A new series of titanocene dichloride derivatives bearing cyclic alkylammonium groups: Assessment of their cytotoxic properties

Ten new water soluble titanocene dichloride derivatives have been synthesized and characterized and their cytotoxicities against the human lung cancer cell line A549 have been assessed. The potencies of the compounds vary greatly, but dicationic 3-picolylium and 4-picolylium compounds exhibit IC₅₀ values that are unusually low for this class of compounds. In view of their potency against A549 cells, three of the new complexes were tested further on additional human cell lines including the small cell lung cancer cell line H69, the widely used cervical carcinoma cell line HeLa, the ovarian carcinoma cell line A2780 and its cisplatin resistant derivative A2780/CP. All three compounds exhibited potencies in all cell lines comparable to or better than those observed with the A549 cells, while one complex is actually more potent than cisplatin for HeLa cells.     

Antitumor,cytotoxic, and antioxidant evaluation of six heterocyclic compounds containing different heterocycle moieties

Heterocyclic compounds with different heterocycle moieties, namely benzoxazinone, benzimidazole, quinazolinone, and benzofuranone heterocyclic rings, were synthesized, characterized, and evaluated for their anticancer activity against human hepatocellular carcinoma cell line (HepG2) using sulforhodamine B (SRB) and dimethylthiazol-diphenyltetrazolium bromide (MTT) assays. Also, their cytotoxic activities were tested against human epithelioid carcinoma (Hela) cell line in comparison with normal cell, amniotic epithelial (WISH) cell line, as an in vitro toxicity estimation model. The results showed clearly that 2-(2-benzyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide 4 is the most potent antioxidant and anticancer agents. Although, 3-amino-2-benzylquinazolin-4(3H)-one 5 is less potent anticancer agent against Hela but it is more safe against normal cell (WISH).     

聚乙烯胺类修饰萘酰亚胺衍生物的合成、DNA键合行为和活性研究

合成了二乙烯三胺、三乙烯四胺和四乙烯五胺等低分子量聚乙烯胺类修饰的萘酰亚胺衍生物.通过UV-Vis谱、荧光光谱、圆二色谱和热变性试验研究了合成化合物与小牛胸腺DNA的键合行为,同时通过四甲基偶氮唑蓝(MTT)染色法研究了化合物对Bel-7402(人肝癌细胞)、HL-60(白血病细胞)、A549(人肺癌细胞)和Hela(人宫颈癌细胞)等细胞株的体外抗肿瘤活性,化合物NI1对A549细胞显示良好的抑制活性,优于阳性对照顺铂.     

支链/环链烷氧基乙酸为离去配体的铂(Ⅱ)配合物的体外活性研究

合成了12个带支链/环链烷氧基乙酸为离去基团的顺铂类配合物,通过元素分析、红外光谱、核磁共振氢谱和质谱对配合物进行了表征。研究了所有化合物对人非小细胞肺癌A549、人肝癌细胞BEL-7402和人乳腺癌细胞MCF-7细胞系的体外抗肿瘤活性。测试结果表明,12个配合物中有5个对人乳腺癌细胞系MCF-7有较好的体外活性。其中化合物2(顺-二(异丙氧基乙酸根)·二氨合铂(Ⅱ))在所有的化合物中显示最高的活性,对所测3个细胞系都是如此。     

一种具有抗肿瘤活性胆酸衍生物的合成新方法

以胆酸为原料, 使之与甲醇反应, 得到胆酸甲酯(2). 2采用PCC(氯铬酸吡啶)氧化得到脱氢胆酸甲酯(3), 3在CoCl2存在的条件下通过NaBH4的化学选择性还原得到7α-羟基-3,12-二氧代胆酸甲酯(4). 对4的抗肿瘤活性试验表明该化合物对Sk-Hep-1(肝癌)和H-292(肺癌)细胞株具有中等程度的细胞毒性.     

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 and Biological Activities of 1‐Azaaurone Derivatives

A series of 1‐azaaurone derivatives were designed and synthesized from 3,5‐dimethoxyaniline and 2‐chloroacetonitrile. Their structures were characterized by melting point, ¹H NMR, IR, and elemental analysis, as well as ¹³C NMR. The target compounds were evaluated for antitumor activities against human hepatocellular liver carcinoma cell line (HepG‐2) and human cervix carcinoma cell line (Hela) using methyl thiazolyl tetrazolium method. The results revealed that several 1‐azaaurones exhibited strong proliferation inhibition efficacy against HepG‐2 and Hela with an IC₅₀ range of 5.6–8.8 μg/mL without damaging normal cell.     

