Novel halogenated arylvinyl-1,2,4 trioxanes as potent antiplasmodial as well as anticancer agents: Synthesis, bioevaluation, structure-activity relationship and in-silico studies.

Cancer remains the leading cause of death worldwide, with breast cancer being the most prevalent disease diagnosed globally. Liver cancer is the fourth most common cause of death globally, while prostate cancer accounts for the second most frequent malignancy among males worldwide. The main treatment options for cancer include surgery, radiation therapy, and chemotherapy. The stem bark of Tieghemella heckelii has been exploited for its medicinal properties. On a broader scale, research on the anticancer properties of T. heckelii has not been explored. It is therefore important to investigate the anticancer potential of the leaves of T. heckelii. The goal of the study was to evaluate the in vitro anticancer activities of the leaves of T. heckelii on breast, prostate, and liver cancer cell lines. The leaves of T. heckelii were collected from Asantemanso, Akim Oda, in the eastern region of Ghana. Authenticity of the leaves was performed at the Department of Plant and Environmental Biology, University of Ghana. Aqueous and ethanol extraction were performed on the leaves of T. heckelii after grinding into fine particles, followed by low-temperature drying. Breast cancer (MDA-MB-468), liver cancer (HepG2), and normal kidney (Vero E6) cell lines were cultured in DMEM media, while prostate cancer (PC3) cell lines were cultured in RPMI medium. Anticancer activity of the leaves of T. heckelii was conducted on breast (MDA-MB-468), liver (HepG2), and prostate (PC3) cancer cell lines. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Both ethanolic and aqueous extracts demonstrated similar cytotoxicity for the HepG2 cell line, with IC50 values of about 200 μg/mL. selectivity index of > 2 was recorded by all cell lines. When compared to other cell lines, the aqueous extract for prostate cancer showed the lowest IC50 value with a selectivity of 8. In addition, the extracts showed less cytotoxic activity against the normal (Vero) cell line. Leaves of T. heckelii possess cytotoxic properties with notable selectivity against prostate (PC3) and liver (HepG2) cancer cell lines. However, findings should be evaluated in in vivo studies because biological processes can be more complex in living organisms. Further investigation should be conducted to ascertain the bioactive compounds responsible for the anticancer activity.

A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins 1a-b, a number of α-amino acids 2a-e and (E)-2-aryl-1-nitroethenes 3a-e in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using 1H and 13C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound 4l was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3'-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3'-oxindoles] analogs 4a-w against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3'-oxindoles], while five compounds (4c, 4f, 4m, 4q, 4t) (IC50 = 34.99-47.92 µM; SI = 0.96-2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (4c, 4f, 4k, 4m, 4q, 4t) (IC50 = 41.56-86.53 µM; SI = 0.49-0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC50 = 100 µM) and chloroquine (IC50 = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC50 = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC50 = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].

Cancer is among the top global public health burdens leading to millions of deaths each year. The study aims to investigate the antiproliferative effect of Spartium junceum L. flowers on different cancer cell lines. The ethanolic extract of the flowers was prepared in the present study. Phytochemical analysis of the plant extract revealed the presence of several phenolic compounds such as cinnamic acid and its derivatives (chlorogenic, p-coumaric, ferulic acids), protocatechuic acid, epicatechin and luteolin. This extract was tested against human breast (MDA-MB-231) and liver (HepG2) cancer cell lines to find out its antiproliferative activity. It was determined that the extract was effective against both cell lines with IC50 values of 2.37 ± 0.47 and 0.98 ± 0.01 µL/mL for MDA-MB-231 and HepG2, respectively. Particularly, the extract was found to be more effective in the liver cancer cell line than the breast cancer cell line. All these obtained findings led us to believe that this medicinal plant could be a promising antiproliferative agent candidate for the treatment of human liver and breast cancers.

Artemisinin-inspired novel functionalized aryloxy-arylvinyl-1,2,4-trioxanes as potent anticancer agents: Design, synthesis, bioevaluation, SAR and in silico studies

Several chromene derivatives have a wide variety of biological and pharmacological activity. They had anticancer activity, antimicrobial activity, antituberculosis activity, anticonvulsant activity, antidiabetic activity, antichlolinesterase activity, and inhibitor of monoamine oxidase activity. The above-mentioned activities directed us to synthesize novel chromene derivatives, chromeno[2,3-d][1,3]oxazines, and chromeno[2,3-d]pyrimidines. The starting material was 2- amino-8-(2-chlorobenzylidene)-4-(2-chlorophenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. Several novel chromene derivatives had been synthesized. Compound 1 reacted with carbon disulfide, and ethyl chloroformate to afford chromene derivatives 2, 3. Chromene derivative 3 reacted with hydrazine dydrate to give compound 4. Chromene derivative 1 reacted with acetic acid and sulphuric acid to produce compounds 5, and 6. Amino derivative 5 reacted with chloroacyl derivative to afford compounds 7a-c which cycalized in dry xylene to afford compounds 8a-c. Chromene derivative 8a reacted with hydroxyl amine to afford compound 9. The structures of novel synthesized chromene derivatives had been confirmed using mass spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Most of the prepared compounds were screened against liver cancer cell lines (HepG-2), human colon cancer cell lines (HT-29), and breast adenocarcinoma cell lines (MCF-7). Chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. The rest of the tested compounds had anticancer activity against human colon cancer cell lines (HT-29) lower than that of the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Several chromene derivatives had been synthesized and their structures had been confirmed using different spectroscopic techniques. Some of the chromene derivatives that were screened against different cancer cell lines showed promising anticancer activity higher than the reference standard drug. For example, chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Chromene derivative 6 had anticancer activity against breast adenocarcinoma cell lines (MCF-7) higher than the standard drug.

