Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

Antiproliferative and apoptosis-inducing potential of 3β-hydroxy-△5-steroidal congeners purified from the soft coral Dendronephthya putteri

The exploration and identification of antiproliferative phytochemicals have received increased attention in medicinal chemistry. In particular, research focused on the toxicology of marine natural products has increased in recent years. Terpenoids, among many secondary metabolites, have been demonstrated to act as effective anticancer agents. Soft corals, a group of marine invertebrates, produce a variety of terpenoids with biofunctional properties. The current study presents the extraction, purification, and identification of sterol congeners from the soft coral Dendronephthya putteri. The method involves 50% chloroform-methanol extraction, polar column fractionation, and analysis through GC-MSn. Dose-dependent antiproliferative activity was observed within the sterol-rich fraction (DPCMH 2-4), which consisted of 3β-hydroxy-Δ5-steroidal congeners. This fraction inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 25.27±1.43 and 22.81±0.15 μg/mL, respectively. Apoptotic body formation, DNA damage, cell cycle arrest, and apoptotic cell signaling pathway activation were also observed, reinforcing the dose-dependent antiproliferative and apoptosis-inducing activity of 3β-hydroxy-Δ5-steroidal congeners. To our knowledge, this is the first report of anticancer agent identification from the soft coral D. putteri. Based on the observations, these steroidal congeners are promising candidates for the development of anticancer drugs.

Synthesis,Crystal Structure and Antiproliferative Activity of Ethyl 1-(Phenylcarbamoyl)-2-3,4,5-trimethoxyphenyl)cyclopropanecarboxylae

Many small-molecule compounds have been evaluated with potential antiproliferative activities. Ethyl 1-（phenylcarbamoyl）-2-（3,4,5-trimethoxyphenyl）cyclopropanecarboxylate, one novel cyclopropylamide analogue of combretastatin-A4（CA-4）, has been synthesized and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n, with a = 15.0263（3）, b = 7.6574（2）, c = 19.4117（4）, β = 111.9010（10）o, V = 2072.36（8）3, Z = 4, C22H24NO6, Mr = 398.42, Dc = 1.277 Mg/cm3, F（000） = 844, λ（MoKα） = 1.54178 , μ = 0.770 mm–1, R = 0.0546 and wR = 0.1889 for 3319 observed reflections（I 〉 2σ（I））. Meanwhile, the compound revealed potential antiproliferative activities in several cancer cells in vitro.

Antiproliferative Properties of Vinyl Dipeptides: Synthesis and MCF-7 Cell Line Testing

Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.

Crystal Structure and Antiproliferative Activity of Ethyl 3,9-Dihydroxy-9-methyl-7-phenyl-7,8,10-trihydro-6Hdibenzo[b,d]pyran-6-one-8-carboxylate

Ethyl 3,9-dihydroxy-9-methyl-7-phenyl-7,8,10-trihydro-6H-dibenzo[b,d]pyran-6-one-8-carboxylate（C（23）H（22）O6,Mr = 394.42） has been synthesized and its structure was determined by ~1H and ^（13）C NMR,ESI-MS,elemental analysis,and X-ray single-crystal diffraction.The crystal belongs to the triclinic system,space group P1,with a = 8.8220（17）,b = 9.881（2）,c = 12.157（2） A,α= 90.488（3）,β= 102.664（4）,γ= 98.799（3）°,V= 1020.8（3） A^3,Z= 2,Dc = 1.342 g/cm^3,μ= 0.099mm^（-1）,F（000） = 436,R = 0.0615 and wR = 0.2501 for 2592 observed reflections with（I2σ（I））.In the crystal structure,the coumarin ring system is planar and the 3：4 fused cyclohexane ring adopts distorted half-chair conformation.Rich hydrogen bonding interactions are formed between compound 2 and lattice water molecules.These interactions assemble molecules of 2 into 2D layered networks in an AB stacking sequence.Its in vitro antiproliferative activities against three human cancer cell lines were evaluated by MTT assay.

