氯硝柳胺衍生物的合成及抗肿瘤活性研究

以氯硝柳胺为起始原料,经醚化、亲核取代反应得到目标化合物,采用MTT法考察所合成化合物对人类乳腺癌细胞(MDA-MB-231)和人类胰腺癌细胞(ASPC-1)的体外抗肿瘤活性。合成了5个氯硝柳胺衍生物,其结构均经IR、1H-NMR、13C-NMR和MS确证。初步的体外抗肿瘤活性结果显示目标化合物9b和9c的抗肿瘤活性强于阳性对照药,其中化合物9b的活性对所测两种肿瘤株的抑制活性均强于阳性对照药,展现出较强的应用前景。     

新型萘酰亚胺衍生物的合成及抗肿瘤活性评价

本文合成了三种新的萘酰亚胺衍生物,并对其体外抗肿瘤活性进行了评价.初步实验结果表明,以芳基修饰氨萘菲特芳环上氨基所得化合物体外活性不如阳性对照氨萘菲特.而利用1,4-丁二醇修饰4-溴-1,8-萘酐芳环上溴原子得到的化合物3与阳性对照及其它两种衍生物相比对肝癌细胞HepG2具有较低的IC_(50)值.     

Synthesis and biological evaluation of novel acenaphthene derivatives as potential antitumor agents

Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by 1H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460), human colon adenocarcinoma (SW480), human breast cancer cell (MDA-MB-468 and SKRB-3), human melanoma cell (A375) and human pancreatic cancer (BxPC-3). Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.     

Synthesis and biological evaluation of novel indoleamide derivatives as antioxidative and antitumor agents

Novel indole amide derivatives C1-C10 were successfully synthesized and characterized by ¹H NMR, ¹³C NMR, IR, MS, and elemental analysis, and their molecular formulas were C₁₄H₁₀N₆O, C₁₃H₁₀N₄O, C₁₆H₁₃N₃O₂, C₁₉H₁₄N₂O₂, C₁₆H₁₁N₃OS, C₁₅H₁₃N₃O, C₁₂H₉N₅O, C₁₆H₁₀ClN₃OS, C₁₅H₁₇N₃O₂, and C₁₃H₁₄N₂O₃, respectively. The primary biological activities of these compounds were evaluated in vitro by the DPPH assay, H₂O₂-induced oxidative stress injury assay, and cytotoxicity assay. The results indicated that compounds C1, C2, C4, C7, and C9 exhibited DPPH·scavenging ability, while C3, C4, C5, and C8 showed potent growth-inhibitory activities against various human tumor cells, including MDA-MB-231, Hela, A549, and HT29. Interestingly, compound C4 showed potent scavenging effects on the DPPH radical and possessed protective effect on H₂O₂-induced oxidative stress injury in human neuroblastoma SH-SY5Y cells at low concentrations; however, C4 exhibited significant toxicity against four human tumor cells at a higher concentration in all treatments, and the range of IC₅₀ value was 7.91 to 13.35 μM.     

Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents

A series of pyrrolo[1,2-a]pyrazinone compounds(5a-9f) were synthesized,and their cytotoxic activity against SKOV-3,A549.HeLa cells in vitro were evaluated by the MTT method.Some of the compounds showed potential antitumor activity against three tumor cell lines.Among them,compounds 9c and 9d showed the most potent cytotoxic activity.The preliminary mechanism of action was discussed.     

Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents

To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the "combination principle" in drug discovery. The ligustrazine derivatives' anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD?? value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.     

Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol derivatives as potential antitumor agents

A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and evaluated on human cancer cell lines. Among them, compound 6p displayed potent and broad-spectrum anti-proliferative activities in vitro on some human cancer cell lines, even better than sorafenib. The advanced kinase inhibitory assays showed that compound 6p could selectively inhibit Aurora-B kinase. The biological results were rationalized by the molecular docking study, which indicated the stable interactions of 6p with the Aurora-B kinase.     

Synthesis and antitumor properties of new platinum(IV) complexes with aminonitroxyl radicals

Acylation of cis,trans,cis-Pt^IV(RNH₂)(NH₃)(OH)₂Cl₂ with acetic anhydride afforded complexes cis,trans,cis-Pt^IV(RNH₂)(NH₃)(OAc)₂Cl₂, where R is 2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl (1b) or 2,2,5,5-tetramethyl-1-oxylpyrrolidin-3-yl (2b). The complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectra. Complex 1b exhibits high antitumor activity comparable with that of Cisplatin against leukemia P388 used as the experimental tumor. Simultaneous administration of low doses of 1b and Cisplatin (1/20 of LD₅₀ each) results in synergism of the antitumor activity and 100% cure of animals. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 60–63, January, 2006.     

