Synthesis and cytotoxicity of pentacyclic triterpenes-aniline nitrogen mustard derivatives

To discover novel nitrogen mustards, the reported mustard pharmacophore was combined with natural pentacyclic triterpenes, which are characterized with pharmacological and structural diversity. Thus, six conjugates were synthesized with 1,2,3-triazole linking N,N-bis (2-chloroethyl)-1,4-phenylenediamine and oleanolic acid, ursolic acid, or glycyrrhetinic acid, and their biological activity was evaluated against tumor cell lines HeLa, BGC-823, BEL-7404, and NCI-H460 using the MTT assay. As a result, these conjugates showed some selective cytotoxicity to NCI-H460, though all their activity potency was moderate or weak in the four cell lines.     

Synthesis,characterization and antitumor activity of benzalde- hyde nitrogen mustard picolinoyl hydrazone complexes

CuII, NiII, CoII, ZnII and CdII complexes of picolinamido-4-bis(2-chloroethyl)aminobenzaldimine (PBAB) have been synthesized and characterized by elemental analysis, conductivity, i.r. u.v.-vis. and e.p.r. spectra. The results suggest a square planar structure for the CuII complex, a tetrahedral geometry for the ZnII and CdII complexes and an octahedral structure for the CoII and NiII complexes. The complexes have been screened for antitumor activity against SMMC-7721 human liver cancer cell line; all of them exhibit biological activity at high concentrations for the cell line studied and a synergic effect between CuII and PBAB is evident.     

Synthesis and characterization of glycosylated nitrogen mustard derivatives and their interaction with bovine serum albumin

To improve the specificity of nitrogen mustards towards tumor cells, glucose-nitrogen mustard, fructose-nitrogen mustard, and lactose-nitrogen mustard were prepared as three novel glycosylated nitrogen mustard derivatives by esterification of bis(2-chloroethyl)carbamic chloride (BCC) with glucose, fructose, and lactose, respectively. BCC was synthesized from bis(2-chloroethyl)amine hydrochloride and triphosgene. The topic products were characterized by infrared (IR) and mass spectrometry (MS), and their interaction with bovine serum albumin was investigated by measuring fluorescence spectra in tris(hydroxymethyl)aminomethane hydrochloride (Tris–HCl) buffer solution at physiological conditions.     

Synthesis,cytotoxicity, topoisomerase I inhibition and molecular docking of novel phosphoramide mustard sophoridinic acid analogues

A series of novel phosphoramide mustard sophoridinic acid analogues, consisting of nitrogen mustard group and sophoridinic acid scaffold, have been designed, synthesized and evaluated for their topoisomerase inhibitory activity as well as cytotoxicity against six tumor cell lines (SMMC‐7721, LoVo, MCF‐7, K562, S180 and H22) and a normal cell line (L929). Among the compounds tested, five were found to be potent inhibitors and exhibited potent cytotoxicity against S180 and H22 cell lines with IC₅₀ values of 1–4 μM. Further mechanistic studies showed that this class of compounds acted as novel topoisomerase I (Topo I) catalytic inhibitors by preventing the binding of Topo I to DNA and inhibiting the cleavage of DNA, and molecular docking studies revealed that the binding energy for these compounds was comparable to that for classic Topo I inhibitors CPT and HCPT, indicating that the compounds have an interaction with DNA and Topo I.     

Synthesis and cytotoxicity of indolopyrrolemaleimides

A series of indolopyrrolemaleimides have been synthesized and evaluated for their cytotoxicity in vitro against human leukemia cell line and four human solid cancer cell lines. Some of the compounds showed high or mediate activity against the lines. 6dc is the most promising compound among them. The inhibition toward topoisomerase I was also studied.     

Synthesis, characterisation and cytotoxicity of polyoxometalate/carboxymethyl chitosan nanocomposites

Chitosan and its derivates continue to attract considerable research interest as effective drug carriers with good biocompatibility and high cellular uptake rates. We used these versatile features to tap the considerable biomedical potential of polyoxometalates (POMs) through their encapsulation into a carboxymethyl chitosan (CMC) matrix. The nanocapsules were prepared by ionic gelification with Ca(2+); their size distribution ranges from 60 to 150 nm. Because [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10-) is well known for its manifold properties, such as antiviral activity, it was selected as a model POM. The resulting composites were characterised with a wide range of analytical methods, which pointed to quantitative encapsulation of intact POMs within the CMC matrix. We studied the biocompatibility of the POM/CMC nanocomposites on HeLa cells through MTT and proliferation assays. Even after prolonged incubation times at high concentrations, the composites did not display cytotoxicity, thereby drastically reducing the side effects of the pristine POMs. This opens up new avenues for designing novel inorganic drug prototypes from bioactive POMs.     

Synthesis of a triterpene-spermidine conjugate

Three synthetic approaches to triterpene-spermidine conjugate coupled at the C³ atom have been tested. The best yield was obtained by reductive amination of betulonic acid methyl ester with spermidine.     

Synthesis and properties of a surfactant-cyclodextrin conjugate

A surfactant-cyclodextrin conjugate. in which an ion-terminated chain is attached to each of the seven cyclodextrin sugars, has been synthesized and examined by a variety of physical methods.     

