29549-98-2Relevant articles and documents
Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer
Tokay, Esra,Güng?r, Tu?ba,Hac?o?lu, Nelin,?nder, Ferah C?mert,Gülhan, ünzile Güven,Tok, Tu?ba Ta?k?n,?elik, Ayhan,Ay, Mehmet,K??kar, Feray
, (2019/12/24)
Prodrugs for targeted tumor therapies have been extensively studied in recent years due to not only maximising therapeutic effects on tumor cells but also reducing or eliminating serious side effects on healthy cells. This strategy uses prodrugs which are safe for normal cells and form toxic metabolites (drugs) after selective reduction by enzymes in tumor tissues. In this study, prodrug candidates (1-36) containing nitro were designed, synthesized and characterized within the scope of chemical experiments. Drug-likeness properties of prodrug candidates were analyzed using DS 2018 to investigate undesired toxicity effects. In vitro cytotoxic effects of prodrug canditates were performed with MTT assay for human hepatoma cells (Hep3B) and prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) as healthy control. Non-toxic compounds (3, 5, 7, 10, 12, 15, 17, 19 and 21–23), and also compounds (1, 2, 5, 6, 9, 11, 14, 16, 20 and 24) which had low toxic effects, were selected to examine their suitability as prodrug canditates. The reduction profiles and kinetic studies of prodrug/Ssap-NtrB combinations were performed with biochemical analyses. Then, selected prodrug/Ssap-NtrB combinations were applied to prostate cancer cells to determine toxicity. The results of theoretical, in vitro cytotoxic and biochemical studies suggest 14/Ssap-NtrB, 22/Ssap-NtrB and 24/Ssap-NtrB may be potential prodrug/enzyme combinations for nitroreductase (Ntr)-based prostate cancer therapy.
Chromatographic approach to the measurement of the interstrand distance for some chiral bonded phases
Pirkle, William H.,Readnour, Robin S.
, p. 16 - 20 (2007/10/02)
A series of homologous N,N′-bis(2,4-dinitrophenyl)-α,ω-diaminoalkanes (bis-DNP's) was chromatographed at various temperatures on π-basic chiral stationary phases derived from N-(2-naphthyl)alanine in order to determine the enthalpy and entropy of adsorption. The number of methylene groups in the bis-DNP's influences the ability of the terminal π-acidic groups to interact simultaneously with neighboring strands of stationary phase, a process termed "bridging". When the number of methylene groups is optimal for bridging, the enthalpy of adsorption is most exothermic. The length of the bis-derivative required for optimal bridging is related to the interstrand distance. Optimal bridging occurs for the bis-DNP's having five methylene groups regardless of the extent of surface coverage of the silica for the surface coverage range investigated. This suggests that the strands are not randomly spaced on the silica, with interstrand distance being influenced only by surface coverage, but are instead clustered, the clusters having similar distributions of interstrand distances. Adsorption is more exothermic for phases of high surface coverages than for low. If Interstrand spacing is independent of surface coverage but surface coverage affects the enthalpy of adsorption, then surface coverage must influence the cluster size, which then influences the average extent of solvation of a strand of bonded phase.
Chemotherapeutically active nitro compounds. I. Nitroanilines
Winkelmann,Raether,Dittmar,et al.
, p. 681 - 708 (2007/10/05)
More than 200 nitro compounds, most of them nitroaniline derivatives substituted with one or more radicals having a basic reaction, were prepared and investigated as to their therapeutic activity against bacteria, fungi, protozoa, helminths, viruses and tumors. Several mono nitrobenzenes with a radical having a basic reaction showed a weak in vitro activity against gram positive bacteria and against Crocker's sarcoma 180; they also showed systemic activity against nematodes (Aspiculuris tetraptera) and viruses. The majority of therapeutically active compounds with pronounced in vitro activity against Trichomonas fetus, Entamoeba histolytica, Schistosoma mansoni, cestodes, nematodes (Ancylostoma caninum), viruses (influenza, MHV, SAV and EMC) and various types of carcinoma (Ehrlich's carcinoma, leukemia 1210, Crocker's sarcoma 180) were dinitrobenzene derivatives with one radical having a basic reaction and electropositive groups or unreactive or reactive chlorine atom, and di nitrobenzene with two equal or two different radicals having a basic reaction. Compound No. 70 revealed a marked in vitro activity against fungi (Trichophyton; Microsporum, Candida albicans). Other nitro compounds such as bis mono and bis dinitrobenzene derivatives likewise showed a systemic action against E. histolytica, viruses and, in particular, carcinoma (Crocker's sarcoma 180, Ridgway's osteosarcoma). Oxygen and sulfur analogue compounds as well as compounds produced by reduction also possessed a distinct activity against E. histolytica and viruses. On the basis of the present results, the dinitrobenzenes substituted with two radicals having a basic reaction include a number which have in common a recognizable structure/activity relationship in respect to E. histolytica, Schistosoma mansoni and different types of viruses. The activity against viruses in this class of compounds is probably due to an increased interferon production in the host animal. Whether the mechanism of action is the same against E. histolytica or Schistosoma mansoni has not been determined so far. A tumorigenic effect was observed mainly in those di nitrobenzenes which are classed as alkylating compounds. Because of the small chemotherapeutic index, the trials were not continued with the most effective compounds mentioned.