Synthesis and biological evaluation of new oxime-ether derivatives of steroid as anti-bacterial agents

Various oxime-ether derivatives of cholesterol have been synthesized by the alkylation of the steroidal oxime with 1-(2-chloroethyl) pyrrolidine hydrogen chloride/chloroethylamine hydrochloride in the presence of sodium methoxide in dry methanol. The structures of these compounds were elucidated by IR ¹H NMR, FAB mass spectroscopic methods and elemental analyses. The anti-bacterial activity was first tested in vitro by the disk diffusion method against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds were determined. The results showed that the chloro derivatives exhibited better anti-bacterial activity than the standard drug chloramphenicol.     

Synthesis and biological evaluation of picroside derivatives as hepatoprotective agents

Picrorhizae Rhizoma as a hepatoprotective herb, has been applied for thousands of years, and picroside was proved to be its active constituent. In this study, twelve derivatives of picroside were synthesized and the hepatoprotective activity of the derivatives was evaluated on SMMC-7721 cells. Six out of the derivatives had shown a better protective effect on H₂O₂-induced SMMC-7221 cells than picroside, and the activity of two derivatives (2 and 4) was stronger than that of the reference compound, silybin. Compound 2 shown the strongest protective effect (EC₅₀?=?6.064?±?1.295?μM).     

Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents

We have synthesized a series of compounds based on a piperidyl benzimidazole carboxamide structure,and tested their PARP-1 inhibitory activity,as well as cellular inhibitory activity.Some of them show great potency as PARP-1 inhibitors and antitumor activity,which are valuable for further research.In addition,the predicted ADME properties and proposed binding mode with PARP-1 of the compounds were obtained via computational simulation.     

Structural studies of diethyltin(IV) derivatives and their biological aspects as potential antitumor agents against Agrobacterium tumefacien cells

A series of new diethyltin(IV) derivatives of substituted phenyl acrylates have been synthesized and characterized by elemental analysis, IR, multinuclear NMR (¹H, ¹³C, ¹⁹F and ¹¹⁹Sn) and X‐ray single crystal analysis. X‐ray single crystal diffraction study of complex 8 has shown the formation of secondary O···Sn, F···H and H···O intermolecular interactions. These complexes proved to be good antitumor agents. The antitumor properties are presumably due to the intercalative mode of interaction of these complexes with the tumor cells' DNA. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro.Compound 10 and 16b,of which TI were>10,had some anti-HTV-l activity in vitro.Therein,compound 10 which was the best potent compound,could serve as a new lead for further development of anti-AIDS agents.     

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro.The results showed that compounds 6A and 6B exhibited good antifungal activity.Compound 6A8 showed the strongest antifungal activity,which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole.In particular,the antifungal activity of compound 6A8 against Candida albicans and Candida krusei(MIC80 both at 0.00097μg/mL) was 515 and 64 times that of Fluconazole,respectively.The structure-activity relationships of the synthesized compounds were discussed,and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.     

Synthesis and biological evaluation of n-butylphthalide derivatives as anti-platelet aggregation agents

New analogues of n-butylphthalide (NBP) bearing various lengths of alkyl and different substitution at the two-position of phthalide were designed and synthesised. Preliminary evaluation and prediction of ACD LogP software indicate that the derivatives display significant improvement in water solubility than NBP does. Further biological analysis showed that NBP analogues specifically inhibit platelet aggregation induced by arachidonic acid but have no effect on that induced by adenosine 5-diphosphate. Especially compounds 1 and 3 were stronger than classical anti-platelet drug, aspirin, and equal potent with NBP, respectively. These findings provide an alternative approach to the development of NBP analogues with anti-platelet aggregation activity with good water solubility for the intervention of ischemic stroke.     