Ultrasonic green synthesis of silver nanoparticles mediated by Pectin: Characterization and evaluation of the cytotoxicity,antioxidant, and colorectal carcinoma properties

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of Ag nanoparticles by pectin as a natural reducing and stabilizing agent without using any toxic and harmful reagent. The biosynthesized Pectin/Ag NPs were characterized by advanced physicochemical techniques like ultraviolet–visible (UV–Vis), Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), High-Resolution Transmission Electron Microscopy (HR-TEM), Energy Dispersive X-ray spectroscopy (EDX), and X-ray Diffraction (XRD) study. It has been established that pectin-stabilized silver nanoparticles have a spherical shape with a mean diameter from 15 to 20 nm. After that, the biological performance of those biomolecules functionalized Ag NPs was investigated. In the MTT assay, human colorectal carcinoma (HCT-8 [HRT-18], Ramos.2G6.4C10, HT-29, and HCT 116) and normal cell lines (HUVEC) were used to study the cytotoxicity and anticancer potential of human colorectal over the AgNO₃ and Pectin/Ag NPs. The cell viability of Pectin/Ag NPs was very low against human colorectal carcinoma cell lines without any cytotoxicity on the normal (HUVEC) cell line. The best anti-human colorectal carcinoma properties of Pectin/Ag NPs against the above cell lines was in the case of the HCT 116 cell line. The antioxidant properties of the AgNO₃ and Pectin/Ag NPs were calculated against DPPH free radicals. The IC50 of Pectin/Ag NPs was 167 µg/mL. According to the above results, the Pectin/Ag NPs may be administrated to treat human colorectal carcinoma in humans.     

Synthesis of chalcones with anticancer activities

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC?? values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.     

Fluorescent Probes of the Apoptolidins and their Utility in Cellular Localization Studies

Apoptolidin A has been described among the top 0.1 % most‐cell‐selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20‐membered macrolide with mono‐ and disaccharide moieties. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM ) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analogue of apoptolidin A, displayed sub‐micromolar activity against H292 lung carcinoma cells. Selective esterification of apoptolidins A and H with 5‐azidopentanoic acid afforded azido‐functionalized derivatives of potency equal to that of the parent macrolide. They also underwent strain‐promoted alkyne–azido cycloaddition reactions to provide access to fluorescent and biotin‐functionalized probes. Microscopy studies demonstrate apoptolidins A and H localize in the mitochondria of H292 human lung carcinoma cells.     

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. Correspondence: Hans-Hartwig Otto, Department of Pharmaceutical/Medicinal Chemistry (PMC), Institute of Pharmacy, Ernst-Moritz-Arndt-University, 17487 Greifswald, Germany.     

Synthesis of chitosan-stabilized copper nanoparticles (CS-Cu NPs): Its catalytic activity for C-N and C-O cross-coupling reactions and treatment of bladder cancer

Herein, we report the synthesis of copper nanoparticles at ambient conditions using biopolymer, chitosan, as a protecting and stabilizing agent and hydrazine as a reducing agent. The obtained nanoparticles (CS-Cu NPs) were characterized using XRD, FT-IR, FE-SEM, EDS, TEM and UV–Vis spectroscopy. This nanocomposite was utilized as an efficient heterogeneous nanocatalyst for the aryl and heteroaryl C–N and C–O cross coupling reactions with excellent yields at mild conditions. The nanocatalyst were isolated and reused for 10 times with reproducible catalytic activity. Cell viability of nanocomposite was very low against bladder cancer (UM-UC-3 (Transitional cell carcinoma), SCaBER (Squamous cell carcinoma), and TCCSUP (Grade IV, transitional cell carcinoma)) cell lines without any cytotoxicity on the normal cell line. The best anti-human bladder cancer properties of nanocomposite against the above cell lines was in the case of TCCSUP cell line. According to the above findings, the nanocomposite may be administrated for the treatment of several types of human bladder cancer in humans.     

Tailoring of novel biologically active molecules based on N4-substituted sulfonamides bearing thiazole moiety exhibiting unique multi-addressable biological potentials

Nowadays, the growth of drug-resistant microbial strains (MDRs) is a serious public health threat worldwide. Moreover, tens of millions of people are annually diagnosed with cancer worldwide, and more than half of patients ultimately die. In the present study, a new series of 2-(4-substituted-thiazol-2-ylamino)acetamides and N-(4-substituted-thiazol-2-yl)acetamides incorporating sulfonamide moieties were designed, synthesized, well-characterized and successfully evaluated for their antimicrobial activity against multidrug resistant strains and screened for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines. Fluorescence-activated cell sorting (FACS) analysis and molecular modeling study were performed to identify the mode of action of the novel synthesized compounds and their binding interactions with the active sites of dihydrofolate reductase enzyme (DHFR).     

Antitumor activity of carboplatin in the composition of a copolymer of lactic and glycolic acids

Polymer particles containing carboplatin (CPt) were developed by the inclusion of this antitumor agent in a copolymer of lactic and glycolic acids (PLGA-COOH 50/50). The polymer particles were found to have a spherical form with an average diameter not exceeding 200 nm, the ζ-potential is equal to–32.2±1 mV. The CPt-loaded polymer particles possess a cytotoxic activity against human small cell and non-small cell lung carcinoma (lines H69 and A549), as well as against mouse mammary adenocarcinoma (line Ca755). The results of the in vivo studies carried out on female mice of line C₅₇Bl/6 with inoculated mouse melanoma of line B16 showed increasing of lifespan of the animals and inhibition of tumor growth for groups treated with the polymer particles, as compared to the animals treated with the drug substance CPt.     

