In vitro antitumour activity of two isomeric cyclopalladiated compounds derived from benzoylbenzylidenimines

The DNA thermal stabilizing effect and antitumour properties of two diastereoisomeric cyclopalladiated compounds, Pd₂ [4-CH₃O–C₆H₄N?C(COC₆H₅)C₆H₄]₂(μ-OAc)₂ (I and II), derived from benzoylbenzylideneimines have been studied. The atropisomers containing two acetate-bridged PdL₂ units have a folded structure in boat form. The results show that both complexes interact with the DNA double helix but that compound II stabilizes the DNA more than compound I. It was also observed that the in vitro antiproliferative activity of compound II against colon (CX-1) and lung (LX-1) human tumour cells is higher than that of compound I. It is probable that the higher reactivity of compound II relative to compound I is due to the specific orientation of the benzoyl group with respect to the CO? CN chiral bond.     

具有实验抗癌活性的二烃基锡衍生物的研究进展

自从Crown报道了一些二烃基锡衍生物具有抗癌活性以来, 这一领域的研究引起了人们极大的兴越。许多二烃基锡衍生物被制备得到, 并且测定了它们在离体及活性情况下的抗癌活性。本文综述了二烃基锡衍生物抗癌活性的研究进展,包括化合物的结构类型, 抗癌作用机制以及利用QSAR方法对有机锡化合物的抗癌活性进行计算预测等。     

Synthesis and in vitro antitumour activities of lupeol derivatives

Nine lupeol derivatives were synthesised and assayed in vitro for their antitumour activities against three human tumour cells lines, A549, LAC and HepG2. Of lupeol derivaties, six were new compounds, and five compounds against A549 cells, four compounds against HepG2 cells and three compounds against LAC cells were effective in reducing viability, and the most promising compounds 5, 6 and 9 exhibited high activities against lung and liver cancer cells, even higher activities than those of adriamycin.     

Diorganotin 2-fluorocinnamates and 4-fluorophenylacetates: Synthesis,characterization and in vitro antitumour activity

The synthesis and characterization by spectroscopy of several new di-n-butyltin and diethyltin 2-fluorocinnamates and 4-fluorophenylacetates are described. In vitro tests on two human tumour cell lines, MCF-7, a mammary tumour, and WiDr, a colon carcinoma, showed that two of these compounds are more active than cisplatin. Other in vitro tests performed by the NCI, USA on a panel of human tumour cell line show that one of them, bis[di-n-butyl(2-fluorophenylacetato)tin] oxide, is characterized by statistically significant D, D_TGI and D sensitivities, but non-significant D_H and MGD_H selectivities, whereas the analogous 2-fluorocinnamate shows no such significant values.     

Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives

A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC₅₀ values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.     

Structure elucidation and antitumour activity of a new macrolactam produced by marine-derived actinomycete Micromonospora sp. FIM05328

Chemical investigation of a marine-derived actinomycete strain Micromonospora sp. FIM05328 isolated from a soil sample collected from the East China Sea, resulted in the discovery of a new 26-membered polyene macrolactam metabolite FW05328-1 (1), together with a known polyene with pyridone ring compound aurodox (2). The structures of compounds 1 and 2 were determined by the detailed analysis of 1D, 2D NMR and HR-TOF-MS data, along with literature data analysis. 1 and 2 exhibited excellent antiproliferative activities against KYSE30, KYSE180 and EC109 human tumour cell lines, but displayed no antibacterial activities against bacteria or fungi were tested.     

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.     

