Synthesis and antiproliferative activity of new 1,2,3-triazole/flavone hybrid heterocycles against human cancer cell lines

Russian Journal of General Chemistry - A series of new 1,2,3-triazole/flavone hybrid heterocycles were synthesized from 6-amino flavone via key intermediate N-propargyl flavone 6 by adopting the...     

Artemisinin-isatin hybrids with potential antiproliferative activity against breast cancer

Three series of artemisinin-isatin hybrids 8a-i, 10a-c and 11a-e were designed, synthesized and evaluated for their antiproliferative activity against breast cancer cells (MCF-7, MDA-MB-231 and doxorubicin-resistant MCF-7 (MCF-7/DOX)), as well as the cytotoxicity towards normal MCF-10A breast cells. The preliminary results showed that a significant part of the synthesized hybrids (IC₅₀: 20.7–99.9 µM) were active against both drug-sensitive and doxorubicin-resistant breast cancer cell lines. The structure–activity relationship illustrated that the linker between artemisinin and isatin moieties as well as the substituents on C-3 and C-5 position of isatin motif had great influence on the activity. In particular, hybrids 11c,d were found to be most active against all tested breast cancer cell lines, and their activity was not inferior to that of doxorubicin. Therefore, hybrids 11c,d could serve as useful templates for the development of novel anti-breast cancer agents.     

Phosphine-catalyzed acyl-transfer of heteroaryl ketones for the construction of N-fused heterocycles

An inexpensive phosphine catalyst was used effectively for a transition-metal-free acyl-transfer of N-containing heteroaryl ketones for the rapid synthesis of N-fused heterocycles. The key pre-aromatic spirocyclic intermediate initialized by the single electron transfer(SET) process of Togni’s reagent Ⅱ promoted by the tertiary phosphine resulted in an intriguing and alternative tactic for the cleavage of C–C bonds. By using inexpensive tertiary phosphine as the catalyst, this skeleton-reorganiz...     

Reactivity and antiproliferative activity of ferrocenyl-tamoxifen adducts with cyclodextrins against hormone-independent breast-cancer cell lines

Hydroxyferrocifen compounds are a new and promising class of ferrocifen-type breast-cancer drug candidates. They possess both endocrine-modulating properties and cytotoxic activity, which come from the tamoxifen skeleton and the presence of a ferrocene moiety, respectively. However, they suffer from reduced solubility in water, which presents a problem for their eventual therapeutic use. Herein, we examined the interactions of hydroxyferrocifen compounds with cyclodextrins (CDs) to evaluate whether or not their electron-transfer oxidation pathways were affected by their inclusion. It has been demonstrated that these inclusion complexes are soluble in pure water, which shows that CDs can be used to deliver these biologically active molecules. Therefore, a series of these compounds has been investigated by cyclic voltametry in various media in the presence of CDs (beta-CD and Me-beta-CD). In methanol, the hydroxyferrocifen compounds exhibited a weak interaction with the CD cavity. These interactions became stronger as the amount of added water increased. The complexation effect between the hydroxyferrocifen compounds and beta-CD was found to be stronger if the CD was partially methylated, which is probably due to hydrophobic effects between the cyclopentadienyl ring and/or the aromatic rings and the methoxy groups. Moreover, it appears that the structure of the hydroxyferrocifen compounds affects both their solubility and their complexation dynamics. Investigations in the presence of pyridine show that the base kinetically favors the dissociation of the ferrocifen-CD complex during the electron transfer step, but does not affect the follow-up reactivity of the electrogenerated ferrocenium cation, which leads eventually to the corresponding quinone methide, as reported in the absence of CD. Accordingly, the cytotoxicity of these beta-CD-encapsulated organometallic complexes in hormone-independent breast-cancer cells (MDA-MB231) were confirmed to be similar to those obtained in the absence of cyclodextrin.     

Synthesis and antiviral activity of new indole-based heterocycles

New 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine and 1,3-thiazole derivatives incorporating indole nucleus were prepared using 3-acetylindole as precursor and evaluated for their antiviral activity against herpes simplex type 1 (HSV-1).     

Synthesis and biological activity of bridgehead nitrogen heterocycles

The reaction of 3-(2,4-dichlorophenyl)-5-mercapto 1,2,4–1H-triazole with α-haloketones and with 1,2-dibromoethane leading to the formation of fused heterocycles were carried out and the orientation of cyclization was studied. The reaction of 3-(2,4-dichlorophenyl)-5-mercapto-4-amino-1,2,4-s-triazole with α-haloketones     

Synthesis and antiproliferative activity of RITA and its analogs

The synthesis of RITA and a variety of five-membered heterocyclic triads by the cyclocondensation of 1,4-bis(5-substituted-2-thienyl or 2-furyl)-1,3-butadiynes with water or Na₂S·9H₂O in the presence of KOH in DMSO is described. The study on the antiproliferative activities against K562, MCF-7, A549, and HCT116 tumor cells has revealed that some of the heterocyclic triads show higher antiproliferative activities than RITA, depending on the structures of substituents, the property of heteroatoms as well as their numbers.     

