某些B-降胆甾噻唑化合物的合成及抗肿瘤活性研究

从胆甾醇出发,合成了系列B-降胆甾烷噻唑化合物,通过IR、NMR及HRMS等现代分析方法对合成物进行了结构表征.同时,分别采用人肺癌细胞(A549)、宫颈癌细胞(He La)、肝癌细胞(HEPG2)和人正常肾上皮细胞(HEK293T)对合成产物进行体外抑制肿瘤细胞增殖活性研究,结果表明具有N-甲基噻唑结构的化合物14和17对A549和HEPG2细胞的生长增殖表现出较好的抑制活性;具有N-苯基噻唑结构的化合物20~24对He La细胞表现出选择性的增殖抑制作用,但对人正常肾上皮细胞却几乎没有作用.     

吖啶-多胺类缀合物的合成、 抗肿瘤活性及与DNA键合作用

设计合成了系列吖啶-多胺类衍生物(ACP1~ACP6), 并通过四甲基偶氮唑蓝(MTT)染色法研究了化合物对K562(人白血病细胞)、 A549(人肺癌细胞)和Hela(人宫颈癌细胞)细胞株的体外抗肿瘤活性. 结果显示, 化合物对肿瘤细胞具有一定的抑制作用, 尤其是化合物ACP2的抗肿瘤活性优于阳性对照顺铂. 通过UV-Vis光谱、 荧光光谱、 圆二色谱和热变性实验研究了合成化合物与小牛胸腺DNA(Ct-DNA)的键合作用. 结果表明, 三乙烯四胺修饰的化合物ACP2具有较好的抗肿瘤活性, 与DNA分子具有较强的结合能力.     

N-乙酰基吡唑啉衍生物和二苯醚基N-乙酰基双吡唑啉衍生物的合成及体外抗肿瘤活性

合成了7个N-乙酰基吡唑啉化合物2a~2g和7个新型的二苯醚基N-乙酰基双吡唑啉化合物4a~4g,通过核磁共振谱、元素分析和质谱对合成化合物进行了结构表征.并且用3-(4,5-二甲基吡啶-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺苯基)-2H-四唑(MTS)法测试了它们对人肺腺癌细胞(A549)、人非小细胞肺癌细胞(H1299)和乳癌细胞(MCF-7)三类癌细胞株的体外抗肿瘤活性.结果显示,所合成的化合物对癌细胞有一定抑制作用,其中3,3'-(4,4'-二苯醚基)双[1-乙酰基-5-(3,4-亚甲基二氧苯基)-2-吡唑啉](4e)对A549,H1299和MCF-7三类癌细胞株具有较好的抗肿瘤活性,半数抑制浓度(IC50)分别为16.91,10.09,10.97μmol/L.     

芹菜素衍生物的合成及抗肿瘤活性研究

以芹菜素为起始原料,在C-5、C-6、C-7、C-4′位置上引入甲基、苄基、乙酰基、对甲苯磺酰基、三异丙基硅烷基等多种单元结构基团,合成了16个芹菜素衍生物,采用CCK-8的方法考察了所合成化合物对人肝癌细胞(Hep3β)、人结肠癌细胞(LOVO)、人肺癌细胞(A549)的抑制作用。结果显示,经过化学修饰后的部分化合物比芹菜素有更强的抗肿瘤活性,其中化合物13对人肺癌细胞(A549)的抑制率超过了顺铂,值得进一步探讨和研究。     

新型查尔酮衍生物的合成及抗肿瘤活性评价（英文）

主要通过Claisen-Schmidt缩合反应设计合成了一系列含有哌啶、吗啡啉、N-甲基哌嗪取代的查尔酮衍生物,并通过噻唑蓝(MTT)法对MCF-7(人乳腺癌细胞系)、A549(人肺癌细胞系)、HL-60(人白血病细胞系)、Hela(人宫颈癌细胞系)和Bewo(人绒毛肿瘤细胞系)等五种癌细胞系进行了体外抗癌活性研究.研究表明,化合物4a,4e,4f,4j,4m,4o对MCF-7, A549, HL-60三种癌细胞系抗癌活性最佳, IC_(50)值均在10μmol/L以下.     

