Synthesis and antitumor activity of derivatives of 23-hydroxybetulinic acid

A series of natural product 23-hydroxybetulinic acid derivatives were prepared.In the preparation of mono-O-benzoyl ester derivative,it was observed that benzoyl group migrated from 3-O-to 23-O-position during the detritylation.     

Synthesis and in vitro antitumor activity of novel naphthyridinone derivatives

A series of naphthyridinone derivatives based on la(a precursor of Voreloxin) were designed and synthesized.Seven compounds having 70%inhibition against HL60 at 30 μmol/L were further evaluated for their in vitro antitumor activity by SRB assay.Results reveal that thiazol-2-yl and 3-aminomethyl-4-benzyloxyimino-3-methylpyrrolidin-l-yl groups are optimal at the N-1 and C-7positions of naphthyridinone core,respectively.10 j exhibits broad-spectrum activity(IC_(50):0.5-6.25 μmol/L) against all of the tested cell lines including Etoposide- and/or la-resistant ones,and is 1.3-fold to 100-fold more potent than the two references against eight of these cell lines.     

Synthesis and in vitro antitumor activity of novel diaryl urea derivatives

A series of novel diaryl ureas containing 4-[（2-amino-6-trifluromethyl）pyrimidine-4-yl]piperazine-l-yl group were synthesized and evaluated for their cytotoxic activities in a panel of human cancer cell lines. Compared with the reference drug Sorafenib,some compounds showed more potent and a broader spectrum of anti-cancer activities.Among them,compound 2p demonstrated significant inhibitory activities against MDA-MB-231,HT-29 and MCF-7 cell lines with IC₅₀ values of 0.016,0.63,0.001μmol/L, respectively.     

Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method. The results showed that some of the compound had higher antitumor activity than iritecan.     

Synthesis and antitumor activity of 7-azaindirubin

Twenty 7-azaindirubin derivatives were designed and synthesized.Their antitumor activities were evaluated in vitro against DU145 cell line.The pharmacological results showed that most of the prepared compounds displayed the excellent activity.Compound 18 exhibited the most potent antitumor activity among the tested compounds.     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

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.     

Synthesis and antitumor activity of nitric oxide releasing derivatives of AT1 antagonist

A series of novel nitric oxide-donating derivatives(7a-e,8a-e) were synthesized by coupling furoxan and nitric oxide with irbesartan analogue and their cytotoxicity against BEL7402 cells in vitro were evaluated by MTT method.It was found that 8c exhibits the most cytotoxic activities with ICso value of 12.5μmol/L.The hybrids of AT 1 antagonist and nitric oxide donor appear to have beneficial effects on antitumor.     

Synthesis and cytotoxic activity of 7-alkynyl camptothecin derivatives

Several 7-alkynyl camptothecin derivatives were prepared via Sonogashira coupling.And anti-tumor activities of these compounds were evaluated against human esophageal cancer cell line (Eca-109),human chronic myeloid leukaemia cell line (K562),bladder cancer cell line (5637) and gastric cell line (SGC7901).Compounds 9a-d and 10a exhibited remarkable in vitro cytotoxic activity,compared with topotecan.     

Synthesis and antitumor activity of 9-methyl-10-hydroxycamptothecin

A novel camptothecin analogue, 9-methyl-10-hydroxycamptothecin （4）, was unexpectedly synthesized from 10-hydroxycamptothecin in two steps. The key step included an efficient Mannich-type reaction. The overall yield was 47.2%. An ether analogue of 4, 9-methyl-10-benzylaminomethoxycamptothecin （5）, was also prepared. These new camptothecin analogues were evaluated for in vitro cytotoxicity against four human cancer cell lines, and exhibited more potent antitumor activities than contrals camptothecin and topotecan against several cancer cells.     

Synthesis and antitumor activities of structure-related small molecular compounds of gambogic acid

Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure-activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.     

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole, a famous anthranilic diamide insecticide targeting the insect ryanodine receptor (RyR), have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials. With the aim of discovering new heterocyclic pesticides used for crop protection, based on the structural information of compound M from the reported pharmacophore-based virtual screening for RyR insecticides and diamide compound, a series of new heterocyclic mono-, di-, and tri-amide derivatives containing piperazine moiety have been synthesized in this paper. The new compounds were identified and confirmed by melting point, ¹H NMR, ¹³C NMR and HRMS. Compound M was firstly validated for insecticidal activities, and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm. The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials, particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8g, 14a, 15a, 15g, 15i, 15j, 15k, 15l, and 15m could be used as new insecticidal leading structures for further study (e.g., towards diamondback moth, 15i-15m LC₅₀: 0.0022−0.0081 mg/L). The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.     

