Synthesis and anticancer activity of novel halolactones with β-aryl substituents from simple aromatic aldehydes

A series of 20 novel racemic iodo-, bromo- and chlorolactones, possessing β-phenyl-γ-lactone or β-phenyl-δ-lactone framework, were synthesized from commercially available aromatic aldehydes in convenient five-step syntheses. Some of them showed noticeable cytotoxic effect against two cancer lines, Jurkat (human leukaemia) and D17 (canine osteosarcoma). The highest activity, comparable with carboplatin, was observed for cis-5-(1-iodoethyl)-4-(4′-isopropylphenyl)dihydrofuran-2-one against Jurkat cell line.     

4‐Chlorothiazole‐5‐carbaldehydes as Potent Precursors for Synthesis of Some New Pendant N‐heterocyces Endowed with Anti‐Tumor Activity

In our approach to synthesize bioactive molecules, a series of novel N‐heterocycles were synthesized and evaluated for their in vitro antitumor activity against a panel of three human cancer cell lines, namely, human breast cancer cell line (MCF‐7), human cervical cancer cell line (HeLa), and human prostate cancer PC‐3. The majority of the tested compounds exhibited significant cytotoxic activity toward the tested tumor cell lines. Analogues 33 , 34 , 31 , 38 , 21 , 23 , 22 , and 20 exhibited considerable cytotoxic activities comparable with standard drug 5‐fuorouracil. Compound 33 displayed superior cytotoxicity with IC₅₀ value of 4.12 ± 1.21 μg/mL against HeLa tumor cell line.     

Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy

Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of Garcinia nujiangensis, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G_0/1 arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs.     

Naringenin Induces ROS-Mediated ER Stress,Autophagy, and Apoptosis in Human Osteosarcoma Cell Lines

Osteosarcoma, a primary bone tumor, responds poorly to chemotherapy and radiation therapy in children and young adults; hence, as the basis for an alternative treatment, this study investigated the cytotoxic and antiproliferative effects of naringenin on osteosarcoma cell lines, HOS and U2OS, by using cell counting kit-8 and colony formation assays. DNA fragmentation and the increase in the G2/M phase in HOS and U2OS cells upon treatment with various naringenin concentrations were determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Annexin V/propidium iodide double staining, respectively. Flow cytometry was performed, and 2′,7′-dichlorodihydrofluorescein diacetate, JC-1, and Fluo-4 AM ester probes were examined for reactive oxygen species (ROS) generation, mitochondrial membrane potential, and intracellular calcium levels, respectively. Caspase activation, cell cycle, cytosolic and mitochondrial, and autophagy-related proteins were determined using western blotting. The results indicated that naringenin significantly inhibited viability and proliferation of osteosarcoma cells in a dose-dependent manner. In addition, naringenin induced cell cycle arrest in osteosarcoma cells by inhibiting cyclin B1 and cyclin-dependent kinase 1 expression and upregulating p21 expression. Furthermore, naringenin significantly inhibited the growth of osteosarcoma cells by increasing the intracellular ROS level. Naringenin induced endoplasmic reticulum (ER) stress-mediated apoptosis through the upregulation of ER stress markers, GRP78 and GRP94. Naringenin caused acidic vesicular organelle formation and increased autophagolysosomes, microtubule-associated protein-light chain 3-II protein levels, and autophagy. The findings suggest that the induction of cell apoptosis, cell cycle arrest, and autophagy by naringenin through mitochondrial dysfunction, ROS production, and ER stress signaling pathways contribute to the antiproliferative effect of naringenin on osteosarcoma cells.     

Pllans–II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress

Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans–II, a phospholipase A₂ type–Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line—Ca Ski—related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub–expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes′ sub–expression at the protein level. In addition, Pllans–II presented a dose–dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans–II inhibited cancer cells′ adhesion and migration capacity, induced cell cycle arrest in the G2/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans–II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.     

