Design,Synthesis and Antiproliferative Activities of Diaryl Thiourea Derivatives as Anticancer Agents

Two new series of diaryl thiourea containing sorafenib derivatives 9a – 9t were designed and synthesized, and their antiproliferative activities against PC‐3, HCT116 and MDA‐MB‐231 cell lines were evaluated. All compounds generally showed antiproliferative activity to PC‐3 cells, most of the analogs exhibited potent antiproliferative activity to HCT116 cells, and compounds 9e , 9f , 9o and 9p demonstrated inhibitory activities against all three cell lines. The structures of all the newly synthesized compounds were determined by ¹H NMR, ¹³C NMR and HRMS.     

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 IC values of 0.13 mmol/L,0.7 mmol/L and 0.5 mmol/L,respectively.     

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.     

Studies on the Synthesis and Antiproliferative Activities of 13‐cis‐Retinoyl Sugar Derivatives

New retinoyl sugar derivatives of 13‐cis‐retinoic acid were synthesized in three ways in this paper in order to enhance pharmacal effects, especially antiproliferative activities of 13‐cis‐retinoic acid. Their structures were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, and MS spectra and their antiproliferative activities were determined in vitro using human cancer lines. Results showed that some compounds possessed potential antitumor activities.     

β-榄香烯聚乙二醇衍生物的合成及体外抗癌活性

以中草药有效成分β-榄香烯为起始原料, 在碱性条件下与氨基化的聚乙二醇(PEG)反应合成了一系列β-榄香烯单取代PEG衍生物, 利用IR, ¹H NMR及¹³C NMR对其结构进行了表征. 并采用WST-1法观察其对人宫颈癌细胞(Hela)、人白血病细胞(K562)的抑制作用, 探讨其体外抗肿瘤活性. 细胞实验结果表明经PEG修饰的β-榄香烯的抗癌活性有不同程度的增强.     

Design,synthesis, and characterization of some new benzimidazole derivatives and biological evaluation

A new series of benzimidazole derivatives ( 1-15 ) containing 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole, and thiazolidinon rings have been synthesized. All new synthesized benzimidazole compounds were confirmed by ¹H NMR, ¹³C NMR spectra, and LC-MS, and they were examined for their antioxidant and antimicrobial activities. Compounds 7 and 1 showed the highest and the lowest antioxidant activities, respectively. The lowest minimum inhibition concentration value found in compound 5 against Enterobacter aerogenes.     

Synthesis and in vitro cytotoxic activities of sorafenib derivatives

A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively.     

Synthesis and Biological Activities of 6‐Hydroxyaurone Derivatives

A series of 6‐hydroxyaurone derivatives were synthesized in satisfactory yields and characterized by IR, ¹H NMR, ¹³C NMR, and HRMS or elemental analysis. The structure of compound 3e was further confirmed by X‐ray crystal analysis. Bioassay results indicated that some of the target compounds displayed moderate herbicidal activity against the dicotyledonous plant Brassica campestris L. at 100 µg·mL^?1, and some compounds also showed significant antiproliferative activity against tumor cell lines Hela, HepG‐2, and MCF‐7.     

嘌呤磺胺衍生物的合成及抗肿瘤活性

合成了一系列结构全新的嘌呤磺胺类衍生物, 并应用溴化噻唑蓝四氮唑(MTT)法进行了初步体外抗肿瘤细胞增殖活性研究. 结果表明, 嘌呤环C2位、 N6位和N9位的取代对活性均有较大影响, C2位引入苯磺酰基哌嗪片段后有利于提高抗肿瘤活性. 化合物17d对3株肿瘤细胞PC-3, HCT116和K562 的增殖均有明显抑制作用, 且强度与阳性对照药Roscovitine相近.     

Synthesis and biological activity of novel N-substituted 4-amino-6,7,8-trimethoxyquinazoline compounds

A series of N-substituted 4-amino-6,7,8-trimethoxyquinazoline derivatives has been synthesized from 4-chloro-6,7,8-trimethoxyquinazoline and aryl (or benzyl) amines using 2-propanol as a solvent. The starting material 4-chloro-6,7,8-trimethoxyquinazoline has been synthesized from natural gallic acid by a novel route. Their structures have been verified by elemental analysis and IR, ¹H, and ¹³C NMR spectroscopy. The title compounds have been evaluated for their in vitro antiproliferative activities against some cancer cells by the MTT method. Unfortunately, most of the compounds tested have exhibited a weaker anticancer activity than the reference standard drug PD153035. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1521–1531, September, 2007.     

Egyptian herbal tea infusions' antioxidants and their antiproliferative and cytotoxic activities against cancer cells

The antioxidant, antiproliferative and cytotoxic activities against different human cancer cells were investigated in local and recently introduced plants of Mentha sp., Rosmarinus officinalis L. (ROL) and Origanum majorana L. (OML). ROL exhibited the highest antioxidant activities (IC₅₀ 8.4 ± 0.2 μg/mL) followed by OML and mint species such as Mentha suaveolens ‘apple mint’ and Mentha longifolia L. exhibiting moderate antioxidant activities. HPLC analysis of leaf extract revealed that rosmarinic acid is the main component followed by caffeic acid. Herbal leaf extracts varied in their proliferation inhibition and cytotoxicity against HeLa, MCF-7 and Jurkat cancer cells in a dose-dependent matter. The highest antiproliferative inhibition and cytotoxic activity were detected in ROL and OML followed by mint. Local herbs might have a potential role as anticancer natural medicines in addition to their high antioxidant activities due to the presence of different phenolics in their aqueous tea extracts.     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of Imidazolone Fused Pyrazolo[1,5‐a]pyrimidine Derivatives

A novel series of imidazolone fused pyrazolo[1,5‐a]pyrimidine derivatives has been designed and synthesized using a convergent approach, and the structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. These new compounds were tested for their in vitro antiproliferative activity using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Out of the 20 derivatives prepared in the current study, compounds 8h , 8n , and 8r exhibited good anticancer activities tested against HeLa cells and HepG₂ cells. However, the in vitro anticancer activity of compound 8r against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs Paclitaxel and SAHA.     

