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.     

Studies on photocrosslinkable-cum-flame retardant poly(benzylidene phosphoramide ester)s

Four series of photocrosslinkable-cum-flame retardant poly(benzylidene phosphoramide ester)s were synthesized from bis(4-hydroxy-3-methyoxybenzylidene) acetone, 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone, 2,6-bis(4-hydroxy-3- methoxybenzylidene)cyclohexanone and 2,7-bis(4-hydroxy-3-methoxybenzylidene) cycloheptanone with various arylphosphorodichloridates by interfacial polycondensation using a phase transfer catalyst. The resultant polymers were characterized by gpc, FTIR, ¹H, ¹³C and ³¹P-NMR spectroscopy. Thermal behavior of the polymers was evaluated by differential scanning calorimetry and thermogravimetry. Flame retardant properties were ascertained by Limiting Oxygen Index. The photocrosslinking ability of the polymers was studied by ultraviolet spectroscopy. The crosslinking proceeds via 2π + 2π cycloaddition reaction of the benzylidene groups. The rate of crosslinking decreases with increase in the size of cycloalkanone ring, while the thermal stability increases with increase in the size of the alkanone ring. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3285–3291, 1999     

金属钠—硫磺法合成聚苯硫醚

以金属钠和硫磺为原料,六磷胺作溶剂合成了聚苯硫醚。本工作表明,反应分为两个阶段,首先硫八元环断裂生成了由硫化钠和六磷胺组成的中间产物,中间产物再与对二氯苯反应生成聚苯硫醚。本工作还对钠与溶剂的反应及反应中微量水的影响作了研究。     

Crystal and Molecular Structure of N，N－Bis（2－chloroethyl）－N＇－isopropyl－N＂－phenyl Thioureido Phosphoramide

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手性磷酰胺类配体不对称催化串联反应合成手性3-取代苯酞化合物

以反式-1,2-二苯基乙二胺为原料合成了一系列磷酰胺类配体, 考察了该类配体在催化1,2-加成/内酯化串联反应合成手性3-取代苯酞化合物过程中的催化活性. 在最优条件下, 即在配体7d摩尔分数为20%时, 可以获得高达90%的收率及大于80% e.e.值的3-取代苯酞化合物; 该配体合成简单, 虽然作为催化剂使用量较大但较易回收再利用. 对反应机理进行了推测, 认为反应过程中形成的环状过渡态有助于提高反应的对映选择性.     

A Convenient Synthesis of Novel Phosphoramide Mustard Analogues of 2-Arylquinolone

A series of novel phosphoramide mustard analogues of 2-arylquinolones are synthesized through a convenient and facile phosphorylated reaction, and their structures are elucidated by NMR, IR, and HR MS. The amino acid esters and phosphoryl nitrogen mustard are linked to 2-arylquinolone to improve their undesirable physicochemical and biological properties.     

Synthesis of dimethylphosphorylamino diazo esters by a selective tandem Staudinger/Arbuzov rearrangement sequence of azido diazo esters with trimethylphosphite

γ-Azido-α-diazo-β-keto esters react selectively with trimethylphosphite by a tandem Staudinger/Arbuzov rearrangement sequence, furnishing γ-(dimethylphosphorylamino)-α-diazo-β-keto esters in good yield under mild conditions. Collected X-ray data for the novel diazo phosphoramides confirm the proposed chemoselectivity.     

31P NMR and HPLC Investigations of the Cyclophosphamide Metabolite,Phosphoramide Mustard

Abstract

Phosphoramide mustard (PM), a key active metabolite of the widely used anticancer drug cyclophosphamide (CP), can exist in several closely-related ionized, cyclized and substituted forms. We have developed a high pressure liquid chromatographic (HPLC) method for analysing serum concentrations of PM in order to relate these serum concentrations to toxicity and efficacy of treatment of CP. ³¹p NMR spectroscopy is used to verify the HPLC peak homology of the proposed PM peak.     

Synthesis of Novel Phosphoramide-Tegafur Derivatives Containing Aminopropylsilatrane

Abstract

A series of novel phosphoramide-tegafur derivatives containing γ-aminopropyl silatrane were synthesized via the condensation reactions of phosphoryl dichloride with N¹-(2-furanidyl)-N³-(hydroxyethyl)-5-fluorouracil, followed by condensation with γ-aminopropyl silatrane. The structures of the products were confirmed by ¹H NMR, ³¹P NMR, IR, MS, and elemental analysis. The results of preliminary bioassay showed that the new compounds had an inhibition effect against HCT-8 and Bel-7402 cell lines.     

Synthesis and Biological Activity of Cis 2-(6-Chloropyridine-3-yl)methylamino-4-substitutedphenyl-5,5-dimethyl-1,3,2-dioxaphosphinane 2-Oxides

A series of novel, asymmetric-cyclic phosphoramides containing substituted pyridine were synthesized via the condensation reactions of trans 2-chloro-4-substitutedphenyl-5, 5-dimethyl-1,3,2-dioxaphosphinane 2-oxide with 2-chloro-5-aminomethylpyridine or 3-aminomethylpyridine. The reactions show good stereoselectivity. Only the cis isomer from configuration inversion was obtained, which is the thermodynamic stable product. The structures of the products were characterized by ¹H NMR, ³¹P NMR, IR, MS, and elemental analysis. The configuration of the product was determined by X-ray diffraction analysis. The results of preliminary bioassay showed that the new compounds possess potential insecticidal and fungicidal activities.