Determination of Cytotoxic Activity of Selected Isoquinoline Alkaloids and Plant Extracts Obtained from Various Parts of Mahonia aquifolium Collected in Various Vegetation Seasons

Melanoma is a serious form of skin cancer that begins in cells known as melanocytes. While it is less common than the other forms of skin cancer, melanoma is more dangerous because of its ability to spread to other organs more rapidly if it is not treated at an early stage. The number of people diagnosed with melanoma has increased over the last few decades. The most widely used treatments include surgery, chemotherapy, and radiation therapy. The search for new drugs to treat various cancers is one of the most important challenges of modern scientific research. Some isoquinoline alkaloids found in different plant species have strong cytotoxic effects on various cancer cells. We tested the effect of isoquinoline alkaloids and extracts obtained from various parts of Mahonia aquifolium collected in various vegetation seasons on human melanoma cancer cells and our data indicated that investigated extract induced significant reduction in cell viability of Human malignant melanoma cells (A375), human Caucasian malignant melanoma cell line (G361), and human malignant melanoma cell line (SKMEL3 cancer cell lines in a dose- and time-dependent manner. Differences in cytotoxic activity were observed for extracts obtained from various parts of Mahonia aquifolium. Significant differences were also obtained in the alkaloids content and cytotoxic activity of the extracts depending on the season of collection of plant material. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments in order to confirm the possibility of their use in the treatment of human melanomas.     

In Vitro Phytochemical Screening,Cytotoxicity Studies of Curcuma longa Extracts with Isolation and Characterisation of Their Isolated Compounds

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (¹H Proton and ¹³C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC₅₀value of 11.27 μg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC₅₀ value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC₅₀ value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.     

Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line

Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.     

A Bioactive Compound from Sanguisorba officinalis L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells

Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, Sanguisorba officinalis L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic.     

Ionic liquid mediated synthesis and in vitro mechanistic exploration of polycyclic cage-like heterocyclic hybrid

A three-component, [3 + 2]-cycloaddition/annulation domino protocol is described for the synthesis in excellent yield of a polycyclic cage-like heterocyclic hybrid (PCHH) that comprises various advantaged structural units viz., α,β-unsaturated ketone moiety, 4-pyridinone and pyrroloisoquinoline in a cage-like framework. The antitumor activity of PCHH on human breast (MCF7), colon (HCT116), cervical (JURKAT) and lung (NCI-H460) malignant cell lines inhibited the propagation of all cell lines. This hybrid molecule displayed increased broad-spectrum anticancer activity with higher doses of PCHH. Furthermore, the compound induced 45.21% of early apoptosis and 46.32% of late apoptosis in the Jurkat cancer cell line. Cell cycle analysis showed that this cage-like compound caused cell cycle arrest of Jurkat cells at the S phase and sub G0/G1 phase. Additionally, it led to increased DNA fragmentation and mitochondrial membrane permeabilization through activation of caspase-3 enzyme. Present investigation demonstrates the specific cytotoxic activity of the cage-like compound and the induction of apoptosis through the intrinsic pathway of Jurkat cells.     

Photochemical and phototoxic properties of ethyl 1,4-dihydro-8-nitro-4-oxoquinoline-3-carboxylate, a new quinoline derivative

The present study demonstrates photoinduced generation of superoxide radical anion and singlet oxygen upon UVA irradiation of ethyl 1,4-dihydro-8-nitro-4-oxoquinoline-3-carboxylate (DNQC), and its cytotoxic/phototoxic effects on murine leukemia L1210 cells. The formation of reactive oxygen species (ROS) was investigated by EPR spectroscopy using in situ spin trapping technique and 4-hydroxy-2,2,6,6-piperidine (TMP) for singlet oxygen ((1)O(2)) detection. The EPR spectra monitored upon photoexcitation of aerated solutions of DNQC in dimethylsulfoxide evidenced the efficient activation of molecular oxygen via Types I and II mechanisms. The cytotoxic/phototoxic effects of DNQC, analysis of cell cycle, induction of apoptosis/necrosis, DNA damage and molecular mechanism of apoptotic death of L1210 cells in dark and in the presence of UVA irradiation were compared. DNQC induced a different cytotoxic/phototoxic effect, which was concentration- and time-dependent. The four highest tested concentrations of non-photoactivated and photoactivated DNQC induced immediate cytotoxic/phototoxic effect after 24h cultivation of L1210 cells. This effect decreased with the time of treatment. The irradiation increased the sensitivity of leukemia cell line on DNQC, but the cell sensitivity decreased with time of processing. Quinolone derivative DNQC significantly induced direct DNA strand breaks in L1210 cells, which were increased with the irradiation of cells. The DNA damage generated by DNQC alone/with combination of UVA irradiation induced cell arrest in G(0)/G(1) and G(2)/M phases, decrease in the number of L1210 cells in Sphase and apoptotic cell death of certain part of cell population after 24 h of influence. DNQC alone/with combination of UVA irradiation induced apoptosis in L1210 cells through ROS-dependent mitochondrial pathway.     