Improvement of cytotoxic activity of local anesthetics against human breast cancer cell line through the cyclodextrin complexes

Among the potent anticancer agents, Local Anesthetics (LA) have been found to be efficient against many different types of cancer cells. However, the major disadvantage associated with the use of LA its low systemic bioavailability when administered due to its poor aqueous solubility. Our present work concentrates on improving the bio-availability by complexing with cyclodextrin. We synthesized the inclusion complexion by co-precipitation method which is an efficient method among other and characterized the formulation of complex by UV and fluorescence studies. The in-vitro study of cytotoxicity against breast cancer cell line is performed. Our study shows the formation of the complex with 1:1 ratio and the result show both Benzocaine and Tetracaine inclusion complex has higher potential towards breast cancer cell than the free drug.     

Synthesis and antiproliferative activity of novel 4-substituted-phenoxy-benzamide derivatives

A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibitedmoderate efficacy in HT29 and MGC803 cell lines. Compound 10c showed promising inhibition of hedgehog (Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.     

New sorafenib derivatives: synthesis, antiproliferative activity against tumour cell lines and antimetabolic evaluation

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a-e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a-e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a-e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a-e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a-e (IC(50) = 1-4.3 μmol·L-1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.     

Synthesis and antiproliferative activity of novel A-homo-B-norsteroid thiadiazole derivatives

Using cholesterol as a starting material, two novel steroidal thiadiazole derivatives possessing a structure of A-homo lactam and a B-nor steroidal skeleton were designed and synthesized by six steps of reactions, and their antiproliferative activities were assayed against various cancer cell lines. The result shows that compound 7b displays an excellent selective inhibition to A-549 (human lung carcinoma) cancer cell lines with an IC₅₀ value of 8.0 μM.     

Synthesis of novel heterocycles with antimicrobial and surface activity

A new series of anionic surfactants with dual type of activity antimicrobial and surface activity have been synthesized by reaction of 4H‐3,1‐benzoxazinone 3 and quinazolinethione 10 with nitrogen nucleophiles and activated olefinic compounds. The compounds were evaluated for their surface activity as well as their antimicrobial and biodegradability properties.     

Synthesis, structure, spectroscopic properties, and antiproliferative activity in vitro of novel osmium(III) complexes with azole heterocycles

Reactions of (H 2azole) 2[OsCl 6], where Hazole = pyrazole, Hpz, ( 1), indazole, Hind, ( 2), imidazole, Him, ( 3) and benzimidazole, Hbzim, ( 4) with the corresponding azole heterocycle in 1:4 molar ratio in boiling isoamyl alcohol or hexanol-1 afforded novel water-soluble osmium(III) complexes of the type trans-[OsCl 2(Hazole) 4]Cl, where Hazole = Hpz ( 5a), Hind ( 6a), Him ( 7a), and Hbzim ( 9a) in 50-70% ( 5a, 7a, 9a) and 5% ( 6a) yields. The synthesis of 7a was accompanied by a concurrent reaction which led to minor formation (<4%) of cis-[OsCl 2(Him) 4]Cl ( 8). The complexes were characterized by elemental analysis, IR spectroscopy, UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. 5a, 7a, and 9a were found to possess remarkable antiproliferative activity in vitro against A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma) cells, which was compared with that of related ruthenium compounds trans-[RuCl 2(Hazole) 4]Cl, where Hazole = Hpz (5b), Hind (6b), Him (7b), and Hbzim (9b).     

In vitro evaluation of antiproliferative effect of ethyl gallate against human oral squamous carcinoma cell line KB

Although some polyphenols are known to possess anticancer activity against different cancer cell lines through induction of apoptosis, the mode of antiproliferative effect of ethyl gallate against human oral squamous carcinoma cell line KB was not studied until now. Therefore, the antiproliferative effect of ethyl gallate was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in comparison with the reference drug paclitaxel. Generation of reactive oxygen species, mitochondrial membrane potential loss, DNA damage and apoptosis were determined using 2,7-diacetyldichlorofluorescein fluorescence, uptake of rhodamine-123 by mitochondria, comet assay and acridine orange/ethidium bromide dual-dye staining method. Both ethyl gallate and paclitaxel exhibited cytotoxicity in a dose-dependent manner. The 50% inhibitory concentration for ethyl gallate was 30 and 20 μg/mL for paclitaxel. A volume of 50 μg/mL of ethyl gallate was found to be significantly effective (P < 0.05) in controlling the cancer cell proliferation leading to acute apoptosis.     

Synthesis and antiproliferative activity of new chlorin e6 glycoconjugates

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Synthesis and antiproliferative activity of 6,7-aryl/hetaryl coumarins

Two different series of novel analogs of 6,7-aryl/hetaryl coumarins 4a–4h and 8i–8l have been synthesized by using Suzuki–Miyara cross coupling reaction from 4-methyl-2-oxo-2H-chromen-7-yl trifluoro-methanesulfonate and 4-methyl-2-oxo-2H-chromen-6-yl trifluoromethanesulfonate in high yields (70–90%). All synthesized compounds were elucidated by means of IR, ¹H NMR, ¹³C NMR, and MS spectra. The synthesized compounds were tested for antiproliferative activity against different human cancer cell lines (SiHa, MDAMB-231, and PANC-1) and some of products demonstrated the distinctive effect.     

Synthesis and antiproliferative activity of combretastatin derivatives with adamantane fragment

Russian Chemical Bulletin - The work describes the synthesis of 2-adamantyl 7-[(2-{[(2E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enoyl]amino}ethyl)amino]-7-oxoheptanoate and...