Gold-catalyzed oxazoles synthesis and their relevant antiproliferative activities

Nine 5-aryl-2-methyloxazole derivatives were synthesized via gold-catalyzed alkyne oxidation. All of the compounds have been screened for their antiproliferative activities against MCF-7 cell （human breast carcinoma）, A549 cell （human lung carcinoma） and Hela cell （human cervical carcinoma） lines in vitro. The results revealed that compounds 1b, 1c and 1d exhibited strong inhibitory activities against the MCF-7 cell lines （with ICso values of 4.6, 9.7 and 2.2 μmol/L, respectively）.     

Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis,Cytotoxicity, and Molecular Docking

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC₅₀ values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.     

Design and synthesis of alepterolic acid and 5-fluorouracil conjugates as potential anticancer agents

Conjugates of alepterolic acid with 5-fluorouracil derivatives have been synthesized in 70–90% yields. The cytotoxic evaluation against two human cancer cell lines, viz. MCF-7 (breast) and A549 (lung), using MTT assay showed anticancer activities of the obtained compounds.     

Green synthesis of some tetrahydroquinoline derivatives and evaluation as anticancer agents

This study demonstrates the design and synthesis of heterocyclic compounds with diverse biological effects. Using an ionic liquid catalyst, a sonosynthetic approach for the assembly of bis-arylidene cycloalkanone derivatives (bis-chalcones) has been reported. Three cancer cell lines Hepatocellular carcinoma cells (HepG-2), Breast carcinoma cells (MCF-7), and Lung carcinoma cells (A-549) were utilized to investigate the antiproliferative effects of some selected samples. Many evaluated drugs exhibited good to moderate cytotoxicity against the examined cell lines. Notably, the IC₅₀ values for the S-alkyl derivatives ranged from 2.86 to 13.14 µg/mL.     

Design,synthesis, and evaluation of novel combretastatin A-4 based chalcone derivatives as anticancer agents

A series of combretastatin A-4 based chalcones ( 14a-l ) were designed, synthesized and these compounds examined for inhibitory effects on the proliferation of human lung (A549), breast (MCF-7), melanoma (A375), and colon (HT-29) carcinoma cells. Compounds 14b , 14c , 14e , 14h , and 14i (tri/dimethoxy, methyl, and mono/dinitro derivatives) have exhibited the most potent antiproliferative activity with IC₅₀ < 2 μM and the hexa methoxy derivative 14b , the most promising one, which displayed the potent inhibitory activities in MCF-7 (IC₅₀: 10 nM), A375 (IC₅₀: 12 nM), and A549 (IC₅₀: 65 nM) cell lines, and is 18 times more potent than the CA-4. Compound 14b represents a new scaffold and the results provide insights into further development of anticancer agents.     

Syntheses of amamistatin fragments and determination of their HDAC and antitumor activity

[reaction: see text] Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC50 0.24-0.56 microM). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells.     

Synthesis and cytotoxic evaluation of novel brominated N-alkyl pyrano[3,2-c]quinolinones

A novel series of 6-alkyl-4-bromopyrano[3,2-c]quinoline-2,5-diones ( 2a–c ), 6-alkyl-3,4-dibromopyrano[3,2-c]quinoline-2,5-diones ( 4a–c ), and 6-alkyl-3-amino-bromopyrano[3,2-c]quinoline-2,5-diones ( 6a–c ) were synthesized via appropriate conventional methods and in good yields. The structures of target compounds were approved by elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The antitumor inhibitory activities of the new compounds were evaluated on several cancer cell lines, A-549 (human lung cancer), HCT-116 (human colon cancer), MCF-7 (breast cancer), and HePG-2 (human liver cancer). Moreover, 50% inhibitory concentrations, IC₅₀, were established. 5-Fluorouracil was used as a positive control in the viability assay. The screening results showed that most of the examined compounds exposed powerful inhibition activity toward various cell lines. Particularly, Compound 4c exhibited higher cytotoxic activity against four tumor cell lines than the reference drug, 5-fluorouracil, with significantly lower IC₅₀ values. Accordingly, most of the synthesized compounds would be a better prospective growth in the anticancer drug discovery.     

