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.     

3-芳基噻唑烷-4-酮-2-酰胺的合成及其抗肿瘤活性研究

合成了系列新的3-芳基噻唑烷-4-酮-2-酰胺衍生物,并测试了化合物抑制肿瘤细胞增殖活性.部分化合物对A-549和Hela肿瘤细胞有弱的细胞毒性,而对BGC-823没有抑制作用,表现出一定的选择性.其中,化合物7ad对A-549有较强的抑制活性(IC50=21.0μmol·L-1),与阳性对照顺铂的抑制活性(IC50=19.4μmol·L-1)相当.初步的构效关系表明化合物的立体结构可能对其抗肿瘤活性影响较大.     

新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性

根据活性亚结构拼接原理,通过紫罗兰酮与(取代)苯甲醛反应合成了紫罗兰酮基双查尔酮,然后经与氨基硫脲缩合得到一系列未见报道的新型含紫罗兰酮、查尔酮及氨基硫脲3种优势结构单元的杂化体,它们的化学结构经傅里叶变换红外光谱(FT-IR)、核磁共振波谱(~1H NMR、~(13)C NMR)、元素分析及质谱(MS)等测试技术所证实。采用溴化噻唑蓝四氮唑(MTT)法初步测定其体外抗肿瘤活性(乳腺癌细胞(MCF-7),肝癌细胞(Hep G2),肺癌细胞(A549)),结果表明,对于不同类型的肿瘤细胞,化合物展现较好的增殖抑制活性。尤其是化合物3a与3b对MCF-7细胞展现较强的抗增殖活性,半数致死量(IC_(50))值分别为10.83和7.62μmol/L,化合物3e对A549细胞显示一定的增殖抑制活性效果(IC_(50)值为13.36μmol/L),化合物3f对Hep G2细胞表现了高效的抗增殖活性(IC_(50)值为8.55μmol/L)。目标物的抗增殖活性与紫罗兰酮结构及查尔酮环上不同电子效应的取代基有关。     

Synthesis,characterization and anticancer activity of a series of curcuminoids and their half‐sandwich ruthenium(II) complexes

A series of curcuminoids (L¹–L⁷) and their corresponding (η⁶‐p ‐cymene)Ru^II(Cur)Cl complexes ( 1 – 7 ) were synthesized and characterized using ¹H NMR spectroscopy, elemental analysis and high‐resolution electrospray ionization mass spectrometry. The molecular structures of L², L⁴, 1 and 4 were determined using single‐crystal X‐ray diffraction analysis. The stability of 1 – 7 was investigated by monitoring their UV profiles. The compounds were further evaluated for their in vitro antiproliferative activities against the HepG2 human liver and HeLa human cervical cancer cell lines and HEK‐293 T noncancerous cell line.     

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3–11 was synthesised from 5-hydroxy-3,7,3′,4′-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC₅₀ values of 9.51–53.33 μM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4–9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.     

Synthesis,antioxidant, and anticholinesterase activities of novel N-arylsulfonyl hydrazones bearing sulfonate ester scaffold

In this research, two new series of N-arylsulfonyl hydrazone compounds ( 14 – 25 ) possessing a sulfonate moiety were synthesized and characterized by elemental analysis and various spectroscopic techniques including fourier transform infrared (FT-IR), ¹H-, and ¹³C nuclear magnetic resonance (NMR). These compounds synthesized as target molecules ( 14 – 25 ) were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities and antioxidant potential. The antioxidant capacities of the tested molecules were determined by four different assays. The IC₅₀ values of the screened molecules were determined in the range of 60.14 ± 0.25–84.81 ± 1.09 μM against AChE and in the range of 70.11 ± 0.67–93.60 ± 0.47 μM against BChE. In the AChE assay, 4-hydroxybenzaldehyde-based compound 25 (60.14 ± 0.25 μM) showed the highest activity in comparison to rivastigmine (501 ± 3.08 μM). This compound (71.42 ± 0.19 μM) is also one of the compounds with the highest activity against BChE. In the BChE assay, 2-hydroxybenzaldehyde-based compound 19 (70.11 ± 0.67 μM) indicated the highest activity in comparison to rivastigmine (19.95 ± 0.20 μM). In antioxidant activity studies, the tested molecules showed lower activities than the standard compounds (butylated hydroxytoluene and α-tocopherol). Consequently, some novel compounds can be used as potential inhibitor candidates in future studies.     