Synthesis of Hydroxypropyltrimethyl Ammonium Chitosan Derivatives Bearing Thioctate and the Potential for Antioxidant Application

Hydroxypropyltrimethyl ammonium chloride chitosan (HACC) is one of the most important water-soluble chitosan derivatives; its derivatives have gained growing attention due to their potential biomedical applications. Here, hydroxypropyltrimethyl ammonium chitosan derivatives bearing thioctate (HACTs), with different degrees of substitution of thioctate, were prepared using HACC and α-lipoic acid as the reaction precursors, using an ion exchange method. The structural characteristics of the synthesized derivatives were confirmed by FTIR, ¹H NMR, and ¹³C NMR spectroscopy. In addition, their antioxidant behaviors were also investigated in vitro by the assays of reducing power, and scavenging activities against hydroxyl radicals and DPPH radicals. The antioxidant assay indicated that HACTs displayed strong antioxidant activity compared with HACC, especially in terms of reducing power. Besides, the antioxidant activities of the prepared products were further enhanced with the increase in the test concentration and the degrees of substitution of thioctate. At the maximum test concentration of 1.60 mg/mL, the absorbance value at 700 nm of HACTs, under the test conditions, was 4.346 ± 0.296, while the absorbance value of HACC was 0.041 ± 0.007. The aforementioned results support the use of HACTs as antioxidant biomaterials in food and the biomedical field.     

Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazolethione and its triazolium derivatives displayed the most potent activities against all the tested strains.     

Design,Synthesis, Inhibiting HDACs Ability and Antitumor Activity of Pyrimidin-4(3H)-one Hydroxamate Derivatives

A series of novel pyrimidin-4(3H)-one hydroxamate derivatives was designed, synthesized and studied for their activities against histone deacetylases(HDACs). The results indicate that all the compounds show HDACs inhibitiory activity. The antiproliferative activities of the compounds against HeLa and A549 cells were also investigated. The pharmacological results show compound 9g has potent activity in the enzymatic inhibition assay and cell-based 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 1h (with IC_(50) values of 5.2μmol/L and 1.9μmol/L against Bel-7402 and HT-1080,respectively).The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.     

An Efficient Synthesis of Chromeno[4,3‐d]isoxazolo[5,4‐b]pyridin‐6‐one Derivatives

A series of chromeno[4,3‐d]isoxazolo[5,4‐b]pyridin‐6‐one derivatives were easily and efficiently synthesized by the reaction of 3‐acyl‐2H‐chromen‐2‐ones with isoxazol‐5‐amine in acetic acid. Some synthesized compounds were evaluated for their antiproliferative properties in vitro against cancer cells, and these compounds were found to have some activities.     

Synthesis,Antiproliferative Activity and Radical Scavenging Ability of 5-O-Acyl Derivatives of Quercetin

Quercetin is a flavonoid that is found in many plant materials, including commonly eaten fruits and vegetables. The compound is well known for its wide range of biological activities. In this study, 5-O-acyl derivatives of quercetin were synthesised and assessed for their antiproliferative activity against the HCT116 colon cancer and MDA-MB-231 breast cancer cell lines; and their radical scavenging activity against the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical species. Four derivatives were found to have improved the antiproliferative activity compared to quercetin whilst retaining radical scavenging activity.     

Novel 5‐Methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐ 3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole Derivatives: Synthesis and Anticancer Activity

Eleven novel 5‐methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole derivatives were synthesized and characterized by elemental analysis, ESI‐MS, ¹H NMR and ¹³C NMR. All of the compounds have been screened for their antiproliferative activities against PC‐3 cell (human prostate cancer) and A431 cell (human epidermoid carcinoma cancer) lines in vitro. The results revealed that compounds 4g , 4j and 4k exhibited the strong inhibitory activities against the PC‐3 cell lines (with IC₅₀ values of 2.8±0.11, 3.1±0.10 and 3.0±0.06 μg/mL, respectively).     

Synthesis and antiproliferative evaluation of some novel quinazolin-4(3H)-one derivatives

A series of novel quinazolinone derivatives was designed and synthesized. The antiproliferative activities were evaluated in vitro using MTT assay against hepatocellular carcinoma (HepG-2) and mammary gland breast cancer (MCF-7). The preliminary bioassay results demonstrated that tested compounds exhibited antiproliferation with various degrees. Triazole moiety enhanced the activity against the two cell lines when incorporating with quinazolinone moiety in a single molecular framework. Acetohydrazide-quinazolinone derivative showed strong activity against the two cancer cells comparable to that of doxorubicin. Biological evaluation indicated that all the tested compounds possessed antiproliferative activity with certain degrees.