Enhanced Cytotoxic Effect of Doxorubicin Conjugated to Glutathione-Stabilized Gold Nanoparticles in Canine Osteosarcoma—In Vitro Studies

Osteosarcoma (OSA) is the most common malignant bone neoplasia in humans and dogs. In dogs, treatment consists of surgery in combination with chemotherapy (mostly carboplatin and/or doxorubicin (Dox)). Chemotherapy is often rendered ineffective by multidrug resistance. Previous studies have revealed that Dox conjugated with 4 nm glutathione-stabilized gold nanoparticles (Au-GSH-Dox) enhanced the anti-tumor activity and cytotoxicity of Dox in Dox-resistant feline fibrosarcoma cell lines exhibiting high P-glycoprotein (P-gp) activity. The present study investigated the influence of Au-GSH-Dox on the canine OSA cell line D17 and its relationship with P-gp activity. A human Dox-sensitive OSA cell line, U2OS, served as the negative control. Au-GSH-Dox, compared to free Dox, presented a greater cytotoxic effect on D17 (IC₅₀ values for Au-GSH-Dox and Dox were 7.9 μg/mL and 15.2 μg/mL, respectively) but not on the U2OS cell line. All concentrations of Au-GSH (ranging from 10 to 1000 μg/mL) were non-toxic in both cell lines. Inhibition of the D17 cell line with 100 μM verapamil resulted in an increase in free Dox but not in intracellular Au-GSH-Dox. The results indicate that Au-GSH-Dox may act as an effective drug in canine OSA by bypassing P-gp.     

Design,Synthesis and Molecular Modeling of Nonsteroidal Anti‐inflammatory Drugs Tagged Substituted 1,2,3‐Triazole Derivatives and Evaluation of Their Biological Activities

A novel series of 1,4‐disubstituted‐1,2,3‐triazole derivatives 3a – l and 5a – i were one‐pot synthesized via CuAAC‐alkyne click chemistry and evaluated for their antibacterial activity against four organisms and screened for their anticancer activity against human colon cancer cell line HT‐29 and human lung cancer cell line HTB‐29. These hybrid molecules structure elucidation has been performed by IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral analysis. Synthesized nonsteroidal anti‐inflammatory drugs‐triazoles evaluated for their antibacterial activities against bacterial microorganisms Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumonia. Final compounds 3i , 3c , and 5b showed magnificent broad spectrum activity against P. aeruginosa, K. pneumonia, E. coli, and S. aureus with zone of inhibition values of 20, 15, 17, and 16 mm, respectively. Among the series of compound, 3j showed the best antibacterial activity against all the strains. Further, the compounds 3i and 5a were more cytotoxic than cisplatin against all tested two human cancer cell lines, with 50.8%, and 52.3% and 73.4% and 75.3% of growth, respectively. The synthesized compounds were tested for kinase inhibitory activity against glycogen synthase kinase‐3 protein kinases, in addition, for cytotoxic activity against two different human cancer cell lines.     