Toxicology and antitumour activity of ferrocenylamines and platinum derivatives

Toxicity, antitumour, platinum distribution, hepatotoxicity and histology data are presented for a series of ferrocenylamines: [(η‐C₅H₄(CH₂)_nNH₂)FeCp] (n = 0,1) ( 1 , 2 ); [(η‐C₅H₄CH₂NHPh)FeCp] ( 3 ); [(η‐C₅H₄CH₂NMe₂)FeCp] ( 4 ); {[η‐C₅H₄CH(Me)NMe₂]FeCp} ( 5 ); [η‐C₅H₄CH₂NMe₂)₂Fe] ( 6 ); {[1,2η‐C₅H₃(CHMeNMe₂)(PPh₂)]FeCp} ( 7 ); {[1,2η‐C₅H₃(CHMeNMe₂)(PPh₂)]Fe[η‐C₅H₄PPh₂]} ( 8 ); and their complexes cis‐PtCl₂L₂ ( 9 ); trans ‐ Pt(L)(dmso)X₂ ( 10 ); [σ ‐ (L)Pt(dmso)X] ( 11 , 12 ) {σ‐(L)[Pt(dmso)X]₂} ( 13 ); [σ‐(L)PtP(OPh)₃Cl] ( 14 ) (L = ferrocenylamine). The toxicity order is 1 – 3 ≫ 4 – 8 for the ferrocenylamines; the lower toxicity of tertiary amines may be due to protonation in vivo. Pt(II) complexes all show increased toxicity over the ligand. Liver, not kidney, damage is the norm from i.p. injection of 1 – 14 and detailed platinum distribution, blood serum and histology studies with 9 and 11 show that the platinum distribution does not correlate with liver dysfunction. Complexes 9 – 14 , but not 1 – 8 , were active against P‐388 mouse leukaemia tumour and cisplatin‐resistant sarcoma, but inactive against L‐1210 mouse leukaemia and B‐16 melanoma. Copyright © 1999 John Wiley & Sons, Ltd.     

Crystal structure and in vitro antitumour activity of dibutylbis(5-chloro-2-hydroxybenzoato)tin(IV)

The crystal structure of the title compound, [nBu₂Sn(5-Cl-2-OH-C₆H₃CO₂)₂], shows that in the monomeric species the six-coordinate Sn atom exists in a skew trapezoidal bipyramidal geometry in which the four O donor atoms, derived from two asymmetrically chelating carboxylate ligands, define the basal plane and the n-butyl substituents lie over the weaker Sn? O interactions defining a C? Sn? C angle of 147.6(2)°. An unusual feature of the structure is the presence of both intra- and inter-molecular hydrogen bonding contacts which serve to stabilize the structure. The in vitro antitumour activity of this compound against mammary and colon carcinoma cell lines is also reported.     

Synthesis,characterization and in vitro antitumour activity of di‐ and tri‐organotin derivatives of fenbufen

The di‐ and tri‐organotin derivatives of fenbufen (4‐(4‐biphenyl)‐4‐oxobutyric acid), [{(n‐C₄H₉)₂Sn(OCOCH₂CH₂COC₆H₄C₆H₅‐4)}₂O]₂ ( 1 ) and R₃SnOCOCH₂CH₂COC₆H₄C₆H₅‐4 (R?C₆H₅, 2 ; c‐C₆H₁₁, 3 ; C₆H₅C(CH₃)₂CH₂, 4 ), have been prepared and characterized by means of elemental analysis, IR and NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopies. The crystal structure of 1 , bis[4‐(4‐biphenyl)‐4‐oxobutyrato]tetra‐n‐butyldistannoxane, has been determined and it is a centrosymmetric dimer with two distinct types of carboxylate moieties and tin atoms with distorted trigonal bipyramidal geometries. The in vitro antitumour activity of 1 and 2 against two human tumour cell lines was found to be higher than that for cis‐platin used clinically. Copyright © 2005 John Wiley & Sons, Ltd.     

Neurotropic activity of organogermanium compounds

Neurotropic activity of several classes of organogermanium compounds (namely germatranes, germanols, germsesquioxanes, germyladamantanes, germylamides, germylimides and germylsubstituted amines, imines and hydroxamic acids) and their synthesis are reviewed.     

Organotin gibberellates: Synthesis,spectroscopic characterization and antitumour activity

The synthesis and characterization of di-n-butyl-, tri-n-butyl- and triphenyltin gibberellates are reported. Their antitumour activities in vitro against a panel of seven human tumour cell lines are given and compared with those of drugs used clinically. Copyright © 1998 John Wiley & Sons, Ltd.     

Synthesis,characterization and in vitro antitumour properties of complexes of bis(alkoxycarbonylmethyl)tin dibromides with bidentate nitrogen ligands

The synthesis and characterization of 10 new bis(;alkoxycarbonylmethyl)tin dibromides and of 14 of their complexes with bidentate nitrogen ligands (;bipyridyl, 1,10-phenanthroline and 5-nitro-1, 10-phenanthroline) are described. Their proton NMR spectra are discussed. Their in vitro antitumour activity against two human cancer cell lines, MCF-7 and WiDr, is low compared to antitumour drugs used clinically.     