The aim of the present study was to explore the role of miR‑493-5p in liver cancer tissues and cell lines, and its effect on cell behavioral characteristics. The expression of miR-493-5p was detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR) in liver cancer tissues and cell lines (hepatic cell line HL-7702 and the liver cancer cell lines HCCC-9810, HuH-7 and HepG2). In addition, the mechanism by which miR-493-5p mediates its effects was analyzed via the transfection of miR-493-5p mimic and negative control miRNA into HepG2cells. The viability, proliferation, apoptosis and invasion of the cells were analyzed using MTT assay, flow cytometry and Transwell chamber experiments. Furthermore, the effect of miR-493-5p on the expression of vesicle associated membrane protein2(VAMP2) was assayed using a dual-luciferase reporter system, and VAMP2 protein levels were determined by western blot analysis. In addition, following the cotransfection of HepG2 cells with pcDNA3.1‑VAMP2 plasmid and miR‑493-5p mimic, the role of miR-493-5p as a regulator of VAMP2 was evaluated using MTT assay, flow cytometry and Transwell chamber experiments. RT-qPCR analysis indicated that the expression of miR-493-5p in liver cancer tissues and cell lines was decreased significantly compared with that in adjacent normal liver tissues and normal liver cell lines, respectively. Compared with the control group, the cells transfected with miR-493-5p mimic (the miR-493-5p overexpression group) exhibited reduced cell viability, a reduced percentage of cells in the Sphase and an increased percentage of apoptotic cells. In addition, fewer cells passed through the Transwell membrane in the miR-493-5p overexpression group compared with the control group. In the dual-luciferase reporter assay, luciferase activity in the miR‑493-5p overexpression group was attenuated compared with that in the control group. Inaddition, western blot analysis indicated that the VAMP2 protein levels in the miR‑493-5p overexpression group were lower than those in the control group. Furthermore, in cells overexpressing miR-493-5p and VAMP2 simultaneously, the biological behavior of the cells, including cell viability, cell cycle and cell invasiveness, was significantly rescued compared with that of the control group transfected with miR‑493-5p alone. In conclusion, miR-493-5p is indicated to be a tumor suppressor gene, and is downregulated in human liver cancer. miR-493-5p overexpression promotes cell apoptosis and inhibits the proliferation and migration of liver cancer cells by negatively regulating the expression of VAMP. These observations suggest the potential of treating liver cancer by the overexpression of microRNA-493-5p.

Design, Synthesis, Structure‐Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl‐1,2,4‐Trioxanes as Potent Antiplasmodial as well as Anticancer Agents

α-Mangostin-rich extract (AME) shows promise as a functional ingredient for cancer chemotherapy. Here, we encapsulated AME in our originally designed antioxidant nanoparticles (NanoAOX) to increase its solubility and prevent oxidative degradation (AME@NanoAOX). In this study, two types of self-assembled polymers containing nitroxide radicals were engineered. These polymers were self-assembled into nanoscale particles in aqueous media, entrapping AME (abbreviated as AME@NanoAOX(B) and AME@NanoAOX(G)). These formulations considerably improved the stability of AME against oxidative degradation and exhibited different release profiles of α-mangostin under different pH conditions. Furthermore, AME-encapsulated nanoparticles exhibited potent cytotoxicity against various cancer cell lines, including human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Caco-2), human cervical cancer (HeLa), and human liver cancer (HepG2) cell lines, with minimal cytotoxicity in normal human mammary epithelial cells (hTERT-HME1), thus providing a high selectivity index (SI). These results indicated the promising feature of AME-encapsulated antioxidant nanoparticles (AME@NanoAOX) for cancer chemotherapy.

