species, predominantly thrives in tropical and subtropical areas. Many of these species have been utilized in ethnopharmacology for diverse medicinal applications. In Saudi Arabia, Premna resinosa (Hochst.) Schauer (Lamiaceae) grows wildly, and its slightly viscid leaves are attributed to the production of leaf accession. In this study, we aimed to extract the surface accession from fresh leaves using dichloromethane to evaluate the anticancer potential. The plant exudate yielded two previously unknown labdane diterpenes, Premnaresone A and B, in addition to three already described congeners and four known flavonoids. The isolation process was accomplished using a combination of silica gel column chromatography and semi-preparative HPLC, the structures of which were identified by NMR and HRESIMS analyses and a comparison with the literature data of associated compounds. Furthermore, we employed a density functional theory (DFT)/NMR approach to suggest the relative configuration of different compounds. Consequently, we investigated the possibility of developing new chaperone inhibitors by subjecting diterpenes 1-5 to a Surface Plasmon Resonance-screening, based on the knowledge that oridonin, a diterpene, interacts with Heat Shock Protein 70 (Hsp70) 1A in cancer cells. Additionally, we studied the anti-proliferative activity of compounds 1-5 on human Jurkat (human T-cell lymphoma) and HeLa (epithelial carcinoma) cell lines, where diterpene 3 exhibited activity in Jurkat cell lines after 48 h, with an IC50 of 15.21 ± 1.0 µM. Molecular docking and dynamic simulations revealed a robust interaction between compound 3 and Hsp70 key residues.

Rhanteriol, a New Rhanterium suaveolens Desf. Lignan with Pharmacological Potential as an Inhibitor of Enzymes Involved in Neurodegeneration and Type 2 Diabetes.

Several specialized plant metabolites are reported to be enzyme inhibitors. In this investigation, the phytochemical composition and the biological activity of Rhanterium suaveolens Desf. were studied. One new lignan (rhanteriol 1) and seven known secondary metabolites were isolated from the aerial parts of R. suaveolens by using different chromatographic procedures. The biological properties of the R. suaveolens extracts and the new compound were evaluated by measuring their ability to inhibit the cholinesterase and carbohydrate-hydrolyzing enzymes, using cell-free in vitro methods. The new lignan, rhanteriol, was shown to inhibit α-amylase and α-glucosidase (IC50 = 46.42 ± 3.25 µM and 26.76 ± 3.29 µM, respectively), as well as butyrylcholinesterase (IC50 = 10.41 ± 0.03 µM), with an effect comparable to that of the respective standards, acarbose and galantamine. Furthermore, docking studies were performed suggesting the interaction mode of rhanteriol with the active sites of the investigated enzymes. The obtained data demonstrated that the aerial part of R. suaveolens could represent a source of active molecules, such as rhanteriol, usable in the development of treatments for preventing or treating type 2 diabetes mellitus and neurodegeneration.

LC-ESI/MS-Phytochemical Profiling with Antioxidant, Antibacterial, Antifungal, Antiviral and In Silico Pharmacological Properties of Algerian Asphodelus tenuifolius (Cav.) Organic Extracts.

Asphodelus tenuifolius Cav. (A. tenuifolius) is a medicinal plant with a long history of traditional use to treat ailments. In this study, total phenolic and flavonoid content evaluation using LC-ESI/MS analysis and various biological activities (antioxidant, antibacterial, antifungal, antiviral and cytotoxicity) of organic extracts from the aerial parts of A. tenuifolius were analyzed. ADME tools were used to predict the potential of the identified compounds from the most potent extract as specific drugs. As shown, LC-ESI/MS results of chloroformic extract allowed the tentative identification of 12 compounds. Chloroformic extract was rich in polyphenols and flavonoids and exhibited the highest antioxidant activity given by DPPH (IC50 = 25 µg/mL) as compared to the BHT standard (11.5 µg/mL) and ß-carotene bleaching assays (IC50 = 95.692 µg/mL). Antibacterial activity results showed that chloroformic extract has a highest activity against Gram-positive and -negative bacteria, especially against Salmonella Typhimurium DT104 (IZ = 19.3 mm, MIC = 18.75 mg/mL, MBC = 37.5 mg/mL). The MBC/MIC ratio was evaluated to interpret the activity that was bacteriostatic rather than bactericidal. Conversely, weaker antifungal activity was registered, and no antiviral activity was observed for all extracts against Herpes Simplex Virus type 2 and Coxsakievirus B-3 viruses. Cytotoxic activity on VERO cell line results revealed that butanol extract was not toxic, with CC50 value of 1430 µg/mL, while chloroformic extract showed moderate cytotoxicity. Additionally, in silico studies performed proved promising pharmacokinetic and drug-likeness properties of the main compounds from the chloroformic extract. Taken together, this work highlights the potent bioactivity and acceptable drug-likeness of this plant, which supports its further preclinical development.

Glucopyranosylbianthrones from the Algerian Asphodelus tenuifolius: Structural Insights and Biological Evaluation on Melanoma Cancer Cells.

Two new glucopyranosylbianthrones (1 and 2) were isolated from the aerial part of the plant Asphodelus tenuifolius, collected in Southwest Algeria. The 2D structures of 1 and 2 were defined by NMR analysis, HRESIMS data, and comparison with literature data. The comparison of experimental and calculated electronic circular dichroism and NMR data led to characterization of the ( M) and ( P) atropisomeric forms of the glucopyranosylbianthrones, asphodelins (1) and (2), respectively. The in vitro activities of these two metabolites were evaluated in human melanoma A375 cells, and both the compounds inhibited cell proliferation in a concentration-dependent manner, with IC50 values of 20.6 ± 0.8 and 23.2 ± 1.1 µM, respectively. Considering their biological profile, an inverse virtual screening approach was employed to identify and suggest putative anticancer interacting targets.

A new glucosidic iridoid from Isodon rubescens

ABSTRACT One new glucosidic iridoid, 6-O-veratroylbarlerin, was isolated from the chloroform/methanol extract of Isodon rubescens (Hemsl.) H.Hara, Lamiaceae aerial parts, along with the known compounds apigenin and caffeic acid. The structure of the new compound was elucidated on the basis of 1D and 2D NMR experiments and ESI-MS technique.