Tetraethylammonium (diorgano)halogeno-(2, 6-pyridinedicarboxylato)stannates: Synthesis,characterization and in vitro antitumour activity

The synthesis and characterization of tetraethylammonium (diorgano)halogeno(2, 6-pyridinedicarboxylato)stannates are described. The solution structures of these complexes in CDCl₃ and DMSO are discussed on the basis of ¹¹⁹Sn and ¹⁹F NMR data. Their in vitro antitumour activities against two human tumour cell lines, MCF-7 and WiDr, are presented.     

Di‐ and tri‐organotin derivatives of 3S,4S‐3‐[(R)‐1‐(tert‐butyl‐dimethylsilyloxy)ethyl]‐4‐[(R)‐1‐carboxyethyl]‐2‐azetidinone: synthesis,characterization and in vitro antitumour activity

Di‐n‐butyl‐, triphenyl and tri‐n‐butyltin derivatives of 3 S, 4 S ‐3‐[( R )‐1‐(tert‐butyldimethyl‐­<?tw=103.5%>silyloxy)ethyl‐4‐[( R )‐1‐carboxyethyl]‐2‐azetidi<?tw>‐­none were synthesized and characterized. Their antitumour activity was screened against seven tumoural cell lines of human origin. Copyright © 1999 John Wiley & Sons, Ltd.     

Silyl modification of biologically active compounds. 12. Silyl group as true incentive to antitumour and antibacterial action of choline and colamine analogues

A series of triorganylsilyl(β‐dialkylaminoethoxy)silanes was prepared and characterized by elemental analysis, ¹H, ¹³C, ²⁹Si NMR and mass spectroscopy. Comparative study of ²⁹Si resonance of newly synthesized compounds showed correlation between its value and substituent nature at the silicon atom, and is shifted upfield for β‐triorganyl(N,N‐dialkylaminoethoxy)silanes in comparison with corresponding methiodides, revealing weak N^…Si interaction for proper silanes. In vitro antitumour and antimicrobial properties were investigated. The biological activity data exhibited a marked enhancement of inhibitory activity on trialkylsilylation against tumour cell lines and all the test bacterial/fungal strains. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis,characterization, X‐ray crystal structure and in vitro antitumour activity of sodium bis(2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylato)triphenylstannate

Sodium bis[2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylato]triphenylstannate, [(CH₃OCH₂CH₂OCH₂CH₂OCH₂CH₂)‐1,2‐C₂B₁₀H₁₀‐9‐COO)₂SnPh₃]^? Na⁺, compound 1, was synthesized by the 1:1 condensation of triphenyltin(IV) hydroxide with 2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylic acid and crystallized in the presence of sodium bicarbonate. Its structure was determined by spectroscopy, elemental analysis and X‐ray diffraction. The structure of 1 consists of trigonal bipyramidal [Sn(Ph)₃(L)₂]^? anions and Na⁺ cations coordinated by oxygen atoms of polyoxaalkyl chains of different stannate anions, forming cation–anion chains elongated along the c axis. Compound 1 is significantly more active in vitro against seven tumour cell lines of human origin than 5‐fluorouracil, cis‐platin, carboplatin, and previously reported organotin carboranecarboxylates, but is less active than organotin polyoxaalkylcarboxylates. Copyright © 2004 John Wiley & Sons, Ltd.     

Comparative study of the biological activity of organosilicon and organogermanium compounds

The literature data and the results of our own investigations on the comparative study of the biological activity of isostructural organogermanium and organosilicon compounds have been summarized. It has been shown that the series of organogermanium and organosilicon compounds is more active than the carbon analogues, the majority of organogermanium compounds are less toxic than the sila analogues, the biological activity of the compounds under study appears to be similar but can dramatically differ in the degree of activity, and, moreover, in some particular cases sila and germa analogues exhibit the opposite biological effects.     

Interpretation of the antitumour activity of some diacridines

Relationships are formulated in an attempt to explain the variation in the antitumour activity and toxicity of a series of diacridines. Three types of conformation are considered, these being relevant to the three types of double intercalation of DNA. The CNDO /2 method, with the incorporation of symmetry adapted orbitals, is used to obtain electron reactivity indices. Significant correlations are presented between the biological activities and the electronic and steric indices employed.