Antitumor activity of stilbenoids and flavonoids isolated from Acanthopanax brachypus

This report is the first to detail the antitumor activity of Acanthopanax brachypus, a species well recognized by eastern folk medicine. Four stilbeniods and nine flavonoids have been isolated from stem bark of the plant. The isolates have been tested for their antitumor activity against selected human cancer cell lines (HgpG-2, MCF-7, K-562, and A-549). Even though three of the compounds have shown high to moderate cytotoxicity against certain cell lines (IC₅₀ of 4.5 to 6.5 μg/mL), in most of the experiments little or no anticancer activity has been revealed.     

Benzofuran–isatin Hybrids: Design,Synthesis, and In Vitro Anti‐cancer Activities

A series of novel benzofuran–isatin hybrids 6a – s tethered through propylene and butylene were designed, synthesized, and evaluated for their in vitro anti‐cancer activities against HepG2 (liver carcinoma), Hela (cervical cancer), A549 (lung adenocarcinoma), DU145 (prostatic cancer), SKOV3 (ovarian carcinoma), MCF‐7 (breast cancer), and drug‐resistant MCF‐7/DOX (doxorubicin‐resistant MCF‐7) human cancer cell lines. The majority of the synthesized hybrids displayed weak to moderate in vitro activities against the tested seven cancer cell lines, but the enriched structure–activity relationship may pave the way for further optimization.     

Synthesis and in vitro antitumor activity of 1,3,4-thiadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-thiadiazole derivatives based on benzisoselenazolone were synthesized and evaluated for their cytotoxicity in vitro against human liver cancer cell SSMC-7721,human breast cancer cell MCF-7 and human lung cancer cell A549 by CCK-8 assay.The results showed mat compounds 7e,7f,7h,7k,71 and 7m displayed good cytotoxicity against MCF-7 cell lines.Compound 71 exhibited the most potent antitumor activities among the tested compounds.     

Design,Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC₅₀ values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.     

Synthesis and antitumor activities of novel bis-quinazolin-4(3H)-ones

With the aim of obtaining new antitumor agents, a series of bis-quinazolin-4(3H)-ones ( 3a-3 f ) were designed and synthesized. These products contain 4-oxo-1,2,3,4-tetrahydro-quinazoline and 3H-quinazolin-4-one moieties linked together via a propyl chain. Cytotoxic activities of 3a-3 f were evaluated against lung adenocarcinoma (A549), breast carcinoma (MCF-7) and ovarian cancer (SKOV3) cell lines using MTT method. Cisplatin was used as a positive control. Among the tested compounds 3a , 3b , and 3e showed the best cytotoxic activities against all cancerous cell lines with IC₅₀ values even less than cisplatin. Compounds 3d and 3f also showed desirable cytotoxic activities especially against A549 and MCF-7.     

Design,Synthesis, and Anticancer Activity of Amide Derivatives of Structurally Modified Combretastatin-A4

A new series of amide derivatives of structurally modified combretastatin-A4 10a–10j are synthesized, and their structures are confirmed by ¹H and ¹³C NMR, and mass spectral data. The products are tested for their anticancer activity towards human cancer cell lines, MCF-7 (breast), A-549 (lung), Colo-205 (colon), and A-2780 (ovarian). The compounds 10b, 10c, and 10d demonstrate the most promising activity.

     

新型[1,2,4]三唑[4,3-b]均四嗪类化合物的合成及其抗癌活性

以6-(3,5-二甲基吡唑-1-基)-3-肼基均四嗪和芳醛为原料,经Schiff碱缩合和环合反应合成了6个新型的6-芳基-3-(3,5-二甲基吡唑-1-基)[1,2,4]三唑[4,3-b]均四嗪类化合物(4a～4f),其结构经1HNMR,MS,IR和元素分析表征。以顺铂为对照,采用MTT法测试了体外4a～4f对人白血病细胞株,人肺癌,人乳腺癌和人子宫颈癌细胞株的抗癌活性。结果表明,4a～4f对四种癌细胞均具有较强的抑制活性。     

Synthesis and Biological Evaluation of Amide Derivatives of Imidazopyridine as Anticancer Agents

A series of new amide derivatives of imidazopyridine is synthesized and structures of the products are confirmed by ¹H and ¹³C NMR, and mass spectral data. The synthesized derivatives are screened for their anticancer activity against four human cancer cell lines: lung cancer (A549), breast cancer (MCF-7), melanoma cancer (A375), and colon cancer (HT-29). Six synthesized compounds exhibit more potent activity than the control drug.