Synthesis and biological evaluation of dihydrotriazine derivatives as potential antibacterial agents

A series of 1,4-dihydro-1,3,5-triazine derivatives were designed and synthesized and their antibacterial and antifungal activities were evaluated. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains(including multidrug-resistant clinical isolates) and Gramnegative bacterial strains, with minimum inhibitory concentrations(MICs) in the range of 2.1–181.2 mmol/L. Compounds 7a and 7c presented the most potent inhibitory activities against Grampositive bacteria(e.g., Staphylococcus aureus 4220), Gram-negative bacteria(e.g., Escherichia coli 1924),and the fungus Candida albicans 7535, with MICs of 2.1 or 4.1 mmol/L. Especially, compound 7a was the most potent, with an MIC of 2.1 mmol/L against four multidrug-resistant, Gram-positive bacterial strains.The cytotoxic activity of the compound 7a, 7c and 7f was assessed in HepG2 cells, and the results suggest that 1,4-dihydro-1,3,5-triazine derivatives bearing a 6-benzyloxynaphthalen moiety are interesting scaffolds for the development of novel antibacterial agents.     

DNA binding and antitumor activities of platinum(IV) and zinc(II) complexes with some S-alkyl derivatives of thiosalicylic acid

A series of complexes of platinum(IV) (C1–C5) and zinc(II) (C6–C10) with S-alkyl derivatives of thiosalicylic acid were prepared and characterized. The interactions of the complexes with calf thymus DNA were analyzed by absorption (UV–Vis) and emission spectral studies (ethidium bromide displacement studies). The cytotoxic activities of complexes C1–C10 were determined against mouse B cell lymphocytic leukemia cells (BCL1), human B-prolymphocytic leukemia (JVM-13), mouse mammary carcinoma cells (4T1), and human mammary carcinoma cells (MDA-MB-468) and compared to the activities of the free ligand precursors and cisplatin. The cytotoxicities of the platinum(IV) and zinc(II) complexes toward mouse tumor cell lines were higher compared with their effects on human tumor cell lines. The zinc(II) complex C9 showed the highest antitumor activity toward the tested human cell lines, while the platinum(IV) complex C4 exhibited the highest antitumor activity toward mouse BCL1 and 4T1 cells. Both C4 and C9 have ligands derived from S-propyl thiosalicylic acid.     

Synthesis and biological evaluation of new 3-trifluoromethylpyrazolesulfonyl-urea and thiourea derivatives as antidiabetic and antimicrobial agents

Fluorinated pyrazoles, and benzenesulfonylurea and thiourea derivatives as well as their cyclic sulfonylthioureas 2-18 were prepared as hypoglycemic and antibacterial agents. The chemistry involves the condensation of 4-hydrazino benzenesulfonamide hydrochloride with 1-trifluoromethyl diketones 1 to give pyrazole derivatives 2 which upon bromination gave the bromopyrazole 3. Reaction of 2 or 3 with isocyanates and isothiocyanates gave the corresponding ureas 4 and 5 and thioureas 6 and 7. Cyclization of thiourea derivatives with ethyl bromoacetate, ethyl β-bromopropionate, 1,3-dichloroacetone and α-bromoacetophenone yielded the corresponding 4-oxothiazolidines 8 and 9, 4-oxo-5,6-dihydrothiazine 10, 5-oxo-4,5-dihydrothiazines 11 and 12 and thiazolines 13 and 14. Preliminary biological screening of the prepared compounds revealed significant antidiabetic and antibacterial activities.     

Synthesis and biological evaluation of some novel thiadiazole-benzofuran hybrids as potential antitumor agents

Two series of novel 1,3,4-thiadiazole-benzofuran and 1,3,4-thiadiazole-furochromene derivatives were synthesized through heterocyclization of alkyl 2-(1-(6-hydroxy-4,7-dimethoxybenzofuran-5-yl)ethylidene)hydrazine-1-carbodithioate 3a–f and 2-(1-(5-methoxy-8-methyl-2,6-dioxo-2,6-dihydropyrano[3,2-g]chromen-3-yl)ethylidene)hydrazinecarbothioamide 9a,b with various hydrazonoyl halides, respectively. The structure of the newly synthesized products was elucidated through elemental analysis, spectral data and alternative routes whenever possible. Ten new compounds were evaluated for their anticancer activity against the human breast carcinoma (MCF-7) cell lines in comparison with reference doxorubicin using MTT assay. The results showed that some new compounds have promising anticancer activity.     

Synthesis of 3'-beta-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents

3'-beta-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI2 as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure-activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5'-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.