Design,synthesis and antiproliferative activities of novel 5H-pyridazino[4,5-b]indoles

A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds. The structures were confirmed by ^1H NMR and MS. Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro. Three of compounds （1e, 1g, and 1h） exhibited potent antiproliferative activities, especially compound lh （with IC50 values of 5.2 μmol/L and 1.9 μmol/L against Bel-7402 and HT-1080, respectively）. The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.

Synthesis, Crystal Structure and Antiproliferative Activity of 2-(((5-(((5,7-Dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidin-2-yl)thio)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)-4Hchromen-4-one Methanol Solvate

The novel crystal of the title compound 2-（（（5-（（（5,7-dimethyl-[1,2,4]triazolo-[1, 5-a]-pyrimidin-2-yl）thio）methyl）-4-phenyl-4H-1,2,4-triazol-3-yl）thio）methyl）-4H-chromen-4-one methanol solvate（C27H25N7O3S2, Mr = 559.66） has been prepared and its structure was determined by single-crystal X-ray diffraction. The crystal belongs to the monocline system, space group P21/c with a = 11.9879（9）, b = 14.0743（10）, c = 15.9706（11）A, β = 98.509（2）°, V = 2664.9（3）A3, Z = 4, Dc = 1.395 g/cm^3, F（000） = 1168, μ = 0.116 mm-1, MoKa radiation（λ = 0.71073）, R = 0.0652, and wR = 0.1425 for 5220 observed reflections with I 〉 2σ（I）. X-ray diffraction analyses reveal that the molecule adopts a C-shape. The planes of the benzopyrone and triazolopyrimidine were nearly parallel to each other, with a dihedral angle of 1.21（3）°. Intramolecular and intermolecular hydrogen bonds together with π-π interations are found to exist in the structure. The results of MTT assay indicate that the title compound displays excellent antiproliferative activity against two human cancer cell lines.

Gap junctions enhance the antiproliferative effect by transfer of microRNAs in glioma cells

OBJECTIVE To investigate the permeability of gap junction composed of connexin 43(Cx43)for micro RNAs(mi RNAs)and the impact of gap junction-mediated transfer of mi RNAs in glioma U87 cells.METHODS Co-culture assay demonstrated the transmission of miR NAs through gap junction channel into adjacent cells.U87 cells were labeled with green fluorescein protein(GFP)as receivers and cells were transfected mi RNAs as donors.Receiver cells and donor cells were mixed together in a ratio of 1∶1.After 12 h co-culture,cells were separated using a BD influx flow cytometer based on the GFP labeled.Quantitative real-time polymerase chain reaction(q RT-PCR)was applied detect to the expressions of miR NAs and Cx43 mR NA.Western blotting was performed to detect the protein expressions of Cx43 and GFP in U87 cells.CCK-8 assay is used to detect cell growth.RESULTS Co-culture assays demonstrated mi R-34a could transfer between U87 cells.The role of the contact independent could also transfer of miR-34a.Gap junctions inhibitor(CBX and 18-α-GA)showed lower miR-34a expression than co-culture group,whereas gap junctions enhancer(RA and Galanglin)enhanced miR-34a expression.Knockdown of Cx43 could significantly decrease the transferring of miR-34a between U87 cells.Different length of miR NAs(miR-1827,miR-144,miR-203a and miR-1183)were similar to the expression of miR-34a between U87 cells.Additionally,we demonstrated that gap junctions mediate the effect of antiproliferation mediated by mi R-34a in U87 cells.The functional inhibition of gap junctions using either si RNA or inhibition eliminated the miR-34a mediated antiproliferation,whereas the enhancement of gap junctions treatment augmented this mi R34a-mediated antiproliferation.CONCLUSION Our study demonstrates that gap junction composed of Cx43-mediated transfer mi RNAs in different length of nucleotides and gap junction-mediated transfer of mi R-34a enhance the antiproliferative effect in glioma U87 cells.