Arenicolsterol A，来自海洋环节动物海蚯蚓中的一种新的细胞毒性烯醇式磺化甾醇

Marine organisms are the important source of the bioactive metabolites. A novel enolic sulfated sterol, arenicolsterol A, has been isolated from a marine annelid Arenicola cristata collected in the coast of Mainland of China.The structure was elucidated using all sorts of spectroscopic data including ESIMS, 1D and 2D NMR etc. The cytotoxic bioactivity of this sterol was evaluated by MTT assay. It could inhibit the growth of human cervix cancer cell line (Hela) and human non-small cell lung cancer cell line (NCI-h6) with IC50 of (3.1 0.6)μg/mL and (7.6 0.8)μg/mL.     

Retracted: Synthesis,Molecular Properties,and Biological Evaluation of Hybrid 1,2,3‐Triazolylpolyaza Heterocyclic Compounds

In this research article, a highly efficient, cost‐effective synthesis of various hybrid molecules possessing 1,2,3‐triazolyltetrazoles and evaluation of their biological activity have been addressed. The structure elucidation of these new library hybrid molecules has been carried out by IR, ¹H NMR, ¹³C NMR, and mass spectral analysis. The compounds have been screened for their anticancer activity against human colon cancer cell line Colo‐205 and human lung cancer cell line HOP‐205, and the results attest that most of the compounds have shown very good therapeutic nature. In particular, compounds 3d , 3j , 6a , and 6e were more cytotoxic than Adriamycin against all tested human cancer cell lines with 68%, 101.8%, 94%, and 104.5% growth, respectively. In the present investigation, a series of 3a – j and 6a – h were subjected to molecular properties prediction, drug likeness by Molinspiration, and toxicity risks by Molsoft software programs. All the 18 analogues were chosen on the basis of Lipinski “Rule of five” for the synthesis, screening their antibacterial and anticancer as oral bioavailable drugs/leads.     

An In Vitro Anticancer,Antioxidant, and Phytochemical Study on Water Extract of Kalanchoe daigremontiana Raym.-Hamet and H. Perrier

Kalanchoe species are succulents with anti-inflammatory, antioxidant, and analgesic properties, as well as cytotoxic activity. One of the most popular species cultivated in Europe is Kalanchoe daigremontiana Raym.-Hamet and H. Perrier. In our study, we analyzed the phytochemical composition of K. daigremontiana water extract using UHPLC-QTOF-MS and estimated the cytotoxic activity of the extract on human ovarian cancer SKOV-3 cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, luminometric, and fluorescent microscopy techniques. The expression levels of 92 genes associated with cell death were estimated via real-time PCR. The antioxidant activity was assessed via flow cytometry on human keratinocyte HaCaT cell line. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical and FRAP (ferric-reducing antioxidant power) assays were also applied. We identified twenty bufadienolide compounds in the water extract and quantified eleven. Bersaldegenin-1,3,5-orthoacetate and bryophyllin A were present in the highest amounts (757.4 ± 18.7 and 573.5 ± 27.2 ng/mg dry weight, respectively). The extract showed significant antiproliferative and cytotoxic activity, induced depolarization of the mitochondrial membrane, and significantly arrested cell cycle in the S and G2/M phases of SKOV-3 cells. Caspases-3, 7, 8, and 9 were not activated during the treatment, which indicated non-apoptotic cell death triggered by the extract. Additionally, the extract increased the level of oxidative stress in the cancer cell line. In keratinocytes treated with menadione, the extract moderately reduced the level of oxidative stress. This antioxidant activity was confirmed by the DPPH and FRAP assays, where the obtained IC₅₀ values were 1750 ± 140 and 1271.82 ± 53.25 μg/mL, respectively. The real-time PCR analysis revealed that the extract may induce cell death via TNF receptor (tumor necrosis factor receptor) superfamily members 6 and 10.     

