Synthesis and in vitro biological evaluation of farnesylthiosalicylic acid derivatives as anti-tumor carcinoma agents

Novel farnesylthiosahcylic acid(FTA) derivatives 5a-m with different substituted 1,3,4-thiadiazoles were synthesized. Compounds 5b,5c,5e and 5f displayed anti-tumor activities superior to FTA in most cancer cells tested.Furthermore,5e induced tumor cell apoptosis,which was accompanied by lower Bcl-2 expression,but with higher Bax and caspase 3 expression activities in cancer cells.     

Synthesis and in vitro biological evaluation of novel 2-aminoimidazolone derivatives as anti-tumor agents

Novel 2-aminoimidazolone derivatives were synthesized.Most compounds displayed strong anticancer activities against human carcinoma cells in vitro.Compounds 8a,8b and 8j exhibited optimal activity superior to 5-FU in most cancer cells tested.Especially,the lC₅₀s of 8b（12.6-21.5μmol/L） against five tumor cells were 1 -4 fold less than those of 5-FU（18.4-56.1μmol/L） in vitro.Furthermore,comp以ound 8b could induce SMMC-7721 cell apoptosis in a dose-dependent manner.Therefore,our novel findings may provide a new framework for the design of new 2-aminoimidazolone derivatives for the treatment of cancer.     

Synthesis and in vitro biological evaluation of nitric oxide-releasing derivatives of hydroxylcinnamic acids as anti-tumor agents

Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines. Compounds 6a, e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil (5-FU) in most cancer cells tested. Furthermore, 6f could selectively inhibit tumor cells, but not non-tumor cell proliferation. This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids.     

Synthesis and biological evaluation of novel furozan-based nitric oxide-releasing derivatives of oridonin as potential anti-tumor agents

To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9 h exhibited the most potential anti-tumor activity with IC?? values of 1.82 μM against K562, 1.81 μM against MGC-803 and 0.86 μM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.     

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).     

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。     

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.     

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 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 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 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 theophylline acetohydrazide hydrazone derivatives as antituberculosis agents

A series of small molecules, theophylline acetohydrazide hydrazone derivatives were obtained via condensation of theophylline-7-acetohydrazide with different aromatic/heterocyclic aldehydes. The compounds were synthesized and characterized by using conventional methods. Further, the compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain, the activity obtained was varying depending on the functional group attached to theophylline acetohydrazide hydrazone compounds. Among these, Br-substituted compounds showed more potent against M. tuberculosis with MIC 3.6–4 μM and better than the reference drugs used. The molecular docking studies have shown the possible binding modes of the compounds with protein (PDB ID: 4RHX); the compound 4h has shown highest glide score and binding energy. For all compounds, ADME properties were predicted.     

Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents

A novel series of indole-3-carboxamide derivatives (6a-6l) have been designed, synthesized and evaluated for their antioxidant activity against human neuroblastoma SH-SY5Y cell line using H2O₂ radical scavenging assay. Biological activity evaluation showed that compounds 6a, 6f and 6i exhibited significant in vitro activities, which could have the potential to be developed for novel antioxidants.     

Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents

Oxidative stress results in various pathologies and as consequence antioxidant agents have attracted uninterrupted attention. In this paper, a novel series of indole-3-carboxamide derivatives (6a–6l) were designed and synthesized based on the melatonin structure as novel antioxidants. All of them were evaluated for the antioxidant activities in vitro against human neuroblastoma SH-SY5Y cell line using H₂O₂ radical scavenging assay. The target compounds 6a, 6f and 6i indicated better activities than the positive control, ascorbic acid, and 6a exhibited the best antioxidant activity. In addition, the structure-activity relationships of the target compounds were also preliminarily summarized based on the obtained experimental data.     

Synthesis and biological evaluation of nitric oxide-releasing matrine derivatives as anticancer agents

<正>A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil against human hepatoma cells(HepG2) in vitro.