Echinophora tenuifolia L. branches phytochemical profile and antiproliferative activity on human cancer cell lines

Abstract

The methanolic extract of Echinophora tenuifolia L. branches and its fractions were evaluated for their in vitro cell growth inhibitory activity on different human cancer cell lines (C32, LoVo and SKBr3) and the normal BJ fibroblasts. All tested samples were effective against the melanoma cell line C32, with IC₅₀ values ranging from 22.8?±?0.8 to 78.7?±?1.2?μg/mL, the antiproliferative activity of the dichloromethane fraction being significantly higher. This fraction was also effective against the LoVo adenocarcinoma cell line, with an IC₅₀ value of 53.0?±?2.1?μg/mL. The ethyl acetate and dichloromethane fractions showed the highest lipid peroxidation inhibitory activity, verified by means of the β-carotene bleaching test. The phytochemical profiles of E. tenuifolia branches extract were established by means of GC-MS and HPTLC. Overall, branches of E. tenuifolia L. could represent a rich source of bioactive compounds, potentially useful in the pharmaceutical field.     

Study on the Synthesis and Bioactivity of Novel Mahkoside A Derivatives

Abstract

A series of novel Mahkoside A derivatives was synthesized, and their in vitro cytotoxic activities were evaluated against the human cancer cell line Ec‐9706. A Preliminary structure–activity relationship study showed compounds 7 and 8 have obvious cytotoxic activities (IC₅₀: 30.0 and 12.5 µg · mL^?1, respectively).     

Synthesis of novel heptaplatin derivatives and evaluation of their ability to inhibit proliferation of cancer cell lines

A series of novel heptaplatin derivatives were synthesized and evaluated for their ability to inhibit growth of two cancer cell lines: human colon carcinoma cell line HCT-8 and human hepatocarcinoma cell line Bel-7402. Majority of the synthesized compounds demonstrated superior activity against cancer cell lines compared to heptaplatin. Specifically, compounds 5a and 5b (5 µg/mL) had more pronounced efficacy against the HCT-8 cell line while 6b and 6c (0.5 µg/mL) had higher efficacy against Bel-7402 cell line.     

Iodine-catalyzed three-component one-pot synthesis of novel 1,8-dioxo-decahydroacridines derivatives bearing benzene sulfonamide moiety

An efficient synthetic method for 1,8-dioxo-decahydroacridines derivatives bearing the biologically active sulfonamide moiety is described. Aromatic aldehyde reacted with 5,5-dimethyl-1,3-cyclohexanedione and sulfanilamide, with molecular iodine as catalyst, to give 1,8-dioxo-decahydroacridines derivatives in high to excellent yield. The structures of these compounds were established on the basis of elemental (C, H and N) and spectral analysis (¹H NMR, ¹³C NMR, MS and FTIR). All the compounds were tested for their cytotoxic activity in vitro against three human tumor cell lines: human mammary cancer cells (MCF-7), human cervical carcinoma cells (Hela), and human lung cancer cells (A549) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most of them showed moderate to potent cytotoxic activity against the tested cell lines. Among them, the most active compound 4e exhibited more efficient activity (10.92 μM) against MCF-7 cells than cisplatin (11.06 μM).     

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.     

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, ¹H-NMR, ¹³C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC₅₀ value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.     

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.     

Synthesis,spectroscopic characterization,antineoplastic, in vitro-cytotoxic,and antibacterial activities of mononuclear ruthenium(II) complexes

The synthesis, antineoplastic, cytotoxic, and antibacterial activities of Ru(II) complexes derived from quinazoline and thiosemicarbazone ligands are reported. These complexes have been prepared and characterized by UV-Vis, IR, ¹H-NMR, FAB-mass spectroscopy, and elemental analysis. The ligands and resulting complexes were subjected to in vivo antineoplastic activity against a transplantable murine tumor cell line Ehrlich ascites carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C₈, CEM, and murine tumor cell line L 1210. The ruthenium complexes show promising biological activity especially in decreasing tumor volume and viable ascitic cell counts. These complexes prolonged the life span of mice bearing EAC tumors by 10–52%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.29 to 2.9?µmol?L^?1 against Molt 4/C₈, 0.22 to 2.1?µmol?L^?1 against CEM and 0.42 to 4.7?µmol?L^?1 against L1210 cell proliferation, depending on the nature of the compound. The metal complexes are more active than the parent ligand and exhibit mild to moderate antibacterial activity.     