New synthetic quinaldine conjugates: Assessment of their anti-cholinesterase,anti-tyrosinase and cytotoxic activities,and molecular docking analysis

Despite all the progress made to enrich the existing bank of drugs used to treat and cure Alzheimer and cancer patients, there is still a need to research and develop new bioactive candidates with superior efficacy but minimal side effects. In this context, a new series of anti-butyrylcholinesterase (anti-BChE), anti-tyrosinase and cytotoxic succinimide linked quinaldine conjugates 3a-i was designed and synthesized starting from 8-hydroxyquinaldine. The condensation of quinoleine-hydrazide 2 with electrophilic species such as aromatic and nonaromatic anhydrides provided the new compounds 3a-i. These synthesized heterocycles were characterized by spectroscopic means (¹H NMR, ¹³C NMR and ESI-HRMS). Their anti-butyrylcholinesterase, anti-tyrosinase and cytotoxic (cervical cancer cell (HeLa) and lung cancer cell (A549)) activities have been evaluated in vitro. Compounds 3e and 3 g were found to be more anti-BChE than Galanthamine. Compounds 3d, 3e and 3 g exerted better anti-tyrosinase activity than kojic acid. Also, 3a, 3f and 3 g showed interesting cytotoxic potential towards HeLa cell lines. These results were supported by the molecular docking analysis (structure–activity relationship (SAR)) to estimate and discuss possible interactions between these derivatives and active sites of proteins butyrylcholinesterase (PDB: 4B0P), tyrosinase (PDB: 2Y9X) and cytotoxic (topoisomerase IIα enzyme (PDB: 5GWK)).     

New cytotoxic cardenolide glycoside from the seeds of Cerbera manghas

A new cytotoxic cardenolide glycoside, 3beta-O-(2'-O-acetyl-alpha-L-thevetosyl)-14beta-hydroxy-7-en-5beta-card-20(22)-enolide, (7,8-dehydrocerberin), together with five known cardenolides, 17beta-neriifolin, deacetyltanghinin, tanghinin, cerberin and 2'-O-acetyl-cerleaside A were isolated from the seeds of Cerbera manghas L. Their structures were elucidated by 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. 7,8-Dehydrocerberin, deacetyltanghinin and tanghinin exhibited cytotoxic activities against oral human epidermoid carcinoma (KB), human breast cancer cell (BC) and human small cells lung cancer (NCI-H187).     

Study on the structure-activity relationships of phoxalone and induction of apoptosis in H446 tumor cells

A novel macrolide with dioxa and double ring pentadecanone, named as phoxalone, isolated from the culture broth of a myxobacterium Sorangium cellulosum WXNXJ-C, was well investigated. The chemical structure of Phoxalone was elucidated by spectroscopic analysis including UV, IR, (1)H NMR, MALDI-TOF-MS, and LC/MS spectra. The results of cytotoxic bioactivities on human non-small lung cancer H446, in vitro, showed that not only did phoxalone express higher antitumor bioactivity than many antitumor drugs, but it also displayed less cytotoxicity to normal human liver L02 cell lines (IC(50), 286 microg mL(-1)). Further cytotoxic bioactivity study indicated that phoxalone could induce H446 cell line apoptosis in vitro. More investigation results of flow-cytometric analysis suggested that phoxalone arrested the mitosis of H446 cell line at G2/M phase. Hence, phoxalone and its derivatives or analogs would reveal huge research value and fascinating foreground.     

Synthesis,cytotoxicity and apoptosis-inducing activity of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid

With the expectation of finding new and effective antitumor drugs, a series of novel N-(1H-benzo[d]imidazole-2-yl)-benzamide/benzenesulfonamide derivatives of dehydroabietic acid were synthesized and evaluated for cytotoxic activity against three human cancer cell lines (MCF-7, HeLa, and HepG2 cells) and one human normal hepatocyte cell line (LO2). As a result, a number of derivatives showed moderate to good antitumor activities. Among them, compound 8h exhibited the most potent activities against three cancer cell lines with IC₅₀ values of 0.87 ± 0.18, 9.39 ± 0.72, and 8.31 ± 0.64 μM, respectively, and was less active to normal hepatocyte LO2 cells. Further mechanism studies revealed that compound 8h could arrest the cell cycle of MCF-7 cells at S phase and induce the apoptosis of MCF-7 cells in ROS-mediated mitochondrial pathway.