Synthesis,in vitro biological evaluation and in silico docking studies of new quinazolin-2,4-dione analogues as possible anticarcinoma agents

Today, cancer is considered as one of the major reasons of death in human beings worldwide. We reported herein the synthesis, anticancer activity, and in silico docking studies of a series of nine quinazolindione-based scaffolds bearing pyrimidine, pyridine, pyran, and pyrazole moieties ( 1 - 9 ) through Michael addition, Vilsmeier-Haack, Claisen-Schmidt, and nucleophilic addition reactions. The chemical structures of the newly prepared compounds were ascertained by means of their spectral analysis techniques like IR, ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, mass spectroscopy, and elemental analysis. This work was conducted to investigate the implication of Rho7 protein in breast and hepatocellular cancer cells aggressively. MCF-7 and HepG2 cells have been selected as models for the effect of protein expression on breast and hepatocellular cancers cell growth. All prepared compounds were biologically evaluated for their antiproliferative efficacy on hepatic cancer cell lines (HepG2) and breast cancer cell lines (MCF-7); also, their effects on normal cell lines (BALB/3T3) were studied. Moreover, in silico molecular docking studies were studied for the compounds against the binding site of Homo sapiens Rho7 protein. The pharmacokinetic properties of the newer compounds were also evaluated using various computational tools. The compounds showed interesting interactions with satisfactory docking scores to the target Rho7; thus, they may act as promising potent drug candidates against cancer.     

Synthesis,characterization, duplex-DNA interactions,and anticancer activities of novel octahedral [Ni(phen)2(dppz-idzo)]2+ and [Co(phen)2(dppz-idzo)]3+ complexes

Two new octahedral [Ni(phen)₂(dppz-idzo)]²⁺ and [Co(phen)₂(dppz-idzo)]³⁺ complexes have been synthesized and characterized by CHN analysis, electrospray ionization-MS, nuclear magnetic resonance, and UV–Vis spectra. The DNA-binding ability of these complexes was spectrophotometrically, hydrodynamically, and electrophoretically evaluated which indicated that they strongly intercalate into the DNA double helix, and that both induced severe DNA damage in the presence of peroxide. The complexes also showed strong antiproliferative effect against HepG2 and MDA-MB-231 cells. By contrast, they were found to be inactive against the MCF-7 cell line. The ligand itself was found to be inactive against the cells tested.     

Synthesis and antiproliferative activities of thioxoflavonoids on three human cancer cells

Two series of fifteen novel thioxoflavonoids 2a-2h and 4a-4g were synthesized from corresponding flavonoids 1a-1h and 3a-3g by reacting with Lawesson’s reagent, respectively. Their in vitro antiproliferative activities were evaluated on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) using cell counting kit-8 (CCK-8) assay. The results showed that most of the target compounds exhibited moderate to good antiproliferative activities against the three human cancer cell lines. In particular, thioxoflavonoids 2f and 2g showed the strongest antiproliferative activity on all three human cancer cell lines with IC₅₀ values ranging from 3.34 to 4.67 μM, 4f showed the best antiproliferative activity on Hela cells (IC₅₀ 2.30 μM), 2e showed the best antiproliferative activity on HCC1954 cells (IC₅₀ 2.13 μM) and SK-OV-3 cells (IC₅₀ 2.33 μM). The antiproliferative activities may be involved in their antioxidant activity, which can be speculated by their ability to scavenge free radicals and by their capacity of affecting key redox enzymes.     

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.     

Cyclization of N-benzyl cyanoacetamide: Novel synthesis and biological activity of pyrrole,pyrimidine, and pyran derivatives

Heteroannulation of N-Benzyl cyanoacetamide 1 to a new series of heterocycles has been developed. Thus, reaction of 1 with different polarized π systems afforded pyrrolo 4 , pyridone 6 , pyridine 8 , and diazapene 10 derivatives, respectively. N-Benzyl cyanoacetamide that undergo condensation reaction with salicylaldehyde yielded pyran derivative 11 . Nitrosation of 11 furnished condensed pyran 13 . Compound 11 reacted with benzaldehyde, carbon disulfide (cyclizing agent), and ammonium thiocyanate to provide pyrane 17 , thiazine 18 , and thiourea 20 derivatives, respectively. Cinnamoyl isothiocyanate was reacted with compound 11 to produce non-isolable thiourea derivative 21 . The newly synthesized compounds have been characterized by infrared (IR), proton nuclear magnetic resonance (¹H NMR), and carbon nuclear magnetic resonance (¹³C NMR) spectral data. The compounds were then evaluated for antibacterial and anticancer activities.     

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).     