Synthesis and properties of PI polyamide-SAHA conjugate

We have designed and synthesized new types of pyrrole (P)-imidazole (I) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation.     

Synthesis of 2-iminothiazoline derivatives by sequential conjugate addition/annulation/ring-opening reactions

1,2-Diaza-1,3-butadienes reacted with rhodanine affording 2-(mercaptoacetyl)iminothiazoline derivatives through conjugate addition/annulation/ring-opening/oxidative dimerization. The hypothesized ring-closure and ring-opening mechanism was supported by X-ray crystal structure analysis of a compound obtained by reaction of the same reagents with a chiral 1,3-oxazolidine-2-thione derivative.     

Anionic carbonato and oxalato cobalt(III) nitrogen mustard complexes

Synthetic approaches to cobalt(III) complexes [Co(L)(L')2] containing the bidentate dialkylating nitrogen mustard N,N-bis(2-chloroethyl)-1,2-ethanediamine (L = dce) together with anionic ancilliary ligands (L') which are either carbonato (CO3(2-)), oxalato (ox2-), bis(2-hydroxyethyl)dithiocarbamato (bhedtc-), 2-pyridine carboxylato (pico-) or 2-pyrazine carboxylato (pyzc-) were investigated. Synthetic routes were developed using the related amines N,N-diethyl-1,2-ethanediamine (dee) and 1,2-ethanediamine (en). The complexes [Co(CO3)2(L)]- (L = dee 1, dce 2), [Co(ox)2(L)]- (L = dee 3, dce 4), [Co(bhedtc)2(dee)]+ 5, [Co(bhedtc)2(en)]+ 6, mer-[Co(pico)3], mer-[Co(pyzc)]3 7 and [Co(pico)2(dee)]+ 8 were prepared and were characterised by IR, UV-Vis, 1H and 13C[1H] NMR spectroscopy, mass spectrometry and cyclic voltammetry. [Co(bhedtc)2(en)]BPh4 6b and trans(O)-[Co(pico)2(dee)]ClO4 8 were characterised by X-ray crystallography. In vitro biological tests were carried out on complexes 1-4 in order to assess the degree to which coordination of the mustard to cobalt attenuated its cytotoxicity, and the differential toxicity in air vs. nitrogen.     

沙利多胺与叶酸偶联物的合成研究

本文报道了沙利多胺与叶酸偶联物的合成方法。以廉价易得的邻苯二甲酸酐和谷氨酰胺为原料通过酰化、环合反应得到沙利多胺,沙利多胺与37%甲醛溶液通过羟甲基化反应得到N-羟甲基沙利多胺,再与N-羟基琥珀酰亚胺(NHS)活化的叶酸通过偶联反应得到目标化合物。合成的关键中间体和目标化合物的物性与文献一致,其结构经核磁共振氢谱确认。     

Synthesis of a silk-inspired peptide-oligothiophene conjugate

The first example of an oligothiophene-peptide conjugate, which was obtained by solid-phase acylation of a resin-bound silk-inspired oligopeptide sequence with a carboxylic acid functionalized regioregular tetra(3-hexylthiophene) derivative, is reported.     

Synthesis and cytotoxicity of novel podophyllotoxin derivatives

In order to find novel synthetic antitumor agents with superior cytotoxicity 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 N-substituted 5-methylindol-3- yl-glyoxyl chlorides and tested against K562 and K562/A02 using SRB methods in vitro,KB and KBV using MTT methods in vitro.     

Synthesis of aziridinomitosenes through base-catalyzed conjugate addition

Synthesis of an aziridinomitosene core structure that relies on a facile tertiary-amine base-catalyzed azide conjugate addition is reported. Straightforward derivatization of the conjugate addition product affords the desired mitomycin ring system. Initial catalyst screens have identified peptides that afford the product with modest enantioselectivities.     

Synthesis of a water-soluble triazole-linked cavitand-guanosine conjugate

A convergent synthesis of a water-soluble cavitand bearing four triazole-linked guanosines was achieved. The critical coupling reaction entailed a copper-catalysed azide-alkyne cycloaddition between 5′-azido-5′-deoxyguanosine and a cavitand template functionalized with propargyl ether rim groups and water-solubilizing phosphate pendant groups.     

Synthesis of deuterium labeled ezetimibe and its glucuronide conjugate

Journal of Radioanalytical and Nuclear Chemistry - Ezetimibe is an effective cholesterol absorption inhibitor approved for the combined treatment with statins to reduce LDL-C level. Ezetimibe...     

Synthesis and spectral study of a novel distamycin conjugate

The ¹H and ¹³C NMR resonances for a novel distamycin conjugate, 3‐[1‐methyl‐4‐[1‐methyl‐4‐[1‐methyl‐4‐[N¹‐[5‐methyl‐2,4(1H,3H)pyrimidinedione]acetylamino]pyrrole‐2‐carboxamido]pyrrole‐2‐carboxamido]pyrrole‐2‐carboxamido]propionamidine hydrochloride ( 1 ), were assigned, using the concerted application of one‐ and two‐dimensional NMR techniques including nuclear Overhauser effect difference, DEPT, HMQC and HMBC experiments. Copyright © 2003 John Wiley & Sons, Ltd.