新型含三氟甲取代喹啉衍生物的合成及其抗肿瘤活性

为了寻找高效低毒的抗肿瘤活性化合物,设计并合成21个新型含三氟甲基取代喹啉酰胺类衍生物,其结构经~1H NMR、~(13)C NMR及~(19)F NMR和MS(ESI)进行了确证。用MTT法评价了所得目标化合物对乳腺癌细胞(MDA-231)、前列腺癌细胞(LNCAP)、人肺癌细胞(A549)、肾癌细胞(A498)和宫颈癌细胞(Hela)增殖的抑制活性。     

C-13位烷氧基赤霉素衍生物的合成与抗肿瘤活性研究

设计并合成了系列C-13位为醚结构且在A环和D环有两个α,β-不饱和酮结构的赤霉素衍生物.采用噻唑蓝(MTT)法评价了其对人肺腺癌细胞(A549)、人肝癌细胞(HepG2)、人胃癌细胞(MKN28)以及结肠癌细胞(HT29)的体外生长抑制作用,结果表明:此类化合物都有较强的体外抗肿瘤活性,其中化合物27的活性最强(对人胃癌细胞MKN28的IC50=0.21μmol·L-1),优于阳性对照药物顺铂(DDP).     

新型5,6-二氢-6-烷基吡喃酮类衍生物的设计、合成及肿瘤细胞增殖抑制活性研究

为了研究吡喃酮结构中不饱和双键修饰对该类化合物生物活性的影响.基于5,6-二氢-6-烷基吡喃酮类化合物哥纳香甲素,通过不饱和双键的修饰,设计合成了化合物5,6和8.利用噻唑蓝(MTT)法评价了目标化合物对人肝癌细胞(7721)、人肺癌细胞(A549)、人食管癌细胞(EC-109)、人胃癌细胞(MGC-803)的细胞增殖抑制活性.通过和阳性药物的对比发现,除了4-(2,3,4,5-四氟)苯甲酰氨基-3-甲基-6-苄氧甲基-5,6-二氢-吡喃-2-酮(6d),所合成化合物的肿瘤细胞增殖抑制活性均消失.结果表明,在5,6-二氢-6-烷基吡喃酮类化合物结构中,不饱和双键起着至关重要的作用,对其进行适当的修饰,在保留其活性的同时,具有潜在改善其因共价键结合引起毒性的可能性.     

(20R)-孕甾-5-烯-20-(2-甲氧基苯甲酸酯)类化合物的合成及抗肿瘤活性

从孕烯醇酮出发,通过酯化反应在3-位羟基上引入不同结构酯链,再对20-位羰基进行结构修饰,合成了10个(20R)-孕甾-5-烯-20-(2-甲氧基苯甲酸酯)类化合物,并通过IR、NMR及HRMS方法进行了结构表征。合成的化合物用噻吩蓝比色法(MTT)体外测试了对人宫颈癌细胞(HeLa)、人肺癌细胞(A549)、人甲状腺癌细胞(TPC-1)、人鼻炎癌细胞(CNE-2)以及人正常肾上皮细胞(HEK-293T)的增殖生长抑制活性,结果显示化合物2d和3d对A549的抑制效果显著,其IC₅₀达到了7.9 μM和10.3 μM,而对人正常肾上皮细胞 HEK-293T细胞无毒性。     

4-(5H-嘧啶并[5,4-b]吲哚-2-基-氨基)苯甲酰胺类化合物的设计、合成及抗肿瘤活性研究

设计、合成了19个未见文献报道的4-(5H-嘧啶并[5,4-b]吲哚-2-基-氨基)苯甲酰胺类衍生物,所有化合物结构均经~1H NMR、~(13)C NMR及HRMS确认。采用噻唑蓝(MTT)法测试了目标化合物对人结肠癌细胞(HCT116)、人乳腺癌细胞(MD-MBA-231)、大鼠神经胶质瘤细胞(C6)、人非小细胞肺癌细胞(A549)、人乳腺癌细胞(MCF-7)的体外抗肿瘤活性。所有化合物均表现出较好的抗肿瘤活性,其中5a、5b、5c、5e、5i、5p和5r对多个细胞株的抑制活性为阳性对照药品5-氟尿嘧啶的20～100倍;其中,以5b的抗肿瘤活性最为突出,对肿瘤细胞HCT116、MD-MBA-231、C6、A549、MCF-7的IC_(50)分别为3. 26、3. 06、0. 63、0. 68、2. 32μmol/L。初步研究结果表明,此类化合物对肿瘤细胞增殖有明显抑制作用,为新型抗肿瘤化合物的设计、合成提供了思路。     

Design,Synthesis, and Anticancer Activity of 3H–benzo[f]chromen‐3‐one Derivatives

A series of substituted aminomethylbenzocoumarin derivatives 8a–i have been synthesized, characterized, and structure of compound 8g was confirmed by X‐ray single crystal analysis. All the synthesized compounds were tested for their anticancer activity against cancer cell lines A549 (lung carcinoma cell line), MCF7 (breast cancer cell line), and A375 (melanoma cell line). Compounds 8a , 8f , and 8h showed excellent growth inhibitory activity against all three cell lines, respectively. Compounds 8a and 8f were also found to be quite promising at very low concentration as an anticancer agent against MCF7 and A549 cell lines. Compounds 8g and 8i showed excellent antimitotic activity with IC₅₀ 0.32 and19.98 nM for A549 cell line.     