Cytotoxic compounds from Polygala vulgaris

To search for antitumor agents from plants, we studied Polygala vulgaris since cytotoxic lignans are known to occur in some Polygala species. Preliminary data on plant petrol ether, chloroform, and methanol extracts from the roots and aerial parts, showed in vitro cytotoxic activity against the solid tumor LoVo cell line. Fractionation of the active extracts led to the isolation of three new compounds, a derivative of aucuparine and two xanthones, as well as a known methylsinapate. All compounds were tested for in vitro cytotoxic activity using two cell lines, LoVo and its strain, which express resistance to common antitumor agents.     

Forsskamide,a new ceramide from aerial parts of Forsskaolea tenacissima Linn.

Although the various folk medicine uses and the biological activity of Forsskaolea tenacissima L., few chemical constituents of this plant have been reported, this provoked us to make our study. Forsskamide, a new ceramide was isolated from aerial parts of F. tenacissima L. (Urticaceae). The chemical structure was established by different spectroscopic methods (¹H, ¹³C-NMR, HMBC, HSQC, ROESY, FAB-MS and HR-FAB-MS). Forsskamide showed a moderate cytotoxic activity by (MTT) method against human colorectal carcinoma cell line (HCT-116) with IC₅₀ 33.25 μM in comparison with 5-fluorouracil IC₅₀ 26.42 μM. While, it did not show any activity against human hepatocarcinaoma cell line (HepG-2).     

Synthesis,spectroscopic characterization,biological screening and in vitro cytotoxic studies of 4‐methyl‐3‐thiosemicarbazone derived Schiff bases and their Co (II), Ni (II), Cu (II) and Zn (II) complexes

A series of twenty compounds inclusive of bidentate Schiff bases derived from condensation of 4‐methyl‐3‐thiosemicarbazide with substituted derivatives of napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II), Ni (II), Cu (II) and Zn (II) complexes in molar ratio (1:1) were synthesized and characterized. The coordination behavior, modes of bonding and overall geometry of the compounds was known from the elemental analysis, spectral techniques (IR, UV–Vis, ¹H NMR, ¹³C NMR, ESR and ESI‐mass), magnetic moment measurements, molar conductance, thermal and powder XRD studies. The studies revealed octahedral geometry for all the complexes where ligands coordinated in a neutral bidentate manner (NS) via nitrogen atom of azomethine group and sulphur atom of thione group with the metal centre. In vitro biological effects of the compounds were tested against four bacterial species and two fungal strains. The results indicated that the metal complexes showed a marked enhancement in biocidal activity in comparable with the parent Schiff bases. In vitro anticancer activity against the malignant tumor cell lines; human alveolar adenocarcinoma epithelial cell line (A549), human breast adenocarcinoma cell line (MCF7), human prostate cancer cell line (DU145) and human normal lung cell line (MRC‐5) using MTT assay, exposed compound 16 as a leading member with lowest IC₅₀ value of 10.6 ± 0.14 μM against (A549) cell line.     

Synthesis,characterization, antitumor,and cytotoxic activity of mononuclear Ru(II) complexes

In the search for antitumor active metal complexes several ruthenium complexes have been reported to be promising. A series of mononuclear Ru(II) complexes, [Ru(T)₂(S)]²⁺, where T?=?2,2′-bipyridine/1,10-phenanthroline and S?=?CH₃-bitsz, Cl-bitsz, Br-bitsz, tmtsz, dmtsz, have been prepared and characterized by UV-Vis, IR, ¹H-NMR, FAB-mass spectroscopy, and elemental analysis. The complexes were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's ascitic carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C₈, CEM, and murine tumor cell line L1210. Ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascitic cell counts. Treatment with these complexes prolonged the life span of EAC-tumor-bearing mice by 10–48%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24?µmol?L^?1 against Molt 4/C₈, 0.16–19?µmol?L^?1 against CEM, and 0.75–32?µmol?L^?1 against L1210 cell proliferation, depending on the nature of the compound.     

New macrocyclic diterpenes from Euphorbia connata Boiss. with cytotoxic activities on human breast cancer cell lines

Acetone:chloroform (1:2) extract of the aerial parts of Euphorbia connata Boiss. (Euphorbiaceae) was investigated for its diterpenoids. This led to the isolation of one known and two new diterpenes, belonging to the pentahydroxy-13(17)-epoxy-8,10(18)-myrsinadiene and tetrahydroxy-5,6-epoxy-14-oxo-jatropha-11(E)-ene classes. The structures were elucidated based on ¹³C and ¹H NMR as well as 2D NMR, IR and MS spectra and the cytotoxicity for compounds 1–3 were evaluated by using MTT assay against two human breast cancer cell lines. Myrsinane-type compounds – 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (1) and 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (2) – exhibited moderate inhibitory effects, with IC₅₀ values of 24.53 ± 3.39 and 26.67 ± 1.41 μM against the MDA-MB cell line, and 37.73 ± 3.41 and 34.57 ± 2.12 μM against the MCF-7 cell line, respectively. Jatrophane-type diterpene – 5,6-epoxy-8,9,15-triacetyl-3-benzoyl-14-oxo-jatropha-11(E)-ene (3) – showed weak cytotoxicity, with IC₅₀ values of 55.67 ± 7.09 μM against MDA-MB, and moderate cytotoxicity with IC₅₀ values of 24.33 ± 3.21 μM against MCF-7 cell line.     