Synthesis, Crystal Structure and Antiproliferative Activity of 2,2-Dimethyl-4-oxochroman-3-ylmorpholine-4-carbodithioate

The crystal structure of the new title compound 2,2-dimethyl-4-oxochroman-3-ylmorpholine-4-carbodithioate（C16H19NO3S2,Mr = 337.44） has been prepared and determined by single-crystal X-ray diffraction.The crystal is of triclinic,space group P1 with a = 9.5518（7）,b = 9.7172（7）,c = 11.0220（8）,α = 67.08（1）,β = 74.66（1）,= 61.31（1）°,V = 822.72（10）3,Z = 2,Dc = 1.362 g/cm3,F（000） = 356,μ = 0.092 mm-1,MoKa radiation（λ = 0.71073）,R = 0.0515 and wR = 0.1389 for 2623 observed reflections with I 2（I）.X-ray diffraction analysis reveals that the chroman ring adopts a half-chair conformation while the morpholine ring shows a chair conformation.Intramolecular and intermolecular C–H···S and C–H···O hydrogen bonds together with π-π interations are found in the structure.The result of MTT assay shows the title compound displays good antiproliferative activity against two human cancer cell lines.

Antiproliferative effect of extracts of Sida rhombifolia L.(Malvaceae)on the Allium cepa cell cycle

Field collected roots of four populations of Sida rhombifolia were used for preparing aqueous de-coctions at two concentrations:4g/L;and 16g/L.Afterwards,we used three groups of six onion(Allium cepa)bulbs for testing each population.Slides were made with all bulbs through the smashing technique.Cells in all phases of the cell cycle of A.cepa were analyzed.The mitotic index(%of cells in mitosis)was calculated,and the statistical analysis through theχ2 test was carried out at 5%probability.The results showed that the aqueous extracts of S.rhombifolia have antiproliferative activity at high concentrations.Practically no chromosomal ab-errations were induced by treatments.

Design,synthesis and antiproliferative activity of novel 2,7-disubstituted triazolo[1,5-a]pyrimidines

In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines （6-16）. Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds （9-11 and 16） displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.

Synthesis and Antiproliferative Activity of Novel [1,2,4]Triazolo[1,5-a]pyrimidine-7-amine Derivatives

A series of novel N-anilino-2-substituted-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-amine derivatives was prepared and evaluated for their in vitro antiproliferative activity against two cancer cell lines,Bel-7402 and HT-1080.Most of the compounds inhibited the cell proliferation at a low concentration.Seven compounds,VI5,VI7,VI10,and VI12―VI15,possessed marked antiproliferative activity superior to that of cisplatin.Of these seven initial hits,compound VI10 was the most active.

Antiproliferative Triterpenoid Saponins from Leptaulus citroides Baill. from the Madagascar Rain Forest

Bioassay-guided fractionation of EtOH extracts obtained from the roots and wood of the Madagascan plant Leptaulus citroides Baill.(Cardiopteridaceae)led to the isolation of ethyl esters of three new triterpenoid saponins(1–3)and the known sesquiterpenoid cinnamosmolide(4).The structures of 1–3 were elucidated by extensive 1D and 2D NMR experiments and mass spectrometry.Compounds 1,2,and 4 showed moderate cytotoxicity against the A2780 human ovarian cancer cell line with IC50 values of 2.8,10.2 and 2.0 lM,respectively.

Antiproliferative Activity of “<i>Lycopersicon esculentum</i>” Leaves (Var. Paul Robenson): Preliminary Study

Among plants, the Lycopersicon esculentum (Solanaceae) is the most important for its beneficial effects on health. Several epidemiological studies have shown the benefits of tomato consumption in the cancer and cardiovascular disease prevention. Tomato products constitute the major source of lycopene, the most potent antioxidant among carotenoids in vitro. In tomatoes leaves are also present many secondary metabolites including phenolic compounds, phytoalexins, protease inhibitors and glycoalkaloids who protect against adverse effects of hosts including fungi, bacteria, viruses, and insects and are involved in host-plant resistance. In this work we evaluated the antiproliferative activity of tomato leaves extract (var. Paul Robenson) in vitro.