人宫颈癌细胞(Hela)内的31P核磁共振研究

建立了无损伤性³¹P NMR研究细胞内物质的实验方法, 并对人宫颈癌细胞(Hela)的³¹P NMR谱中含磷小分子代谢物的谱峰进行了分析; 细胞内无机磷(Pi)的化学位移对pH非常敏感, 通过测定其化学位移可间接确定细胞内的pH, Hela细胞内Pi峰的化学位移为5.88±0.01 (n＝3), 计算得到细胞内 pH值为7.05±0.01; 通过测量Hela细胞的³¹P NMR谱中ATP的α磷和β磷及γ磷的化学位移差值, 得出Hela细胞内Mg^2＋与ATP结合的复合物MgATP和整个ATP量的比值, 计算得到Hela细胞内游离Mg^2＋浓度为(253.3±0.13) mmol/L (n＝3), 与其它分析方法相比, ³¹P NMR测定细胞内游离Mg^2＋浓度具有对细胞样品无损伤的优点.     

Design,Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC₅₀ = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79%) activity. Compound 4g was found to be the most active compound against EGFR (IC₅₀ = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.     

Synthesis and antitumor activities of novel 2-substituted pyrimidinone-5-carboxylic acid benzylamides

The title compounds were synthesized via N-benzylmalonamic acid methyl ester (3). As the key intermediate, 3 was prepared from methyl malonyl chloride and benzylamine. Then, compound 3 was reacted with dimethyl-formamide dimethyl acetal yielding vinylogue amides 4 and 5. Isomers 4 and 5 were respectively treated with amidine and guanidine to afford the title compounds 2-substituted pyrimidinone-5-carboxylic acid benzylamides 6 and 7. All of the new compounds were characterized by ¹H-NMR (nuclear magnetic resonance), ¹³C-NMR, MS and High Resolution Mass Spectrometer (HRMS). The antitumor activities of the compounds were tested in vitro against LoVo cells and Hep3B cells. Both compounds 6 and 7 show activity against these two cell lines. Translated from Huaxue Tongbao (Chemistry), 2006, 69(8): 623–626 (in Chinese)     

Synthesis,Crystal Structure and Anticancer Activities of Tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones

A new series of tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones ( 3a–3x ) were designed and synthesized. Their structures were confirmed by ¹H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X‐ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO‐8910 cells and liver cancer SMMC‐7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC₅₀ of them were 3.22 and 3.65 µg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5‐FU (IC₅₀=8.56 µg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase‐3/7 in leukemic K562 cells.     

Improved Antiproliferative Activities of a New Series of 1,3,4-Thiadiazole Derivatives Against Human Leukemia and Breast Cancer Cell Lines

Twenty-two novel 1,3,4-thiadiazole derivatives were synthesized using different aromatic acids as starting materials, followed by cyclization, coupling and deprotection reaction. The structures of all the target compounds were identified by means of ¹H nuclear magnetic resonance(NMR), ¹³C NMR and high resolution mass spectrometer(HRMS). Further biological evaluations were performed for chronic myelogenous leukemia cell and breast cancer cell. The results suggest that most of the target compounds exhibit potent anti-proliferative activities. Especially, compound 5b shows better antiproliferative activities against MDA-MB-231 and K562 cell lines compared with gossypol.     

硫（醇）代N-对甲苯基/苯基磺酰基氨基羧酸酯类化合物的合成与神经营养活性

根据官能团的组合,设计合成了硫（醇）代N-对甲苯基/苯基磺酰基氨基羧酸酯类化合物,这些化合物的结构¹H NMR, ¹³C NMR, MS 和 HRMS证实,初步的实验结果表明：在10μg/mL浓度下,化合物4a, 4b, 4d, 5c, 5d, 5g, 6b和 6d显示对PC12细胞缺氧损伤具有显著的保护作用,化合物4c, 5b和 6c显示对PC12细胞缺氧损伤具有一定的保护作用;在5μg/mL浓度下,4d和 6d显示对PC12细胞缺氧损伤具有一定的保护作用;初步的实验也表明：在10μg/mL浓度下,4c, 5a, 5c, 5d, 5e和 6b显示对PC12细胞具有一定的促分化作用。     

Synthesis,biological evaluation,and docking study of a series of 1,4-disubstituted 1,2,3-triazole derivatives with an indole-triazole-peptide conjugate

A series of new compounds containing an indole-triazole - peptide conjugate were designed as potential agents possessing the dual anti-bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi-step synthesis involving the copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, ¹H and ¹³C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram-positive (Staphylococcus aureus) and three gram-negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar-well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔG_bind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b , 9k, and 9e showed low IC₅₀ values.     

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.