Applying Cu(II) complexes assisted by water-soluble porphyrin to DNA binding and selective anticancer activities

Cancer is one of the killers endangering human health and its treatment has always been a focus of the medical community. For anticancer drugs, water-soluble porphyrin and Schiff bases have always been of interest. We report here three Cu(II)-based complexes functionalized by water-soluble cationic porphyrin and hydrazine Schiff base, which were prepared and evaluated for their biological activity. The three Cu(II) complexes all exhibited potent binding affinity to calf thymus DNA, the strongest interaction being between CuP2 and DNA. We studied the cytotoxicity of the complexes and ligands against different types of cancer cells (A549, H-1975, HepG2 and T47D), results showing the ligands are less cytotoxic; therefore, the anticancer activity of the complexes is improved by complexation. Furthermore, the cytotoxicity of ligands and complexes was also evaluated against the normal cell line Hs 578Bst, complexes showing more negligible cytotoxicity than ligand. Moreover, the cellular uptake of these Cu(II) complexes was investigated using the extraction method and results suggested that CuP2 exhibits the best cellular uptake towards H-1975 cells. Interestingly, fluorescence microscopy experiments and flow cytometric analysis (cell cycle) were used to further investigate the potent anticancer activities.     

Synthesis,anticancer and antimicrobial evaluation of new pyridyl and thiazolyl clubbed hydrazone scaffolds

Abstract

A series of new hydrazones bearing pyridyl and thiazolyl scaffolds have been synthesized and evaluated for their in vitro anticancer and antimicrobial activities. The anticancer activity was evaluated against the A549 lung cancer cell line. The eight hydrazone derivatives have shown better anticancer activity than positive control doxorubicin against the A549 lung cancer cell line. The antimicrobial activity was evaluated against bacterial and fungal pathogens by using well diffusion method. The four hydrazone derivatives have displayed good antimicrobial activities. Molecular docking studies of the synthesized hydrazone derivatives revealed good binding via hydrogen bond interactions with key residues on active sites as well as neighboring residues with an active site of Focal adhesion kinase (PDB ID 2JKO). A computational study for the prediction of absorption, distribution, metabolism, and excretion (ADME) properties of all compounds has also been performed.     

Bioactive Fluorenes. Part II. Unprecedented biologically active thiazole derivatives based-2,7-dichlorofluorene as competent DHFR inhibitors: Design,synthesis, and molecular docking approaches

In this study, a new series of (4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-yl)acetamide derivatives was synthesized, and the new heterocycles were completely characterized, evaluated for their antimicrobial activity, and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was undertaken to identify the possible mode of action of the synthesized compounds, which suggested binding interactions with the dihydrofolate reductase (DHFR) active sites.Most of the synthesized compounds displayed meaningful activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. Furthermore, some of the prepared compounds exhibited potent antibacterial and antifungal activities. The highly pronounced biological activities of the compounds under investigation offer such species as promising future drug prospects which may find applications in the fields of biological and medicinal sciences.     

One‐Pot Synthesis of New Thiadiazolyl‐Pyridines as Anticancer and Antioxidant Agents

The reaction of one equivalents of 5‐acetylthiadiazole with one equivalent of aldehyde in acetic acid and ammonium acetate yielded thiadiazolyl‐pyridine derivatives in a multicomponent reactions. The structures of all the new compounds were elucidated on the basis of elemental analysis and spectral data. The anticancer activities of the synthesized compounds were screened for their activity against human lung carcinoma (A549) and human hepatocellular carcinoma cell lines (HepG2) comparable with cisplatin, and the results showed that most of such compounds exhibit considerable activities. The order of activity against A549 cell line was 4c , 4e , 4a , 6d , 8d , 11 , 12 , 4b , 4f , and 4d . However, compound 4e exhibited the highest activity against HepG2, followed by 4a , 4c , 6d , 8d , 11 , 12 , 4f , 4d , and 4b . On the other hand, compounds 11 , 12 , and 4b showed the highest 2,2‐diphenyl‐1‐picrylhydrazyl free radical scavenging activities. Conclusively, the results of the current study approved the cytotoxic and antioxidant capabilities of the synthesized compounds.     