Design,synthesis and antitumor activity of 3-substituted quinolone derivatives （Ⅰ）

A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor ceils are comparable to that of topotecan, one of topoisomerase I inhibitors.     

Synthesis and antitumor activity of novel podophyllotoxin derivatives

In order to find compounds with superior bioactivity and overcoming multidrug resistance,a novel series of 4β-N-substituted podophyllotoxin derivatives were synthesized and evaluated as potential antitumor agents.Seven novel podophyllotoxin derivatives were synthesized by linking-4β-amino-4-deoxypodophyllotoxin with alcohols through maleic acid and tested against K562 and K562/A02 using MTT assay in vitro.     

Facile synthesis and cytotoxicity of 5-C-alkylates of 20（S）- camptothecins

A series of 5-C-alkylating camptothecins have been synthesized by one-step method, and their in vitro antitumor activity was evaluated against six human cancer cell lines. The results showed that all 5-C-alkylates of camptothecins possessed poor cytotoxicity on six human cancer cell lines.     

Synthesis and antitumour activity of arctigenin amino acid ester derivatives against H22 hepatocellular carcinoma

Arctigenin (ARG) is famous in its abundant pharmacological activity. However, many researches in it entered the bottleneck period because of its poor water solubility. The derivatives of ARG have been synthesised with five amino acids which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the effects of removing BOC. The results showed that the amino acid derivatives without protective group have better water solubility and nitrite-clearing ability than ARG. Based on these results, ARG6′ and ARG9′ were selected at a dosage of 40 mg/kg to evaluate their antitumour activity. The percentage inhibition rate of ARG6′ and ARG9′ were 55.87 and 51.40, respectively, which was twice as much as ARG. Furthermore, they could increase liver and kidney indexes and produce less damage in these organs. In brief, this study provides a basis for new drug development.     

Synthesis and antitumor activity of α-aminophosphonate derivatives containing thieno[2,3-d]pyrimidines

Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive a-aminophosphonate subunits were introduced at the N3 position through an N–N bond connection.The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells(EC109), human hepatocarcinoma cells(Hep G2), human gastric carcinoma cells(MGC-803),respectively, by the MTT method. The evaluation results revealed that compounds 6mb, 6mf, 6mg, 6nd and 6nh exerted the most potent inhibition against Hep G2, MGC-803 and EC109 cells, respectively. In particular, compound 6mg presented excellent inhibitory effect against Hep G2(91.2%) and MGC-803(94.4%) cells.     

Design, synthesis and antitumor activity of 6,7-disubstituted-4-(heteroarylamino)quinoline-3-carbonitrile derivatives

<正>A series of new 6,7-disubstituted-4-(benzothiazol-6-ylamino)quinoline-3-carbonitrile derivatives(12a-l) were synthesized.The cytotoxicity of 12 new compounds was evaluated in AGS,HepG2 and HT-29 cell lines.The results showed that compounds 12g, 12h,12i,12k and 12l displayed more potent cytotoxic activities than Bosutinib,compound 12l exhibited the most potent antitumor activity among the tested compounds.     

20(S)-20-O-Camptothecin β-Aminopropionate: Novel Synthesis and Antitumor Activity in vitro

To improve the biological anticancer activity of 20(S)-camptothecin, a novel class of 20(S)-20-O-camptothecin β-aminopropionates were designed and synthesized with camptothecins as the starting materials, through acylation with acryloyl chloride followed by Michael′s addition. Twelve esters, 1a-1d, 4a-4d and 5a-5d, were synthesized and evaluated by using MTT assay method. The results demonstrate that all these compounds show a potential cytotoxicity on KB, HT-29, HCT-8, and Bel7402 tumor cell lines. Some compounds, 1d, 4c, 5b, 5c and 5d, show a higher cytoto-xicity on KB and HCT-8 compared with camptothecin.     

积雪草酸衍生物的合成及抗肿瘤活性研究

以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基、C-11位氢、C-28位羧基进行结构改造,合成了13个新的积雪草酸衍生物,其结构经MS及1H NMR等确证。采用MTT法,选用高表达人癌细胞(He La、Hep G2和BGC-823)对它们进行初步的体外抗肿瘤活性研究,结果表明,所测化合物对He La、Hep G2和BGC-823肿瘤细胞的抑制活性均明显强于积雪草酸,其中化合物I4和II4对He La、Hep G2和BGC-823细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究。