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae)

Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4’-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC₅₀ values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).     

β-Lactam derivatives as potential anti-cancer compounds

A number of 1,4-diaryl-3-methylene substituted β-lactams, the addition products obtained from their reactions with N-, S-, and C-nucleophiles, and diverse related compounds were prepared, and a selection of 43 compounds was screened in preliminary tests as anti-tumor compounds by using 4 or 5 human cancer cell lines of diverse origins. Twelve compounds were highly active against all cell lines, 6 showed low activity, 12 no activity, and 13 exhibited a selective activity against a human small cell lung carcinoma cell line.     

Synthesis of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitriles: in vitro anticancer activity against MCF-7, PC-3 and A2780 cancer cell lines

A series of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitrile (2–9) were designed and synthesized to develop new cancer drugs. The structures of synthesized compounds 2–9 were described by using melting point, mass (MALDI-TOF-MS), FT-IR, elemental analysis, ¹H, ¹³C, ¹³C-APT and 2D NMR spectroscopy. The in vitro anticancer activities of 2–9 against human breast cancer (MCF-7), human prostate cancer (PC-3) and human ovarian cancer cells (A2780) were investigated by [3-(4,5-dimethylthiazol)-2-yl]-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assay method. Additionally, the LogIC₅₀ values of these compounds on A2780, MCF-7 and PC-3 cell lines were calculated by using inhibition % values by the GraphPad Prism 6 program on a computer. The results indicated that these compounds have high anticancer activity against MCF-7, PC-3 and A2780 cell lines (especially A2780 cell lines, p < 0.05).     

Composition,antibacterial, antioxidant and antiproliferative activities of essential oils from three Origanum species growing wild in Lebanon and Greece

The essential oils from Origanum dictamnus, Origanum libanoticum and Origanum microphyllum were analysed by GC-MS, finding carvacrol, p-cymene, linalool, γ-terpinene and terpinen-4-ol as major components. The antioxidant activity by the DPPH and FRAP tests and the antiproliferative activity against two human cancer cell lines, LoVo and HepG2, were investigated, showing that the essential oil of O. dictamnus was statistically the most inhibitory on both the cell lines, while all the oils exerted a weak antioxidant activity. Furthermore, the samples were tested against 10 Gram-negative and Gram-positive bacteria; all the oils were active on Gram-positive bacteria but O. dictamnus essential oil was the most effective (MIC = 25–50 μg/mL), showing also a good activity against the Gram-negative Escherichia coli (MIC = 50 μg/mL). Data suggest that these essential oils and particularly O. dictamnus oil could be used as valuable new flavours with functional properties for food or nutraceutical products.     

Design and anti-tumor evaluation of new platinum(II) and copper(II) complexes of nitrogen compounds containing selenium moieties

Three ligands containing selenium were synthesized by refluxing 3-acetylcoumarin (AC), 3-acetylbenzocoumarin (ABC) and acetobenzylsulfonamide (ABS) with selenosemicarbazide. The synthesized ligands were reacted with two metal salts namely; copper(II) nitrate and potassium teterachloroplatinate(II). The obtained copper and platinium complexes were characterized by different spectroscopic techniques including, ¹H NMR, ¹³C NMR, IR, UV–visible, ESR and MS. The biological activity of newly synthesized compounds were evaluated using different testes like in-vitro antimicrobial screening, anticancer, glutathione-S-transferase and Catalase activities. The in-vitro cytotoxicity against human breast cancer cell line (MCF-7), human liver cancer cell line (HepG-2) and human colon cancer cell line (HCT-116) and Human normal melanocytes (HFB 4) was investigated, where some of the tested compounds were equipotent, while the others were more potent compared with 5-flurouracil and cis-platin as reference drugs. The obtanined results showed that the best results were for copper(II) complexes and especially for benzocoumarin ligand.     

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.     

The Antiproliferative and Apoptotic Effect of a Novel Synthesized S-Triazine Dipeptide Series,and Toxicity Screening in Zebrafish Embryos

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC₅₀ values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.