Five compounds including quercetin (AC01), asparagine (AC02), sucrose (AC03), β-sitosterol-3-O-β-D-glucopyranoside (AC04) and β-sitosterol (AC05) were isolated from the methanol extract of Asparagus cochinchinensis (Lour.) Merr. tuber collected in Ba Ria–Vung Tau Province of Vietnam. Their structures were elucidated by NMR (1D and 2D-NMR). Quercetin (AC01) was subjected to the assay for antioxidant and anticancer activities. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay was employed for determining the antioxidant activity, while sulforhodamine B (SRB) method was applied for evaluating the anticancer activity against four selected human cancer cell lines. Quercetin had strong antioxidant activity with IC50 = 14.52 ± 2.12 µg/ml (as compared to standard vitamin C with IC50 = 10.49 ± 2.00 µg/ml). Meanwhile, quercetin (AC01) exhibited strong cytotoxicity against the HeLa, human cervical cancer cell line with IC50 = 5.78 ± 0.36 µg/ml, followed by lung cancer cell line (NCI–H460), lung cancer cell line with IC50 = 12.57 ± 1.19 µg/ml and liver cancer cell line (Hep-G2) liver cancer cell line with IC50 = 20.58 ± 0.85 µg/ml. The anticancer activity of quercetin against breast cancer cell line (MCF-7), breast cancer cell line was recorded with IC50 = 31.04 ± 3.14 µg/ml. Key words: Asparagus cochinchinensis, 1,1-diphenyl-2-picrylhydrazyl (DPPH), sulforhodamine B (SRB), human cervical cancer cell line (HeLa), lung cancer cell line (NCI-H460), breast cancer cell line (MCF-7), liver cancer cell line (Hep-G2).

Advances in chalcone derivatives: Unravelling their anticancer potential through structure-activity studies

A synthesis of bis- and poly(imidazoles) by one-pot three-component reaction of 1,2-diketone with aldehydes and ammonium acetate in the presence of catalytic amount of ZnO nanocatalyst is reported. The reactions were performed under conventional heating as well as under microwave irradiation. The anticancer activities of the synthesized compounds were evaluated against human breast adenocarcinoma cell line (MCF-7), liver cancer cell line (HepG-2), and epithelial colorectal adenocarcinoma cells (CaCO-2). The results of the cytotoxic activity revealed that compound 16 b with bis(imidazole) analog that incorporated a 4,5-difuran rings was potent against HepG-2 cancer cells (IC50 = 8.14 µM) with high selectivity index (SI = 27.47). Compound 25 incorporating four imidazole units was active against MCF-7 cell line (IC50 = 12.62 µM) and showed a significant selectivity index (SI = 7.71). Moreover, compound 27 containing six imidazole units exhibited the highest activity against the CaCO-2 cell line (IC50 = 32.51 μM) with SI = 4.09.

Anticancer, antibacterial and pollutant degradation potential of silver nanoparticles from Hyphaene thebaica

Phenolic profiling of edible parts Hyphaene thebaica ( Doum palm) are identified using LC-ESI-MS, the Overall polyphenolic constituents demonstrated by means of LC-ESI-Mass profiling . Twenty three isolated compounds were identified as ; caffeic acid, protocatechuic acid, rhamnetin, catechin, quercitrin, vanillic acid , kaempferol 3-O-acetyleglucoside , cinnamic acid, apigenin-7-O-glucose , intricatin 3-O-htyrosol, luteolin, quercetin ,naringenin , kaempferol ,vanillic acid 4-β-D-glycoside coumaric acid, ferulic acid, luteolin-6-arbinose-8-glucose, p-coumaroyl malic acid eriocitrin, apigenin and hesperetin Iron nanoparticles (FeNps ) of H. thebaica fruit EtOAc extract was freshly prepared and characterized with Dynamic Light Scattering (DLS) with particles size 150.7 nm. The anti-proliferation activity of the crude extract of EtOAc and the synthesized Fe Nps was evaluated using MTT assay on human colon (Caco-2) and liver (HepG2) cancer cell lines. The results declared that half maximal inhibitory concentration (IC50) of EtOAc extract on colon (IC50 35.4 µg/ml) and on liver cancer cell lines (IC50 72.02 µg/ml) while nanoparticles portion of EtOAc was found more pronounced on colon cancer cell lines (IC50 19.44 µg/ml) and on liver (IC50 15.5 µg/ml). So, the Fe Nps of EtOAc of H.thebaica fruit extract with particles size 150.7 nm is more effective as antitumor than the crude EtOAc extract.

Antiproliferative and antioxidant properties of nematocysts crude venom from jellyfish Acromitus flagellatus against human cancer cell lines

Green coating of metal and metal oxide nanomaterials is currently recognized as an eco-friendly route to magnify their biological efficacy and reduce risks due to low biocompatibility. In this study, bio-fabricated metallic silver nanoparticles (AgNPs) were synthesized using three medicinal plant extracts, i.e. Eclipta prostrata, Moringa oleifera and Thespesia populnea and then tested for their cytotoxic activity against human prostate (PC3) and liver (HepG2) cancer cell lines. The green fabricated AgNPs were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential analysis, dynamic light scattering, scanning electron microscopy and energy dispersive X-ray spectroscopy. Biofabricated AgNPs exhibited dose-dependent increase in cell toxicity on human prostate cancer, liver cancer and African monkey kidney cell lines. IC50 values of PC3, HepG2 and Vero cells varied depending upon the source used for nanoparticle synthesis. DNA fragmentation, Hoechst, rhodamine and AO/EtBr staining assays confirmed nano-triggered apoptosis of treated cells. The main achievement of this study is that nanofabrication routes relying to E. prostrata, M. oleifera and T. populnea medicinal plant extracts to fabricate Ag nanocomplex within 2 h duration can represent a novel cancer nanodrug and effective way to boost their anticancer efficacy.