Evaluation of the bioactivity of novel spiroisoxazoline typecompounds against normal and cancer cell lines

The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease.     

Some divalent metal(II) complexes of salicylaldehyde‐derived Schiff bases: Synthesis,spectroscopic characterization,antimicrobial and in vitro anticancer studies

Mononuclear transition metal(II) complexes of the type M(L)₂?2H₂O (where M = Co, Ni, Cu, Zn) have been synthesized from uninegative Schiff base ligands (HL₁–HL₄) designed by condensation of 4‐fluorobenzylamine with 2‐hydroxy‐1‐naphthaldehyde/3,5‐dichlorosalicylaldehyde/3,5‐dibromosalicylaldehyde/3‐bromo‐5‐chlorosalicylaldehyde. The compounds were successfully characterized using spectroscopic and physiochemical methods together with elemental analysis. Spectroscopic elucidation indicates a monobasic bidentate nature of ligands coordinated via deprotonated phenolic oxygen and azomethine nitrogen atom which suggests an octahedral geometry around the central metal ions. The complexes and ligands were screened for their in vitro antimicrobial activity against bacterial and fungal strains, the zinc(II) complexes being more active against the tested microbial strains. Further, the metal complexes were found to be more active than the uncomplexed ligands due to chelation process and, moreover, the complexes were more active against fungal strains than bacterial strains. Cytotoxic activities of all compounds were evaluated towards human alveolar adenocarcinoma epithelial cell line (A549), human breast adenocarcinoma cell line (MCF7), human prostate cancer cell line (DU145) and one normal human lung cell line (MRC‐5) using MTT colorimetric assay with doxorubicin as a standard. The zinc complexes were most active against the cancer cell lines and also found to be less toxic against MRC‐5 normal cell line than standard doxorubicin.     

Design and chemical behavior of novel pyrimidine derivatives and their evaluation of cytotoxicity

Abstract

Diphenyl-4-thioxo-1,4-dihydropyrimidin-5-yl)ethan-1-one 4 was obtained upon the reaction of (phenylamino)but-2-enethioyl)benzamide 3 with sodium hydroxide. The reactions of 4 with several active species such as benzaldehyde, urea, malononitrile, ethyl cyanoacetate, hydrazine, and carbon disulfide were studied. The antitumor activities of some selective compounds were examined against two cell lines: Mammalian cell lines: A-549 cells (human lung cancer cell line) and MRC-5 cells (normal human lung fibroblast cell line); some of the compounds were highly efficient; compound 13 has the most effective anticancer activity.     

Design,Synthesis and Antitumor Activity of Novel Indolin-2-one Derivatives Containing 4-Thiazolidinone Moiety

A series of novel indolin-2-one derivatives containing 4-thiazolidinone moiety(7a―7r) were synthesized and evaluated for their in vitro antitumour activities against MDA-MB-231(human breast cancer), H460(human lung cancer) and HT-29(human colon cancer) cell lines by standard 3-(4,5-dimethylthiazae-2-yl)-2,5-diphenyltetrazo- lium bromide(MTT) assay. Representative compounds(7d, 7k, 7m, 7p) with higher cytotoxicity were further examined against one normal cell line(WI-38, human fetal lung fibroblasts). The preliminary investigation shows that most of the compounds display moderate to excellent potency and high selectivity against different human cancer cell lines. In particular, the most potent compound 7m shows promising cytotoxicity against MDA-MB-231, H460 and HT-29 cell lines with IC₅₀ values of 0.78, 0.056 and 0.018 μmol/L, respectively. The potency is much higher than that of Sunitinib(IC₅₀=3.46 μmol/L against MDA-MB-231, IC₅₀=2.59 μmol/L against H460, IC₅₀=1.50 μmol/L against HT-29) by 4.4, 46.3 and 83.3 fold.     

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.     

Citrus sinensis leaf aqueous extract green-synthesized silver nanoparticles: Characterization and cytotoxicity,antioxidant, and anti-human lung carcinoma effects

The present work demonstrates the synthesis of Ag nanoparticles (Ag NPs) by using aqueous extract of Citrus sinensis as green reductant and capping agent without any toxic reagent. Physicochemical characteristics of the said nanoparticles were elucidated by field emission scanning electron microscopy (FESEM), fourier transform infrared spectroscopy (FTIR), and ultraviolet–visible spectroscopy (UV-Vids) techniques. The biogenic Ag NPs are uniformly globular. The Ag NPs has been explored biologically in the anticancer and antioxidant assays. In the cellular and molecular part of the recent study, the treated cells with Ag NPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung carcinoma properties on normal (HUVEC) and lung carcinoma cell lines i.e. NCI-H661, HLC-1, NCI-H1563, LC-2/ad, NCI-H1299, and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of Ag NPs. The IC50 of Ag NPs were 82, 139, 170, 66, 62, and 50 µg/mL against NCI-H661, HLC-1, NCI-H1563, LC-2/ad, NCI-H1299, and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of Ag NPs and vitamin E against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals were 21 and 15 µg/mL, respectively. After clinical study, Ag NPs containing Citrus sinensis leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat the several types of human lung adenocarcinoma.