Synthesis,characterization, cytotoxicity and computational studies of new phosphine‐ and carbodithioate‐based palladium(II) complexes

In quest of new metallo‐pharmaceuticals with enhanced anticancer activity, four new phosphine‐ and carbodithioate‐based Pd(II) complexes of the type [(R)CS₂Pd(PR₃)Cl] (where R = 4‐(2‐hydroxyethyl)piperazine ( 1 , 2 ), dibenzyl ( 3 , 4 ); PR₃ = diphenyl(p ‐tolyl)phosphine ( 1 , 3 ), tris(4‐tolyl)phosphine ( 2 , 4 )) were synthesized and characterized using elemental analysis, Fourier transform infrared and NMR (¹H, ¹³C and ³¹P) spectroscopies and single‐crystal X‐ray diffraction. The X‐ray diffraction data confirmed the pseudo square‐planar geometry ensuring bidentate coordination mode of carbodithioate ligands. Anticancer activity of the synthesized complexes and their ligands was assessed against human lung (A549), breast (MCF‐7) and prostate (PC3) carcinoma cells using MTT assay. All the tested compounds showed activity in micromolar range. In many cases, the cytotoxicity of the synthesized complexes was higher than or comparable to that of the standard drugs cisplatin and doxorubicin. Complex 3 emerged as the most promising compound with the lowest IC₅₀ values of 4.83, 3.72 and 5.11 μM for A549, MCF‐7 and PC3 carcinoma cell lines, respectively. DNA binding studies were also carried out using UV–visible spectroscopy. We extended our investigations to explore the mechanism of anticancer activity using in silico tools. Based on the mechanism of action of standard drugs used, extensive docking studies were carried out on the three different biomolecular targets.     

Design,Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methylbiphenyl Moiety

A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety, which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-75 A549, H460 and HT29) and PD-1/PD-L1 inhibitory activities. Moreover, several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293). The most promising compound llo showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45, 8.65, 6,57 and 8.13 gmol/L, respectively, and displayed weak cytotoxicity on the normal cell(HEK-293). Furthermore, screening of PD-1 /PD-L1 inhibitory activity revealed that compound llo could effectively inhibit the binding of PD-1/PD-L1, and the binding interactions of compound llo with PD-L1 protein were explored by molecular docking. All above evidences showed that compound llo might be worthy of further study as a valuable leading compound for the treatment of cancer.     

Design,synthesis, and biological evaluation of sorafenib derivatives containing indole (ketone) semicarbazide analogs as antitumor agents

A series of new sorafenib derivatives was designed and synthesized. The antiproliferative activity of the synthesized compounds against human lung cancer cell (A549), human pancreatic cancer cell (PC-3), human leukemia cell (K562), and human hepatoma cell (SMMC-7721) was evaluated by MTT assay. The results revealed that several compounds displayed more significant antitumor activities than commercial anticancer agent sorafenib against SMMC-7721. In addition, compounds 7a , 7g , 7l , 7m , and 7p represented obvious growth inhibition with IC₅₀ values of 1-9 μM against four cancer cell lines, demonstrating more predominant activities against cancer cells as compared to sorafenib. Furthermore, some structure-activity relationships have also been established. Compounds containing indole and benzene ring substituted by halogen showed better activity than sorafenib. Wound healing assay suggested that cells would be targeted on their migratory capacity by 7g , potentially affecting the migration activity of these tumors. The effects of A549 and PC-3 cell apoptosis induced by compound 7g were significantly increased compared with sorafenib. Importantly, the result of western blot assay showed that 7g inhibited cell growth by suppressing the activity of EGFR, especially the expression of p-EGFR (Tyr1068).     

Synthesis,crystal structure,DNA interaction and anticancer evaluation of pyruvic acid derived hydrazone and its transition metal complexes

A novel tridentate chelating ligand, Ethyl 2‐(2‐(2‐chlorobenzoyl)hydrazono)propanoate and its late transition metal complexes were synthesized, characterized and evaluated for anticancer behavior. The structures were elucidated with the help of elemental analyses, spectral (vibrational, electronic, NMR and mass) and thermo‐gravimetric techniques. Single crystal X‐ray crystallographic studies of the ligand suggest an orthorhombic lattice structure with Pna21 space group. The interaction of ligand and complexes with DNA (CT‐DNA) has been extensively studied using absorption, emission, viscosity and thermal denaturation studies with E. coli DNA. The DNA cleavage ability of ligand and metal complexes was tested using plasmid pBR322 DNA by gel electrophoresis method. The ligand and its copper complex have been evaluated for their in vitro anticancer activity against human cancer cells of different origin such as KB (Oral), A431 (Skin), Mia‐Pa‐Ca (Pancreases), K‐549 (Lung), K‐562 (Leukemia), MCF‐7 (Breast) and VERO by MTT assay and the apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining method. The studies suggest that ligand and copper complex exhibit significant cytotoxic activity on KB, MCF‐7, A‐431, Mia‐Pa‐Ca‐2 an d A‐549 cell lines compared to K‐562 and VERO cell lines.