     

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.     

(1iR, 1iiR, 2iR, 2iiR)-Ni, Nii-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺作为配体的双核铂配合物的合成及其抗癌活性

以(1ⁱR,1ⁱⁱR,2ⁱR,2ⁱⁱR)-Nⁱ, Nⁱⁱ-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺(HL)作为配体,设计并合成了7种双核铂配合物,并利用IR,¹H NMR,¹³C NMR,ESI-MS和元素分析等进行了表征。通过MTT法测定目标双核铂配合物对人类HepG-2,A549,HCT-116和MCF-7四种癌细胞系的细胞毒性。结果表明,所有的化合物对HepG-2,A549和HCT-116细胞系均表现了良好的细胞毒活性,但对MCF-7细胞系均无活性。其中,以3-羟基环丁烷-1,1-二羧酸为离去基团的配合物P7对HepG-2和A549细胞系的活性优于卡铂,对HCT-116细胞系的活性接近于奥沙利铂。     

Synthesis and in vitro antitumor activity of 1,3,4-oxadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-oxadiazole derivatives based on benzisoselenazolone has been prepared and tested for antiproliferative activity in vitro against the cells of human cancer cell lines: SSMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell). All the compounds obtained exhibited antiproliferative activity and showed selective cytotoxicity against different cancer cells. Compounds 7d and 7i showed significant antiproliferative activities against MCF-7 cells, with IC50 values of 1.07 and 1.76?μM respectively. Compound 7d were found to be the most potent compound against SSMC-7721 cells, with IC50 values 4.46?μM.     

Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents

In the current report, we have rationally designed a series of uracil-coumarin based bifunctional molecular hybrids roped by 1,2,3-triazole moiety. The designed compounds were synthesized and tested against a panel of six human cancer cell lines namely Colo-205, MCF-7, A-549, PA-1, PC-3 and Hela cells by Sulforhodamine B assay. The results indicated that the hybrid molecules can specifically inhibit the MCF-7 cancer cell proliferation amongst which A-2 was found to be most potent hybrid (GI₅₀ = 1.55 µM) with fluorine atom as R with two carbon chain length between triazole and coumarin moieties. Cell cycle analysis revealed that A-2 significantly arrest the G2/M phase to inhibit proliferation of MCF-7 cells. Due to its mitotic arrest, A-2 was further analyzed to predict its various binding interactions within the active site of tubulin, which revealed its best binding pattern within the vinblastine binding site. In addition to this, antibacterial potential of all the synthetics was also evaluated which resulted in two hit lead molecules A-2 (MIC = 11.7 μg/mL) and A-3 (MIC = 7.23 μg/mL) that can significantly inhibit the bacterial strain Staphylococcus aureus comparable to that of standard drug levofloxacin (MIC = 3.12 μg/mL). Binding interactions within the active site of dihydrofolate reductase (DHFR) were also streamlined by using molecular docking studies. Overall studies revealed some interesting features of synthetics to be active which stated that, the compounds with electronegative atom on R and compounds with two carbon chain length between triazole and coumarin showed best results.     

Design,Synthesis, and In Vitro Anticancer Activities of Diethylene Glycol Tethered Isatin‐1,2,3‐triazole‐coumarin Hybrids

A series of novel diethylene glycol tethered isatin‐1,2,3‐triazole‐coumarin hybrids 9a – l were designed, synthesized, and evaluated for their in vitro anticancer activities against HepG2 (liver carcinoma), Hela (cervical cancer), A549 (lung adenocarcinoma), DU145 (prostatic cancer), SKOV3 (ovarian carcinoma), MCF‐7 (breast cancer), and drug‐resistant MCF‐7/DOX (doxorubicin‐resistant MCF‐7) human cancer cell lines. The results showed that most of the synthesized hybrids exhibited considerable in vitro activities against the tested seven cancer cell lines, and these hybrids can be acted as starting points for further investigation.