Comparative Antiproliferative Action of Two Extracts from <i>Tilia x viridis</i>on Normal and Tumoral Lymphocytes: Rela-tionship with Antioxidant Activity

Tilia species have been used in Asia, Europe and in America to treat anxiety and also for the treatment of colds and inflammation. The oxygen reactive species (ROS) (hydrogen peroxide (H2O2) and the superoxide anion (O2) are involve in the balance cell proliferation/death in lymphocytes. It was reported the presence of flavonoids in Tilia species which possess antioxidant properties. The aim of this study was to determine comparatively the effect of an aqueous (AE) and ethanol (E) extract from Tilia x viridis, on the proliferation of tumoral and normal concanavalin A stimulated murine lymphocytes in relation to antioxidant activities such as peroxidase (Px), catalase (CAT) and superoxide dismutase (SOD) activities involves in H2O2 modulation. Also a phytochemical pattern of the two extracts in relation to flavonoids content was determined. Both extracts presented antiproliferative action on both type of lymphocytes but E was more selective on the tumoral lymphocytes inhibition (EC50 (μg/ml, Mean ±SEM) (tumoral): 50 ± 4;EC50;(normal lymphocytes): 323 ± 20);this action was related to a high polyphenols content (150 ± 10 mg/g extract) and high “per se” SOD and low Px activities. In conclusion, the extracts could be a source of antioxidant compounds which contribute to a selective antiproliferative action on tumoral cells, acting through the modulation of H2O2 levels.

Broad-Spectrum Antiproliferative Activity of Diarylureas and Diarylamides Possessing Pyrrolo[3,2-c]Pyridine Scaffold

A series of diarylureas and diarylamides possessing pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 49 cell lines of eight different cancer types at the NCI and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities with superior potencies to Sorafenib. Compounds 8a, 9d and 9f showed lethal effect with mean %inhibition more than 100% over the 49 tested cell lines. In addition, the mean %inhibition results of compounds 8d, 8e, 9e, 9g and 9h were more than 80%. And most of the IC50 values of the target compounds were in submicromolar scale. Compounds 8a, 9b and 9e demonstrated high selectivity towards cancer cell lines compared with NIH3T3 fibroblasts.

The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Total synthesis of cajanine and its antiproliferative activity against human hepatoma cells

Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.

Design,synthesis and antiproliferative activities of diaryl urea derivatives bearing N-acylhydrazone moiety

A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line （HL-60）, human lung adenocarcinoma epithelial cell line （A549） and human breast cancer cell line （MDA-MB-231） in vitro by standard MTT assay. The pharmacological results indicated that some compounds exhibited promising antitumor activities. Compound 1j showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L, 0.7 μmol/L and 0.5μmol/L, respectively.

Simultaneous Screening and Analysis of Anti-inflammatory and Antiproliferative Compounds from Euphorbia maculata Combining Bio-affinity Ultrafiltration with Multiple Drug Targets

Euphorbia maculata has long been used for managing different impairments in Asian countries.However,its antioxidant,anti-inflammatory and antiproliferative potentialities,along with its potential bioactive compounds remain unexplored.In this context,a bio-a ffinity ultrafiltration strategy was developed to fish out ligand candidates against Cycloxygenase-2(COX-2),Topoisomerase I(Topo I),and TopoisomeraseⅡ(TopoⅡ).Thereafter,lead compounds activities were assessed in silico and in vitro for ascertaining the screening results and forecasting its corresponding activities.As a result,the E.maculata ethyl acetate(EMEA)fraction showed interesting COX-2 inhibition activity with an IC 50 value of 0.67±0.09μg/mL,as well as good growth inhibitions for three malignant cell lines.EMEA chemical fingerprinting was also conducted to enable a tentative identification of 17 compounds,among which,11 were assessed as ligand candidates to COX-2,8 compounds to Topo I,and 10 compounds to TopoⅡ.Dihydromyricetin and quercetin-3-O-arabinoside were revealed to be multipotent compounds which exerted good a ffinity to the three targeted enzymes,and also supported with their molecular docking simulations and in vitro assay validations.The interrelationship between E.maculata’s associated activities(antioxidant,anti-inflammatory and antiproliferative)was revealed with the corresponding multipotent phytochemical active components from this work.It also provided a useful direction for its empirical traditional use and further explorations in the near future.